text:
Why is the 3'UTR AES of the Pfizer/BioNTech vaccine preceded by a CUC GAG?
According to the WHO submission and one of the preprints from BioNTech/Pfizer, the 3'UTR of their Covid-19 vaccine's mRNA is the combo of the AES and mtRNR1 sequences, which (in the preprint) BioNTech cites to a paper on library screening of 3'UTRs that achieve high mRNA stability etc.
But as far as as I can tell, BioNTech added a "CUC GAG" between the (doubled) stop codon and the beginning of the AES as it's given in Supplementary Table 3 of the library paper cited, i.e. the actual AES starts with CUG GUA CUG, or more precisely using the global Ψ substitution as given in the WHO submission, the sequence starting with the stop codon(s) is:

ΨGA ΨGA CΨC GAG CΨG GΨA CΨG CAΨ GCA

So, what's the point of the bolded "glue" CUC GAG?

There is also this part at the end ACCCTGGAGCTAGCAAAAAAAAA...

@reuns: FWTW, they did not add any glue in between the AES and mtRNR1 sequences (which form the "double UTR" as they call it)  GACACCΨCC CAAGCACGC.

The final part of mtRNR1 has something appended though compared to the library paper (it ends with AGCCACACC in supp. table 3), but in the WHO doc it has AGC CAC ACC CΨG GAG CΨA GCA AAAAA

Looking at the library paper more closely they, speak of a "motive core area" and "flanking areas" so these might be the latter, and were perhaps not interesting enough to publish at the time.

I think your linked article explains perfectly how they came with the 3'UTR. I am not too worried that there is a 15+6 nucleotide difference with the vaccine as they didn't show exactly how they are mixing two 3'UTR. If you really really want to know you can try asking directly to Kariko on twitter.


text:
Are there other examples besides wasps' polydnaviruses in which a parasitic species introduces an immunosuppressant virus in the parasite's host?
An interesting form of mutualism:

Parasitoid wasps serve as hosts for the virus, and Lepidoptera serve as hosts for these wasps. The female wasp injects one or more eggs into its host along with a quantity of virus. The virus and wasp are in a mutualistic symbiotic relationship: expression of viral genes prevents the wasp's host's immune system from killing the wasp's injected egg [...]

I'm guessing suppressing the immune system of the host is done by other parasitic species in various ways, but are there any other examples in which a virus is "used" for this purpose?

Not exactly the same, but Toxoplasmosis leading to loss of aversion of mice towards cats is a behavioral suppression: https://www.nature.com/news/parasite-makes-mice-lose-fear-of-cats-permanently-1.13777#/b1

Summarizes more related-but-not-quite-the-same systems: https://academic.oup.com/bioscience/article/49/4/311/228949

source: Stack Exchange

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

sort: votes


text:
Is the receptor of SARS-CoV-like viruses in bats still unknown?
A fairly detailed 2012 review (Whittaker et al.) on the Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein noted that

SARS-CoV-like viruses have been isolated in bats. In this case, entry does not occur via ACE2 and their receptor(s) is/are unknown; however, replacement of the amino acid sequence found between residues 323 and 505 with the corresponding sequence of the SARS-CoV RBD is sufficient to allow human ACE2 receptor usage [46].

Is the actual (bat) receptor that allows SARS-CoV-like viruses to replicate in bats still unknown?

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


text:
Minimum size for a peptide/protein to be immunogenic in human?
What is the minimum size for an (injected) peptide/protein to cause immunogenic response in human?
A reference is very helpful, as well.
Thanks in advance

Possible duplicate of http://biology.stackexchange.com/q/7905/3340

@WYSIWYG Looks a bit like, but I think this question goes further, especially since the other question and the answer focus more on metal conjugates.

There's a few limiting factors including how proteins are presented that constrains the actual size needed to get peptide presentation. These depend largely on the MHC molecules (HLA in humans). The binding groove in MHC-I actually limits the size of peptides it can load to 8-10 amino acids, 9 being the most common. This is because "pockets" at either end of the binding groove are said to actually grasp the peptide, and it doesn't allow for much longer sequences. MHC-II lacks these grasping pockets, and so it can bind much longer sequences (Figure 1). MHC-II typically binds sequences of 13-25 amino acids.

Figure 1. Difference between the MHC-I and II binding groove.
There are also a given number of requisite anchor residues that complement the binding pocket of the MHC binding groove that mostly display a particular character at the given position (normally polar at a given position, etc.) (Figure 2).

Figure 2. Just a sampling of possibilities across HLA isoforms.
All information and figures courtesy of Parham "The Immune System," 4th ED.
If the presented peptide has met the prerequisities and has been identified by a leukocyte, in theory it should produce an immune response. I think these are some good considerations to make when you're thinking about how small can a peptide be. I'm assuming here that MHC-II would be handling your injected protein through an extracellular pathway (I can't know for sure), and so the smallest literature MHC-II peptide range I've ever seen is 11 amino acids on the low side. There are a number of computational studies out there that attempt to predict MHC affinity, but it's problematic due to the range of sizes MHC-II may bind and there is variability among the binding cores that contain the anchor amino acids.

Can small peptides can act like haptens? Can you add some details on this, if you know? MHC peptide length may not really mean the smallest immunogenic size. In fact, very recently I heard someone talk about an antibody against a tripeptide for doing immunoprecipitation. I asked the speaker if he really meant an antibody against a general tripeptide epitope and he confirmed so. I forgot which tripeptide it was but it was supposedly generated after a tryptic digest of the ubiquitin tag (so possibly the RGG tripeptide). Even the well known FLAG-tag (DYKDDDDK) is an octapeptide.

I will attempt to find the resources, but from what I understood about tripeptide antigens is they're considered non-immunogenic as they typically can't elicit a primary immune response, whereas they're perfectly capable of somehow activating a DTH reaction. So in that sense they would act more like a nucleic acid or lipid in that they're largely non-immunogenic haptens. I'm unsure if that would end up out-of-scope for OPs question about immunogenic peptides.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/


text:
What’s so remarkable about position effect variegation?
I am reading Albert et. al’s Molecular Biology of the Cell and at one point the authors discuss the idea of “position effect variegation.” They mention that through events of DNA relocation, it’s possible for portions of echromatic DNA to become heterochromatic by being positioned next to heterochromatic DNA. They stress that “remarkably,” this heterochromatic state of DNA often gets inherited by the cell progeny. This phenomenon of inheritance is what they call, or I guess is called, position effect variegation. I don’t quite see what’s so “remarkable” about this, which is making me wonder if there’s something I’m underappreciating or misunderstanding. In particular, if the underlying DNA structure is changing, then wouldn’t we expect the progeny to inherit these epigenetic changes? Why is it so remarkable?
Here's the actual quote from the book:

In chromosome breakage-and-rejoining events of the sort just
described, the zone of silencing, where euchromatin is converted to a
heterochromatic state, spreads for different distances in
different cells in the fly embryo. Remarkably,
these differences then are perpetuated for the rest of the
animal’s life: in each cell, once the heterochromatic condition is
established on a piece of chromatin, it tends to be stably inherited
by all of that cell’s progeny (Figure 4–31). This remarkable
phenomenon, called position effect variegation, was first recognized
through a detailed genetic analysis of the mottled loss of red pigment
in the fly eye

and later on:

But in at least some cases, the covalent modifications on nucleosomes
can persist  long after the transcription regulator proteins that
first induced them have disappeared, thereby providing the cell with a
memory of its developmental history. Most remarkably, as in the
related phenomenon of position effect variegation discussed above,
this memory can be transmitted from one cell generation to the next.

Re:

In particular, if the underlying DNA structure is changing, then
wouldn’t we expect the progeny to inherit these epigenetic changes?
Why is it so remarkable?

Given the context of the quote, the "variegation" part of the phrase refers to gene expression sometimes being turned off by influence of newly-nearby heterochromatin. The extent to which this suppression of expression extends into the euchromatic region from the adjacent heterochromatin varies from cell to cell, but once established is stably inherited through further divisions of that cell. It is unknown what molecular mechanisms initiate and maintain the suppression of expression in the formerly euchromatic genes.
Since we do not fully understand the molecular nature of what is required to initiate and maintain heterochromatin, especially in a section of DNA that was formerly euchromatin and so presumably does not contain any global "make me heterochromatin" sequence signals, the "remarkable" likely means "we don't yet understand the details" -- it's like magic.

I added the quote

There's no evidence the actual DNA is changing. The molecular mechanism of this "creeping heterochromatinization" is unknown as far as I know. I think we would guess it might have to do with nucleosome positioning or state.


text:
Identify this insect seen in a rural area in North India
During my stay at a village in Haryana, India, I noticed many of these grey-brown insects in my room. They spend most of their time crawling but occasionally fly too (for short distances—one metre to a few metres). Here are some photographs—the spacing between the ruled lines is about 7 mm:

I am curious to know what species they are. Any help would be appreciated.


text:
tetrads in meiosis are held together by what
This is from SAT subject biology test practice question. The answer it gave me was both chiasmata and centromeres. I can understand they are held by chiasmata but why also centromeres? I looked it up, I didn't find anywhere mentioned that they are held by centromeres also, only synaptonemal complex and chiasmata.
tetrads are truly held by spindle fibers on centromeres too, but isn't the question asking what hold them together? Even without spindle fibers, they can still be held by chiasmata I guess.

A recombinase only active during meiosis - Dmc1 and a general recombinase Rad51 coat the single-stranded DNA to form nucleoprotein filaments. These filaments hold the homologs together at the chiasma, the point of attachment during crossing over.

It may help to think of the question in this way. Within a tetrad (that is 2 bivalents) there are 4 strands of DNA (really chromatin). Only the 2 inside strands are held together by the chiasmata. The outside strands are attached to the tetrad by it's centromere. Each pair of sister chromosomes are held in place at the centromeres during meiosis I. The sister chromosomes segregate together because the attached microtubules are oriented towards the same pole. They separate at the centromere at anaphase II to form the haploid gamete.

all_licenses: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/3.0/


text:
Thoughts precede neuron firing or vise-verse?
I am at the verge of submitting a paper on 'scientific explanation of reality' to an international philosophy body. First submitted draft was returned by the evaluation expert, asking me to re-submit it, after re-checking the validity of my  assertion that 'science (biology) believes that neuron firing always precedes thought'. Can any one provide answer on biology's clear stand on above question ?

how do you define "thought" biologically?

see the "materialism" philosophy debate. biologists are more agnostic on this, a position not really required for biological work. maybe a better fit on [philosophy.se] or [cogsci.se]. there is possibly some data from neurobiology specifically brain imaging studies that does impinge on the question.

I would suggest doing reading on corollary discharge to answer part of your question.

i'd be surprised if you could find a neuro-scientist who didn't go at least this far.

this should be on the neuroscience stack. Voting to close until you migrate it.

@John — the question is too old to migrate, and the original poster hasn't been seen in the last seven years.

I think the only way to interpret these kinds of questions biologically is to assume that "thought" means "the perception of a thought occurring." The perception of a thought, like all perception, arises from neuronal firing.
The interesting biological (rather than philosophical) questions arise when we look at the relationship between the neural firing that gives rise to the perception of intent to act and neural firing that carries out the "intended" actions.
This paper is relevant. The authors are trying to argue that the initiation of a motor action comes before the perception of intent for that action. I'm not a cognitive neuroscience person, though, so I'm not very familiar with their techniques and personally have a hard time determining if they draw valid conclusions.

I didn't read the paper that you linked, but the reaction time literature supports that assertion as well.  See some of the papers in the early 2000s by JF Kalaska.  The work is done in primates, so it's difficult to gauge "perception" of the movement.  I'm sure there's been human work since then, I just haven't looked for it.

You've stumbled on an old and unanswered question that is still debated--- bordering on the issue of Free Will. The reason it is still in the realm of philosophy is because current experiments don't allow direct testing of which neurons give rise to specific thoughts. This area of consciousness is fraught with difficulties and we just can't get at an answer.
Now for a more philosophical answer.
All consciousness is generated by the brain so every thought must come from neuronal firing necessarily. The difficulty lies in the fact that thoughts themselves cause neurons to fire and one is never thoughtless so we are reduced to the chicken and the egg problem if we continue down this path. However, assuming we come from a thought free state- for example deep coma-- the first thoughts we have are indeed generated by neuronal firing so your assertion is correct.

Original thought is not perception. Perception is response to the afferent, reacting to something. Original thought is efferent not reactionary but inventive. This is the conundrum, chicken or the egg. Dennett would support that the egg creates the chicken in order to create another egg.  The egg that creates a rooster is well on the way to independent inventive thought (free will).

Your answer could be improved with additional supporting information. Please [edit] to add further details, such as citations or documentation, so that others can confirm that your answer is correct. You can find more information on how to write good answers in the help center.


text:
Can carnivores survive on a (processed) vegetarian diet? Why or why not?
There are many differences in for example the digestive system between carnivores, herbivores and omnivores.
It seems that in certain kinds of species adaptability with respect to diet is possible. What I have heard is that it is impossible for carnivores to survive on a non-meat diet.
Therefore I wanted to ask: Is it really impossible for a carnivore to survive on a vegetarian diet, even when the fruits/vegetables/plants are processed? I could see how their digestive tract would not allow for them to survive on grass, but what about certain kinds of nuts, mushrooms, or even processed plant based foods?
If it is impossible to survive on these diets, why?(With respect to either causes in their digestive system or substantial differences between meats and any type of vegetarian food.

I think this is too broad - "carnivores" is a large and loose group of species that range from obligate to facultative carnivores, and the answer to your question is likely to depend on exactly what species your are talking about.

Thank you very much for this specification. I am talking about species which are categorized under obligate carnivores.

This would be a great question here: http://area51.stackexchange.com/proposals/94068/veganism-vegetarianism

With arbitrarily broad meaning of "processed", yes. If absolutely nothing else, elemental purification and inorganic synthesis of something chemically resembling meat in nutrition is possible. Prohibitively expensive and stupid, yes, but possible. So then the question becomes exactly how much processing you need to do. Without clear bounds on that question and inadequate research on the metabolism of obligate carnivores, nothing closer than a broad stab at an answer makes sense. That said, here's a broad stab.
For instance, you'd probably need to synthesize vitamin D3, carnosine, DHA, and a handful of other things from plant extract, which is possible but difficult. Carnivores often have carnosine synthases, for instance. Cats have two distinct carnosine synthases. In terms of dietary sufficiency, that may or may not be enough. To be sure, you'd have to break it down to amino acids and build it back up again, essentially. Obligate carnivores are likely to have a number of other metabolic needs that aren't met with, for instance, pulverized soybeans. You're going to need at least one vat for fermenting raw amino acids into carnosine, and probably another for vitamin D3. Seawater microalgae contain lots of DHA, so that is probably something to look into. You could oversupplement alpha-linolenic acid instead of supplementing DHA, which might or might not work. There's not a lot of study into carnivore metabolism, so prepare to make some discoveries the hard way. Genetic studies can only take you so far, so don't try this on your favorite pet first.
In short: yes, you can raise carnivores on a diet made from plants and plant material. Rhetorical you, as in it is possible. It's probably not something you can do at home, even if you're wealthy.
(I'm assuming "feeding the vegetable matter to chickens" falls outside the domain of "processed" but it would be much easier than large-scale amino acid purification and fermentation.)

I would rephrase this to be "No, not without synthesizing certain essential nutrients not found in plants".  Otherwise you might as well say that you could also feed carnivores on a diet of "processed" air, water, and dirt.

Thank you very much for your answer. As I understood it is normal that carnosine is synthesized within animals by a natural process involving beta-alanine and histidine. (In humans the enzymes, which carnivores may lack, will decompose the carnosine into beta-alanine and histidine when taken into the mouth in that form).

Vitamin D3, in humans is not taken in as such. It is mostly vitamin D activated by the kidney and the liver. Where hydroxyl groups are added to activate it. One of the groups is the carbon 25 through the liver and the other  carbon 1. This leads to the most active form of vitamin D= 1 25-dihydroxyvitamin d3. Is it for carnivores, like humans, the case that this vitamin must be processed in their own bodies to be useful? If so, would they need meat, unlike humans, to get enough of this vitamin?
(It seems that mushrooms that have been exposed to ultraviolet b light contain high lvls vitamine d.

Calvo MS, Garthoff LH, Feeney MJ, et al. "Light exposed mushrooms: From development to market of naturally enhanced plant sources of vitamin D." Proceedings of the 5th International Congress on Vegetarian Nutrition. Loma Linda, CA; March, 2008.

As for DHA (And EPA) That seems like a workable idea! (That is if their digestive system would allow to process it) (Which I would not know why it wouldn't)

To supplement vitamin D you might not need to mess around with mushrooms. Carnivores do still have vitamin D synthesis machinery(at least dogs do) but they're too hairy to get all their vitamin D that way. Just shave your dog every so often? That might work.

Of course it is possible for a carnivore to live with a vegetarian diet. Technically you could come up with a complete meal out of vegetables and make a carnivore pup live with it. Dogs and cats are good example of it. They can learn to eat vegi-processed food and as far the nutrients needed are present they will grow and live well. To make them eat raw vegetables is more difficult.
As correctly asked by the commenters, here some links where you can find some info about:
Vitamin D3 in plants (many thinks that only meat/fish contains it)
Carnosine also can be synthesise by the body, here the main references
DHA that is contained in several veg food
Vitamin B12 from cyanobacteria

I agree with you, but you should back up your answer with sources

I'm not sure this answer is factually accurate. For example: dogs and cats differ in their ability to synthesize taurine, an otherwise essential amino acid. Synthetic taurine is cheap, but it's not possible to feed a cat "a complete meal out of vegetables" without adding certain nutrients.

Nope, the answer is wrong when it stays this general. We cannot synthesize certain important vitamins (B12 for example) and there is not plant source for it.

Ok, as soon I have time I will add some references. All the essential stuff can be found in some plant even if it could be hart to found them in the supermarket. Vit B12  for example can be synthesized very easily an thus supplemented. I am quite sure that it exists some plant, mushroom or bacteria rich in B12. Again, tomorrow I will post the sources.

Thank you very much for your answer Alec. Dogs are considered omnivorous, while cats are considered strict carnivores. Does your answer mean that cats could survive without meat? Once again thank you for your answer.

@Chris, vitamin B12 is present in lots of vegetables, here a small list of them http://www.healthaliciousness.com/articles/foods-high-in-riboflavin-vitamin-B2.php

@St.Clair Bij I think that cat can live without meat, yes. I don't think they can survive just eating salad, but I am sure that a vegetarian only meal can be prepared to support all the nutrition needs of a cat. Algae, plants, veg, beans, mushrooms, fruits (milk and egg - that should be considered vegetarian as well) the sources of nutrients on this planet are countless.

@Resonating: taurine is not an amino acid. It does not even have a carboxylate group. It is an amino alkyl sulphonic acid

@alec_djinn I am talking about B12, not B2, as you linked. If you look on the relevant list, you will see that all the B12 there is derived from animals (meat, milk, eggs...).

To conclude, here an overview of vitamin D3 in plants (many thinks that only meat/fish contains it) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651966/   Carnosine also can be synthesise by the body, here the main references http://www.genome.jp/dbget-bin/www_bget?enzyme+6.3.2.11  Finally DHA is contained in several veg food http://www.livestrong.com/article/291208-vegetarian-sources-of-dha-epa/     With this I hope to have answered all the doubts about my post. If not please let's continue the discussion...

@Chris.. sorry for the confusion.. here the right link. http://www.ncbi.nlm.nih.gov/pubmed/20108213

Beautiful Alec, I appreciate the research and the answer!

@Chris Vitamin B12 is not synthesized by animals at all. It is synthesized by bacteria in the guts of herbivores. Vitamin B12 supplements you find on the market are also synthesized by bacteria. http://en.wikipedia.org/wiki/Vitamin_B12#Sources

@CactusWoman I know. Still, there is source for us from plants.

@WYSIWYG Wow. You're right. I don't know why I thought that. I'll leave my comment as a warning to others.


text:
Consequence of Plants as Incomplete Protein Source
Some years ago, in a 1000~ level biology course we learned that the DNA essentially encodes formulas for creating proteins from amino acids. While the human body can synthesize many many amino acids, some we are unable to synthesize and we dub these as essential amino acids because we must obtain them from our diet. However, surely something must be capable of synthesizing the amino acids, otherwise they would not make it up the food chain to us, which opens the door to the possibility that animals may have varying capabilities in regards to amino acid synthesis. Presumably, this is why cats have to obtain a high protein diet, as they have high need for protein but a poor ability to synthesize them?
Moreover, in doing basic research into nutrition to plan a regular workout schedule there is some need to distinguish protein sources as not all protein sources are considered to be complete proteins because they do not provide all amino acids, or otherwise do not provide them in the right balance.  Particularly, many fruits and vegetables tend to be poor sources of protein.
For plants which are incomplete protein sources, they would seem to lack the ability to synthesize some amino acids. They also would not be able to obtain these through diet, as they're plants. Consequently, does this mean that some plants may not encode for a specific amino acid throughout their entire DNA?

You seem to miss that the concept of essential amino acids is human-centric. Why should a plant encode all the amino acids needed by a human? The plant doesn't need them.

They also would not be able to obtain these through diet, as they're plants. Plant just synthesize carbohydrates by photosynthesis. Plants cannot fix nitrogen and they are dependent on bacteria for that. Though non-parasitic plants can synthesize all amino acids they need, they may not be sufficient for humans as a diet.

Apologies, as my (limited) study was focused entirely on human biology. At the time of study, I had assumed that DNA across species was encoded using the same set of amino acids, and what differentiated them was simply what proteins they made with that given set. But later I considered that this couldn't be correct as a nutritionally incomplete protein source would suggest that a specific amino acid was not being utilized. Broadly, my question was whether the set of utilized amino acids also differs between species.

With a few exceptions among some bacteria, all species on the planet make protein from the same 21 amino acids, and the relative abundances of amino acids is very similar in proteins from plants, animals, fungi and even prokaryotes. See for example this article (available as PDF here). So protein from pretty much any food provides the same amino acids.
The idea that plant proteins are "incomplete" and lack some amino acids seems to be a myth: see for example this correspondence in the American Heart Association's journal Circulation. Plants generally contain less protein than meats per weight, but there is nothing wrong with the protein they contain. Most people in the world obtain the majority of their protein from plants. There are probably some specific parts of some plants that are not nutritionally optimal --- if you for example lived exclusively on peanuts for a year, you might experience some problems ... But any commonsense, varied plant diet will provide all amino acids. A detailed report (and some mythbusting) is here.
Regarding essential amino acids, as mentioned in comments this is a species-specific concept. Humans and most animals can synthesize about half of the 21 amino acids, while the remaining are essential. There are some species differences --- arginine is essential for cats, for example, but not for adult humans. In contrast, plants can synthesize all amino acids. But their protein composition is similar in the end.

So would the amino acid profiles listed on this site (under the protein quality box), for instance, be mostly bunk?

Well, I don't know where that particular data comes from so I can't judge it, but there is certainly a lot of unreliable stuff on various nutrition websites. These companies often want to sell nutrition supplements and tend to have little real data to back up their claims ...  There are certainly some differences between foodstuffs, since we don't eat entire plants but only some parts (see http://ajcn.nutrition.org/content/59/5/1203S.short). But generally, if you eat a varied diet, you will obtain all amino acids you need.

@WYSIWYG Right, I guess that was not very precise. I just meant that they are primary producers (obviously). Will edit.

I changed the 20 to 21 amino acids since most species also code for selenocysteine.

@terdon, selenocysteine may not be so relevant from a nutrition viewpoint since selenoproteins are rare, and the amino acid is probably a very small fraction of total protein. But okay.

@Roland I admit I'm biased since I did my PhD on selenoproteins but it's not that rare. There are 22-25 proteins (depending on how you count them) in the human genome and some animals have many more. They are also essential, those animals that have them can't really survive without them. But yes, I know I'm being pedantic, it's just that it's my field and everyone forgets about poor Sec :)

@terdon Heh, I can sympthasize.


text:
How many generations apart can a DNA test for blood relations be valid?
Suppose an American suspects he is a descendant of George Washington and he has a strand of hair of George Washington. Can a DNA test be done to prove that he is indeed a true descendant of the great Founding Father?
How many generations apart can a DNA test for ancestry still be valid?

What research have you done to answer this (interesting) question yourself? You might be interested in the question of Thomas Jefferson's offspring.

i would like to ask: " how many generations of parents can be found from all current people's dna? if all dna of all all current people is got, how many years of past parentship relations can be found from it? " but it is too short. would you like to edit your question that way?


text:
If dolphins can see sound, can they say images?
Dolphins determine their surroundings by listening to echoes. Can they mimic those echoes and communicate it to other dolphins, transmitting an "image"? Does the same go for all echolocators?

Until a day comes when you can tell one dolphin what image to "transmit", and then ask another what image it "saw", it's pretty hard to imagine an experiment that would let you test that idea.

Humans can get some spatial information from the sounds that they hear.  Close your eyes, and listen to some good stereo mixes of music through headphones, and you will get a sense of a "space" around you with different instruments at different locations within that space.  Now try listening to the same mix in mono (or, with just one ear bud in place.)  All the spatial information is gone!  Whatever sounds one dolphin is able to make, it's still just one dolphin---just like one earbud...

Cheers, that makes sense.

Humans and dolphins can selectively encode which elements of an image they wish to transmit using serialized code.
The transmittance of images in single bursts to multiple recipients doesn't exist except in cameras and projectors, in single beams. It's highly unlikely even that humans use any long distance echogram projection technology.
Echogram transmittance would require 2d graph imaging organs through which to redraw and send the echogram in the direction of the receiver, same as the film/pixels and lense in a projector.
Sound is a lo-fi acquisition method. So bouncing an echogram to and from a source makes it even more lo-fi.
They would have to direct the echogram to a specific respondant using a kind of rotation, and to aim it just right.
The lense that the dolphins use to focus the sound is called a melon, and it's made of wax and fat. I think it's highly unlikely that they have a kind of image grapher and lense system to speak echograms. Nice idea!

I edited the response so that it makes more sense.

I have just asked a similar question in scifi.stackexchange and the reason is, I believe your idea can be found in a book written perhaps 60 years ago. I asked who the author was and/or the name of the book.
I am pretty sure this has been substantiated by researchers -- not recalling how the experiment was set up but I think it essentially involved simulating the dolphin echolocation process and then comparing sounds the dolphin emitted when shown the object or perhaps the researchers produced the sounds for a dolphin and asked the dolphin the choose from among objects.
So while a human might draw an object to explain to another human what they wanted, etc., a dolphin could do the same thing with sound. Perhaps their nouns all resemble the signals that come back during echolocation but I would also bet they abbreviate them since their probably is a lot of excess information in the signal from an actual object.
They would have the natural idea of "instance" and "class" (I speculate). And if cetacean language does consist of abbreviated signals from objects, I do not wonder why they have such large brains.
Here is a link that seems to indicate the answer to your question is "yes":
https://www.cymascope.com/cetacean.html

Your answer is much more likely to receive a favorable response if you [edit] it to include supporting references (primary literature is best; a commercial website with no references is of no value). Without that support, your answer is indistinguishable from opinion and not appropriate as an answer on this site. ——— Please take the [tour] and then consult the [help] pages for additional advice on [Answer] effectively on this site and then edit or delete your answer accordingly. Thanks!


text:
How can I tell if a protein has been denatured?
So i recently done an experiment using egg albumin, and we had 5 test tubes. the goal was to see if they have been denatured.
1- heat
2-acid (HNO3)
3-base (NaOH)
4- Alchol (ethanol)
5- heavy metal ions (AgNO3)
So some of the test tubes became cloudy/milky and some clear. Is it the clear ones that has been denatured? I don't know how to tell.
Thanks in advance :)

What is your starting state? If it was clear before you added the factor of change and the protein was in its normal conformation, then what does that say if solution stays clear or becomes cloudy?

untreated egg albumen is, contradictory to the colloquial term 'egg white', a clear mass. That is its native state.

In my experience, when protein denatures, it typically aggregates and precipitates from solution. I would expect a denatured protein to create a cloudy solution, or actual precipitates in the form of little globs or fine wisps. A solution where protein is correctly formed and solubilized in the solution should be clear.


text:
Are inadvertent environmental catastrophes also examples of natural selection?
I just want to understand the concept of natural selection and its relation to evolution.
Evolution by natural selection occurs when we have hereditary trait(s) that causes an effect on reproduction rate of a population, either towards the positive, and thus deemed as beneficial or towards the negative and thus labeled as harmful.
Evolution by natural selection would result in keeping the beneficial trait(s), and wiping out the harmful ones.
The idea according to Darwin is that the slightest harmful effect a hereditary trait(s) would bring to a population then with time it would result in extinction of the population with that trait(s). [On the origin of Species, p.78, chapter: natural selection: "On the other hand we may feel sure that any variation in the least degree injurious would be rigidly destroyed"].
Therefore natural selection could be viewed to result ultimately in washing out of injurious traits, and only promoting beneficial traits. So natural selection can be the cause of extinction of some genotypes, and ultimately of some species.
In this sense natural selection can be considered as a creative natural tool, like a rubber wiping bad intermediate solutions, and only keeping the correct steps, thereby facilitating reaching into a solution.
Now suppose that we have a population of living subjects with varying heritable traits on an Island, and those had equal fitness over a very long period of time, so they were pretty much adaptive to their environment. Now suppose a volcano erupted or a big comet stroked that island that ended all life in it. Lets suppose that the genotypes of that population is not present outside of that Island. So these genotypes became extinct.
Here this event doesn't have the same functional genre that natural selection had, it actually didn't act in a differential manner promoting those genotypes with better fitness and wiping out those with lower fitness. No it actually was NOT fitness dependent at all, it simply squashed all life forms without regards to whatever feature was brought up by the different genotypes, all were simply extinguished.
Now can we label this event of indiscriminative extinction to be the work of natural selection also? Or we just label it as inadvertent environmental factor?
If the latter, then are those inadvertent environmental factors part of the mechanism for evolution?

Let me give another example:
The beetles stochastic example
Suppose we have a population of brown and green beetles, now suppose that we divide the place they live in into two territories A,B, now suppose that the movement of beetles across those territories is random, so at some moment of time all brown beetles happen to be in territory A, other times they have different distribution, and as said the movement pattern is totally random, i.e. there is no significant difference in the pattern of movement of both genotypes of beetles across territory A and B. Now suppose by the act of randomness a moment came where all brown beetles were located at Territory A, while some of the green beetles were in territory A and others in territory B, and suddenly came a big comet and hit territory A at that time that caused all the brown beetles to die, and also caused all green beetles on territory A also to die, but since territory B was not hit, the green beetles in B remained a life.
Now a moment of evolution did occur, since a change in the heritable characteristics of the beetle population did occur. But that change was merely accidental, there was no role attributable to fitness of the green beetles that resulted in their survival, it was a mere random event that caused all of the brown beetles to die. In some sense it's a kind of a stochastic environmental factor that caused that extinction. Fitness of the green beetles didn't have any role in that case of differential survival.
This can be called selection, it is environmental kind of selection, BUT it is NOT the outcome of differential fitness of the genotypes in that environment.
Now this moment in evolution is it described as an event of evolution by natural selection?
More broadly speaking, is it the case that any point of change in the heritable characteristics of a population (i.e. evolution) that is merely due to an environmental factor [like the above example], would qualify as a case of evolution by natural selection? or only those points where the resultant change is attributable to fitness differential that is genotype determined?

FYI, you misunderstand the quote: "On the other hand we may feel sure that any variation in the least degree injurious would be rigidly destroyed". This does not suggest that any deleterious variation would result in extinction of a species.  It's a restatement of what selection is.

if you read the whole chapter of natural selection in Darwin's book "on the origins of species" then you'ed definitely get the impression I'm speaking about. In the struggle for life, Darwin highly adheres to Malthus principle that resources are not enough that ultimately even the slightest disadvantage a heritable trait would bring with it then this would be enough [over sufficiently long period of time] to cause extinction of that trait. Any variation that causes negative shits in balance in the struggle for life, would cause extension. That's what I mean here, and what Darwin meant.

DO NOT read Darwin expecting to understand the concept of natural selection and its relation to evolution. Darwin wrote over 150 years ago, and is entirely irrelevant to modern evolutionary theory. You are not educating yourself; you are simply confusing yourself, and wasting everyone's time by expecting people to explain obsolete, irrelevant concepts as if they're currently important. Darwin was a great thinker and set some foundations for modern evolution, but he is now important only as history, not science.

You can find good courses on-line, such as the one from Yale: https://oyc.yale.edu/ecology-and-evolutionary-biology/eeb-122/lecture-3 (Look at the next lecture on drift as well)

Is a change in allele frequency resulting from a catastrophe evolution by natural selection?

The catastrophe itself is an example of a change in environment that brings with it a change in selective pressure. The events you describe (a volcano eruption, or a comet strike) would select for existing variation in the population. Heritable traits that are more common in those surviving the event would have been selected for. This represents natural selection.
Consider the description of natural selection from the UC Berkeley Understanding Evolution Course. We need the following things: variation, differential reproduction, and heredity.
Provided there were some variants that are able to survival, and their survival is the result of some heritable trait, this certainly fits the bill.
What if nothing survived?
This is highly implausible. I'm not aware of any event where this has occurred. Volcanic eruptions are colonized by microorganisms, and the K-T extinction certainly benefited us. If you are focused on, e.g., a specific population that happens to not have enough variation to survive the catastrophe, then that particular population has become extinct. This becomes more plausible the smaller and more homogeneous the population is.
To be honest, I'm not sure if complete loss of a heritable trait that made the population susceptible to the catastrophe (e.g., limited flight range in a bird population that was entirely unable to escape an eruption) would be considered natural selection in the event that the entire population was lost. From a framework of a larger population of birds that included that trait in some birds not on the island in question, I suspect it would, despite the fact that the birds without the trait may not have been exposed to the selective pressure. I would argue that, because there is a decrease in the frequency of a trait in the population due to selection against that trait. Perhaps I should ask a question about it. I welcome any comments or edit suggestions on this point.
Changes that are not due to natural selection
As discussed in a chat with @BryanKruase, changes in allele frequencies that are associated with, but not on the causal pathway to failure to reproduce, would not be considered natural selection. So, selection of birds with a longer flight range, provided that flight range is heritable, would be considered natural selection. If those birds also happened to have more green feathers, an increase in the frequency of that trait would not be due to natural selection. One need not invoke a rapid change in environment (seen from one perspective as a catastrophe) in order to see both types of changes (the trait under selection as well as those associated with that trait). From my perspective, that may have obscured the question. As Bryan pointed out, one should be careful not to overestimate natural selection as the principal cause of evolution.
Your green/brown beetle example would be an example of a change in a heritable trait that is not evolution due to natural selection. Here a random event led to all the brown beetles failing to reproduce, but the brown trait itself was not selected for or against. Speaking of the trait, then, and accepting your hypothetical, we can say that the change in this trait was not due to natural selection.
A few additional comments on your question:
On reading Darwin: I'm glad you're carefully reading Darwin. It's been a while since I've done that. I would recommend you not get too caught up in whether something fits with his description. That was the state of things 160 years ago.
On an "inadvertent catastrophe": this phrase is a little confusing. Your examples are natural phenomena. I'm not sure you mean to distinguish your examples from purposeful changes, e.g., for an experiment.
On changes "merely due to an environmental factor": selective pressures in natural selection are always due to an environmental factor of some sort or another.

The event killed ALL the living population in the island, where is the selection?

@ZuhairAl-Johar if that happened, that's the selection. I'm not sure what is unclear there? No traits allowed for survival under that selective pressure.

evolution by natural selection occurs when we have variation in heritable traits that cause differential fitness that would result in extinction of the less fit genotype. In other words "natural selection" is a function of differential fitness. But here the catastrophe caused extinction was not a result of variation in heritable traits, definitely this point in evolutionary history (i.e. the catastrophe causing this massive indiscriminate extinction) is not the result of what Darwin was speaking about in his chapter "natural selection".

Its true that the catastrophe had resulted in a change in the heritable characteristic of the total living population on earth, since that would lack the ones that became extinct, and a moment of evolution had occurred yes, but that was not due to evolution by natural selection, i.e. that change in hereditary characteristics didn't result from a change in fitness of completing genotypes. It was a blind force having no direction at all. The natural disaster didn't select for anything that it acted upon, it destroyed them all.

@ZuhairAl-Johar the catastrophe is the environment, not the selection. In a hypothetical and extremely implausible case that has never occurred (100% of life everywhere is abolished), absolutely everything was selected against because there wasn't a variant that allowed survival in that environment. In any other case, something is selected for.

I think there is a problem in terminology here about "selection" itself, to me selection cannot be "totally selected for" and cannot be "totally selected against", to me those are example of NO selection, because there is no differential effect of that environmental factor on genotypes. If you look at Darwin he explicitly says that no selection occurs if the there is no extinction of one of the genotypes, similarily to me if it results in extinction of all the genotypes under its effect, then no selection had occurred under effect of that factor.

@ZuhairAl-Johar consider that your hypothetical (all life is abolished) never happens and you will see that selection does occur. There are organisms that survive the catastrophe. If they have heritable traits that allowed them to do so (mobility and ability to predict or detect the event, so they were out of the primary blast area, heat tolerance, tolerance reduced light after the fact), then those traits were selected for. Those organisms without those traits were selected against.

Yes of course, under this scenario there is indeed an example of selection that occurred due to the heritable characteristics of some genotypes, that enabled them to evade the catastrophe, definitely this would qualify as an example of natural selection. But that's not the question of mine really, its another scenario. In my scenario there was no differential output, truly there is some life remained outside the Island, but this is not due to the beneficial traits of those genotypes, it was merely due to the comet not striking them, so their survival is not attributable to their fitness.

what I'm trying to say here, is that I think [I might be quite wrong of course] that it would be more plausible if we restrict "natural selection" to situations where "differential survival" [remaining in existence] resulted from "differential fitness", and preferably under a predictable setting! If some genotype survived some environmental impact not because of its own characteristics, but just because of mere chance that this environmental impact was directed away from it, then this better not be regarded as an example of natural selection, call it inadvertent environmental selection.

@DeNovo In my view, which I would accept a challenge to, the key for natural selection is that there is differential survival because of a heritable phenotype. Living on a particular island is not a heritable phenotype by itself, and an event that kills every organism is not natural selection. I might be wrong to lump it in with genetic drift, but I contend it would be more similar to drift than selection, there's basically just been a bottleneck if some subgroup is wiped out.

@bryankrause I should edit to clarify. I don't believe there has ever been a case where survival or failure to survive a catastrophic event would not depend on at least some trait with some heritability (other than in the marvel comic universe)

@thanks for this informative answer, but can you please answer the beetles example question, this is a later edit to my question, in that particular example, it appears that natural selection is not playing any rule, since the survival of the green beetles is not attributable to their fitness at all.

@ZuhairAl-Johar your welcome. I've addressed the beetles question.

thanks for your very informative answer, I now know matters better. But I just want to make sure of one point as regards my beetles example, you said it is an example of change in heritable traits of a population that is not due to EVOLUTION. I thought that a moment of evolution is a moment where a change in the heritable characteristics of a population occurs, so my example defines a moment of evolution, but that moment is not caused by natural selection. I mean that's my understanding of the matter. But when I saw you saying that it is not due to evolution, I need to fathom this.

@ZuhairAl-Johar that was a word finding problem/brain fart. In a bit I will edit to fix.

The idea according to Darwin is that the slightest harmful effect a
  hereditary trait(s) would bring to a population then with time it
  would result in extinction of the population with that trait(s).

Citation?  I certainly don't think any modern biologist would claim that a single deleterious allele will doom a population.

Therefore natural selection could be viewed to result ultimately in
  washing out of injurious traits,

In real life, there is no infinity far away "ultimate" point to be reached.  What's deleterious today might be beneficial if the environment changes.  And the environment is always changing.

Now can we label this event of indiscriminative extinction to be the
  work of natural selection also?

I don't see why you would, since survival was not influenced by genetics.

If the latter, then are those inadvertent environmental factors part
  of the mechanism for evolution?

Well, if it kills every single organism, I don't think we can say that population is evolving any more.  But bottlenecks randomly and radically changing allele frequencies are hardly an unknown mechanism for evolution.

I've given the citation, according to Darwin, he believed in Malthus rule about geometric growth of populations with arithmetical growth in supply of food that eliminating that abundance. So over time any slight injurious trait would result in extinction of that genotype, due to that struggle for life, since by Malthus law its impossible for all of them to remain extant.

+1, I think a key issue here, which you point out, is that there is no inherently "good" or "positive" trait, the value of the trait depends on the environment, which is changing.

Simply citing Maltheus does not mean that Darwin really believed that a single deleterious variation would destroy a species.  The strength of Origin of Species was all the work Darwin had put into observing variety across a number of different organisms.  I don't think he ever said "Well, these barnacles are going to be extinct soon, because I observed this undesirable trait in one of them"

@swbarnes2, I've given a clear reference to Darwin, and the tone of his speech clearly imparts what I've said here, "the least injurious"a trait would be then this would cause extinction, but I did NOT say "soon". I didn't cite Malthus, I've cited Darwin account and Darwin's own claims about malthus principle in relation to the struggle for life, that's not my citation, that Darwin's citation himself, read his chapter on natural selection very carefully. –

You are missing many points. Darwin is almost entirely irrelevant to modern evolutionary theory and has been since the modern evolutionary synthesis in the 1940s (and even more so since Kimura and other modes of evolution), so arguing about what Darwin said is a waste of time. It's like claiming Egyptian hieroglyphs disprove internal combustion. Further, trying to map Darwin's arguments onto modern genetics is silly; Darwin had no clue about genetics, and entirely misunderstood heredity. Your reading of Darwin is wrong, too, but I won't bother explaining why since it's so irrelevant.

Natural selection is an important part of evolution, but not the only part
Evolution is described as changes in heritable characteristics over time: you can look at changes in allele frequencies and call that evolution.
Genetic drift, for example, describes genetic changes that are caused by random sampling rather than selection. A natural disaster (if we assume it acts only to kill off some individuals, rather than changing the environment), could hypothetically contribute to genetic drift.
Consider some population of a species of birds on a group of islands. The birds can fly between islands, so they interbreed but not at the same rate (i.e., they are more likely to breed within their island than between islands). Therefore, if we look at allele frequencies, they are not identical. They will be especially likely to drift apart if they aren't especially important to survival (an example in humans could be something like eye color).
One day, all the birds on one of the islands die by some disaster. If we look at allele frequencies across the whole population across all the islands, those frequencies just suddenly changed: any alleles that were more common in the doomed island were just reduced. Evolution just happened (heritable characteristics just changed), with no selection.
These effectively random changes can be quite important evolutionary forces over the long run, especially when population bottlenecks occur, in which case a small population survives rather than is wiped out.

I'll concentrate on your sentence .., with NO selection.  So the above is not an example of natural selection. Is that correct?

@BryanKrause on closer reading, I disagree. If the birds suddenly died due to stochastic effects, this is not natural selection. If the birds on one island suddenly died because of a natural event, this is natural selection. The fact that the event is a catastrophe or sudden does not make it any different from the rare visit of a particular predator, a change in tide patterns, extinction of some food resource, or the sudden presence of antibiotics, complement, or antibodies.

@DeNovo It's only natural selection if a heritable phenotype is involved in the process, by my view. An island that is randomly destroyed by disaster is in fact stochastic. If some survivers remained because of protective heritable phenotypes then that would be natural selection. I'm curious how RemiB would weigh in.

@BryanKrause I would agree that if the phenotype wasn't involved in the selection process it wouldn't be natural selection, but I can't imagine a case where that would be true

@DeNovo I agree it's a bit of an artificial scenario, but read the OP's scenario: by random chance, individuals of different phenotypes are in two regions. One region is destroyed at random by a natural disaster. Maybe a hurricane floods an island and kills every member of a species on that island but not other islands. Allele frequencies are changed subsequently by this random event, which did not target one region or the other based on anything related to the heritable phenotypes of the individuals affected.

@BryanKrause neither of those events are random, though. I think the tendency to see the effect of rare events as something other than natural selection has to do with the simplification when evolution by natural selection is taught, that an environment is constant over many generations. Some regions are susceptible to hurricanes. Some aren't. Arriving and staying in that area is going to be associated with some heritable trait. Not being able to detect and leave or find shelter is also going to be associated with some heritable trait.

@BryanKrause the fact that the hurricane is rare, or causes a sudden change, doesn't prevent it from exerting selective pressure when it occurs.

@DeNovo " Arriving and staying in that area is going to be associated with some heritable trait" - not necessarily. Europeans are more likely to have blue eyes than people elsewhere. Nothing about blue eyed people made them up and migrate to Europe. If Europe got hit by a meteor and the fraction of blue eyed folks in the population was therefore reduced, I don't find it appropriate to call that "selection." That isn't to say that such an event couldn't also involve selection, but the trait I described does not provide fitness against meteor strikes.

Let us continue this discussion in chat.


text:
If bacterial resistance randomly occur, then why limit broad-spectrum antibiotic use?
If there is importance to study some discipline, then one of the main matters is its applications, so besides the primary goal of knowing the truth of the matter regarding what that discipline is investigating, applicability or usefulness of that study in other fields or in the field itself is a very important matter. I'll direct my attention here to Evolution, and its mechanisms. So accordingly if something that I personally want to come up with is application of that knowledge to the field of my work.
In reality we don't study evolution extensively at college level in medicine, since it doesn't have a direct clinical impact on the diagnosis and treatment of patients in most of the cases. However, one possible area of interaction is "bacterial resistance to antibiotics", since this is related to "mutations", and generally viewed as a mechanism whereby the bacterium adapts to its environment.
Now all of my life in medicine from college through specialty and academic teaching, we've never ceased being reminded about not dispensing antibiotics liberally, and the main concern outlined is "emergence of resistant strains of bacteria" due to this liberal use of antibiotics itself. There are other reasons of course, like side effects and cost, but they are not the main concern most of the times.
During my recent review of Evolution, looking at the introductory courses that were cited to me by many participants here, in particular this page of Evo101 titled "Mutations are Random" I was really shocked to know that even the mutations that resulted in bacterial resistance were not "directed mutations", i.e. it is not the case that the exposure to the antibiotic caused the bacteria to have that mutation in the first place, actually the page mentions Esther and Joshua Lederberg experiments showing that those resistant bacteria were already there before the population was exposed to the antibiotics?
So why have we been always reminded by bacteriologists of limiting our antibiotic usage if emergence of drug resistance is not due to exposure to it?
Actually, its not only that, many lectures we attend, which are pretty much delivered by official bodies, does mention of emergence of antibiotic resistance as a DIRECTED mutation response to exposure to the particular antibiotic, that almost most of us we clinicians became to think that this is a fact. For example hospital bacteria are of the most resistant ones, especially those in intensive care facilities. The association between exposure to antibiotics and emergence of drug resistant bacteria to them is almost hammered in our brains, that to discover that the mutation was already there before exposure to the antibiotic seems quite shocking, at least to me in person.
My question here is the following:

Is it a scientific fact that emergence of bacterial resistance through mutations is always random, i.e. in the sense that it is not a directed response to exposure of the population to that antibiotic?

For instance this seems to be a counter-example.
If that is the case then why bother about liberal use of broad-spectrum antibiotics? I mean as far as emergence of bacterial resistance is concerned!
I mean its not the case that I'm going to eradicate the "useful bacterial" that could rival the pathogenic resistant bacteria, by that liberal use of broad-spectrum antibiotics. If that happens temporarily we can in principle replace them back, like with the use of probiotics.
During my surfing of the web I found that page addressing the same point, but the responses are not that explicit, and far from being convincing?

See related questions https://biology.stackexchange.com/questions/55372/have-bacteria-evolved-antibiotic-resistance-in-a-laboratory-setting https://biology.stackexchange.com/questions/28379/does-long-term-use-of-antibiotics-in-humans-actually-lead-to-a-greater-risk-of-i https://biology.stackexchange.com/questions/14350/can-antibiotic-resistant-bacteria-compete-with-normal-one-in-an-antibiotic-free

Also see https://biology.stackexchange.com/q/48724/3340

You're correct, this is extremely relevant, and it's unfortunate that your medical education didn't include good instruction about evolution.
You point to some very useful and interesting studies. I'm particularly fond of the studies that demonstrate the early existence of antibacterial resistance genes, e.g., in ancient permafrost.
Now to your question

Is it a scientific fact that emergence of bacterial resistance through mutations is always random, i.e. in the sense that it is not a directed response to exposure of the population to that antibiotic?

I think the issue here is a conflation of two separate concepts. Mutation is one mechanism for producing variation. Mutation can be understood as a stochastic process, causing changes in the genome of an individual by chance.
Evolution occurs because of existing variation. Evolution is not a stochastic process. It is a biased process, a change in the distribution of existing variation.
The emergence of antibacterial resistance is evolution that results from selection acting on existing variation. Emergence here refers to emergence of a resistant variant within a population. Selective pressure (application of antibiotics) causes a predictable change in the frequency of genes that would allow reproduction in that environment, the frequency of existing resistance genes increases in the bacterial population.
Though there is evidence for important antibacterial resistance mutations pre-dating the use of antibiotics, this does not rule out the occurrence of spontaneous mutations, as demonstrated in the article you linked. The production of genetic variation by random mutation can be followed by a rapid increase in the frequency of a new genetic variation that is selected for in a given environment. This can be particularly likely in organisms with high error rates, short generation times, and large numbers of individuals. The spontaneous mutation isn't directed, as you say. It is random. The selection of that particular random mutation is directed, though.  Once the random mutation occured, then we can say the variation exists. Then selective pressure acts on existing variation, allowing evolution, a change in the frequency of the, in this case, gene for resistance.
Goodman & Gilman, one of my go to pharmacology references, actually has an excellent discussion of these concepts as they relate to antibacterial resistance, in Ch. 48, under the subsection EMERGENCE. There is a good discussion of the various mechanisms of emergence, but this general statement is helpful:

Mutations are not caused by drug exposure per se. They are random events that confer a survival advantage when drug is present. Any large population of drug susceptible bacteria is likely to contain rare mutants that are only slightly less susceptible than the parent. However, suboptimal dosing strategies lead to selective kill of the more susceptible population, which leaves the resistant isolates to flourish.

I think most medical schools around the world don't have a meticulous course on evolutionary biology. Actually the trend is going more and more towards clinical based teaching with reduction of most of what is used to be taught in basic sciences in colleges before, only those parts relevant to clinical practice are highlighted nowadays, the others are actually selected against and they are vanishing with time. I don't know why evolution was already minimal, and even in the future it would most be mentioned  in relation to possible applications only.

@ZuhairAl-Johar there is a lot to teach in medical school. In the US, it's in the prerequisites for admission, and taught in this context in microbiology and infectious disease.

Yes in where I live its also taught in secondary schools but not that deep anyway. I'm speaking about matters related more specifically to medicine. I see that Remi.b had pointed to evolutionary medicine. which unfortunately never been even heard of in most medical schools

The mutations are random, the survival and spread of bacteria with said mutations is NOT random.
Evolution and selection are situational.
The careless use of antibiotics causes those mutations and bacteria to spread because they out compete others without resistance. However, often these will not outcompete without antibiotics being present. Often mutations that produce resistance are detrimental when antibiotics are not present, or more precisely the downsides of the mutation are more than offset by the benefits of resistance when antibiotics are present.  Meaning even when they occur mutations the produce resistance die out quickly without antibiotics.
Even when they offer no advantage of disadvantage without the presence of antibiotics normal genetic drift can eliminate them, but when antibiotics are present and a mutation occurs the mutation then offers an advantage and spreads. That means a person is more likely to catch a strain that is resistant than if their was no antibiotics present in the bacteria's environment.
Note the "environment" can be anything from the greater ecosphere down to an individual patient. and population can be the population inside an individual or the population of bacteria across the globe.
lets try a pair of scenarios
In each the mutation for resistance occured in 1% of the population of bacteria.
Scenario 1  no antibiotics. You have a 1% chance of catching a resistant strain.
Scenario 2 Antibiotics present. Now selective pressures quickly change the population so that resistant strains now make up the majority (we'll say 75%). Now you have a 75% chance of catching a resistant strain, and worse those resistant strains now have a high chance of meeting other strains with other resistances or of having another resistant mutation occur (now 1% of 75% instead of 1% of 1%) this means the population becomes even more resistant and it does so rather quickly until no antibiotics work.
So emergence, AKA exposure of humans to resistant strains, IS due to use of antibiotics.
Careless use of antibiotics include.

Use of antibiotics on people/animals/things who do not need it.
Disposal of antibiotics in the environment.
Incomplete courses of antibiotics.

But there is a hidden forth and fifth concern, that is the one your paper is concerned with. Patients and doctors are humans and each of these things will inevitably happen, patients fail to take drugs, or impure drugs are improperly disposed of or a hundred other errors expose bacteria population to antibiotics. So a further concern about having useful antibiotics, by limiting which antibiotics we use, that is by only using common ones unless absolutely necessary, we are minimizing the chances of resistance to those less used antibiotics so we have something that works when we run across a resistant strain.
Lastly people already have bacteria present in their system so these microbes can be exposed to antibiotics targeted at other unrelated infections, thus encouraging resistance. Some are even protected by natural barriers that reduce exposure to antibiotics used to treat other things, like bacteria on the outside of the skin for internal antibiotics. Worse, bacteria can transfer resistance horizontally so these microbes can then share resistance with later infections. So even using  antibiotic A correctly on a patient to kill microbe X can lead to microbe Z developing resistance just because the treatment for X is not enough to kill all Z. Staph is particularly prone to this since it is everywhere. So even if you use antibiotics correctly you can still produce resistant strains of other bacteria.
As a side note some confusion is caused by is a quirk of language and terminology in the study of evolution. If X produces an environment in which a mutation that produces trait Z is favored causing that mutation and thus Z to spread in a population often scientists will just say X caused Z, just to save time. humans are lazy and typing out "X produces an environment in which a mutation that produces trait Z is favored causing said mutation to spread in the population and thus Z to spread in a population." takes much longer and uses more space than "X causes Z to spread" or just X causes Z. Other evolutionary scientists know what they mean but it can be confusing for everyone else. It is not a great practice but jargon creeps into all science.
As a personal note it has always been a concern for me that medical schools don't require an understanding of evolution at least for research fields; infection, cancer, and a million other weird quirks of anatomy and physiology are caused by evolution or evolutionary baggage. Heck infection and cancer ARE evolutionary competitions, and some of the most predictable ones.

I see what you mean. But still there is some difference! The argument is: if the use of a particular antibiotic itself is not the direct cause of a mutation causing resistance to it. Then we shouldn't be afraid form using it for that concern, because simply its not there! As for the argument you've presented what we can do is to simply use broad spectrum antibiotics but with subsequent replacement of the NON-Pathogenic bacteria that are sensitive to that antibiotic. This way we'd change the bacterial environment towards the non-pathogenic bacteria, and try eliminate the pathogenic ones.

Let me specifically present my argument further so that you get the exact context of what's going on in medicine. A clear example is staphylococcal aureus resistance. You hear a lot of call's from bacteriologists not to use the strongest guns against them, the idea is because resistance to even those powerful guns would rise, and this would render us defenseless.  Clearly this is not due to the situation you described, since it would be applicable to lower guns as well. What we often hear is that exposure to this strongest antibiotics itself will cause a mutation causing resistance to them!

for example see this link https://www.ncbi.nlm.nih.gov/pubmed/16271060

@ZuhairAl-Johar Are you saying that's simpler to constantly replace the environmental microbiome than judicious use of antibiotics? What?

@Cell, of course not. I'm saying that we can do that sometimes if we are pushed to. Of course judicious use of antibiotics is already needed for many reasons, not just the emergence of resistant strains.

Let us continue this discussion in chat.


text:
Directed evolution: Point mutation vs Insertion-Deletion vs Shuffling
When attempting enzyme function improvement via Directed Evolution I can see three different strategies to generating variation for the gene sequence:

Point mutations
Insertion / Deletions
Shuffling

Is there a systematic difference between how successful each of these approaches are likely to be for a particular gene or in general? Does one choose one over the other approaches in any specific project based on any characteristics / goal differences?
A related question: On a methodological front, I know one can use error prone PCR to get #1 i.e. point mutations.
What are similar techniques for #2 & #3? i.e. How does one execute gene shuffling or Insertion / Deletions in practice?

In general, point mutations are introduced in the proteins of interest during directed evolution. These can be specific mutations in the active site of an enzyme if you would like to change its specificity towards a new substrate, for example. The point mutations can be introduced with primers when you amplify your gene of interest. However, if you don't know specifically what changes to make, then yes, a way to generate mutations is by error prone PCR or by Quick change PCR. If you'd like to see if a certain amino acid change abolishes activity/stability/etc, you would do Alanine scanning (https://en.wikipedia.org/wiki/Alanine_scanning).
I haven't heard much about introducing deletions or insertions for directed evolution. First of all, they have to be in-frame, so that the overall coding sequence does not change. People are usually introducing epitope tags on the N- or C-terminus for two reasons: 1) to purify the proteins; 2) to increase its solubility. But in general, the introduction of deletion will lead to unpredictable changes to the 3D structure of the protein of interest.
The DNA shuffling is very often used for directed evolution. Here is a figure from a Nature paper [1] describing DNA shuffling. The way it is usually performed is by using sequence homologs of the protein of interest. The different fragments can be obtained by PCR-amplification and introducing short overlaps with the neighboring fragments. The fragments can be then assembled by various methods, including Gibson assembly and homologous yeast recombination.  The advantage of DNA shuffling over introducing single mutations is that you have to screen fewer mutants and the activity/stability of the protein could be improved several hundred fold more.

DNA shuffling figure from [1]
Interestingly, a DNA shuffling using a method called SCHEMA [2] was developed in Chris Voigt lab. Shortly, SHEMA is a computational algorithm used to identify the fragments of proteins, or schemas, that can be recombined without disturbing the integrity of the three dimensional structure. It is based on the 3D structure (of one of the parents) and an alignment of the parental sequences. It calculates the interactions between residues and determines the number of interactions that are disrupted in the creation of a hybrid protein. A window of residues w is defined and the number of internal interactions within this window is counted. The window is slid and the schema profile is created. For example. in the figure below, the number of interactions that are broken in the possible chimeras are 0 on the right chimera and 3 on the left chimera. The right chimera will be used in the screening.

SHEMA method from [2]

Thanks @Gergana. I have posted a follow up question. Would love your comments if you can! http://biology.stackexchange.com/questions/45572/why-is-dna-shuffling-more-efficient-than-point-mutation


text:
Can threat to survival increase mutation rates in germline cells?
Can stress that is related to a threat of survival of a population of animals or plants in some environment, like due to hunger, thirst, fear from predators, etc..; results in an increase in average mutation rate in germline cells of individuals of that population, thereby increasing the likelihood of producing heritable trait(s) that might be beneficial to that population in combating those adverse survival conditions in that environment?
In bacteria this is known as "Stress Induced Mutagensis"
Is there something comparable to that in animals and plants?

Well... since I can't delete this accepted answer... it's going to be a reverse ferret, to some extent. One 2014 review by Ram and Hadany lists a fair number of SIM occurrences outside of bacteria:

Stress-induced mutagenesis (SIM)—the increase of mutation rates in stressed or maladapted individuals—has been demonstrated in several species, including both prokaryotes and eukaryotes. [...] SIM has also been observed in yeast, algae, nematodes, flies and human cancer cells.

The one for algae (Goho and Bell, 2000) appears/claims to have been the fist:

Cultures of Chlamydomonas were exposed to a range of relatively mild stresses for a period of 24 h. These stresses comprised high and low temperatures, osmotic stress, low pH, starvation and toxic stress. Fitness was then assayed as the rate of division of isolated cells on agar. We found that there was a strong tendency for stressed cultures to have lower mean fitness and greater standardized variance in fitness than the negative controls which had been cultured throughout in unmodified minimal medium. The same tendency was shown, as expected, by positive controls which received mutagenic doses of ultraviolet irradiation. We concluded that the most reasonable interpretation of these observations is that mild stress increases the genomic rate of mutation.  This appears to be the first time that this phenomenon has been noticed in eukaryotes.

The paper cited for Drosophila, Sharp and Agrawal (2012)

Our results show that mutation rates are sensitive to genetic stress, such that individuals with low-quality genotypes will produce offspring of even lower genetic quality, in a mutational positive feedback loop. This type of variation in mutation rate is expected to alter a variety of predictions based on mutation load theory and accelerate adaptation to new environments. Positive mutational feedback could affect human health by increasing the rate of germline mutation, and possibly somatic mutation, in individuals of poor health because of genetic or environmental stress.

Clearly this one is quite bold in extrapolating its findings.
And long story short, the paper on nematodes (Matsuba et al., 2012) finds a temperature dependant mutation rate.
What seems to be the weak point in these paper, and perhaps why a more critical review of Lynch et al., 2016 of SIM doesn't mention them, is that no explicit mediating mechanism appear to have been identified in these studies on eukaryotes. In bacteria (e.g. the paper linked by the OP) how SIM works inside the cell is pretty well understood, there are in fact several mechanisms that all respond (convergently) to various forms of stress.
There's an acknowledgement (in the Drosophila) paper, that such mechanisms in eukaryotes might differ from bacteria

The sources and mechanisms underlying this variation have been best studied in microbes, but the sources of variation in microbes may differ from those in multicellular eukaryotes for several reasons. [...]
In animals, mutation rate varies among genotypes, although the functional sources of this variation are unknown. [...]

It does go on into some theories how it might work.
As for yeast, Rodriguez et al. (2012)

Mismatch repair (MMR) is a major DNA repair pathway in cells from all branches of life that removes replication errors in a strand-specific manner, such that mismatched nucleotides are preferentially removed from the newly replicated strand of DNA. Here we demonstrate a role for MMR in helping create new phenotypes in nondividing cells. We show that mispairs in yeast that escape MMR during replication can later be subject to MMR activity in a replication strand-independent manner in nondividing cells, resulting in either fully wild-type or mutant DNA sequence. In one case, this activity is responsible for what appears to be adaptive mutation. This replication strand-independent MMR activity could contribute to the formation of tumors arising in nondividing cells and could also contribute to mutagenesis observed during somatic hypermutation of Ig genes.

I guess a weak point of this paper vis-a-vis of SIM (which they only mention in passing) is that it's not obvious in their setup what the stress was. Basically they saw (adaptive) mutation-rate change (in response to the environment), but they don't pinpoint what exactly they think the stressor was. So this paper is a way the reverse of the other three I, i.e. the mechanism is clear, but stress is not.

but in humans stress has been identified with abnormal sperm morphology, so this might be related to an increment in mutation rate in the male germline cells which would most likely have a bad side to it, which we happen to observe, since most mutations are deleterious. But that might not be the complete story, there may be a possibility of a beneficial aspect that escaped observation, i.e. a beneficial mutation that might arise from the possibly higher rate of mutation.

see: https://www.medicalnewstoday.com/articles/277543.php

@ZuhairAl-Johar: (psychological) stress at the level of organism doesn't necessarily translate in the kind of cell-level stress needed to produce [more] mutagenesis. At least I don't know of evidence for that link. The article you indicated talks about lower testosterone etc. as the effect of organism-level stress; it's not clear that that has any effect on mutagenesis, and I think it probably doesn't have such an effect.

I don't have access to the review, but are you sure it supports such a broad claim? For instance, we've known for several years that Alu translocation rate is increased in response to heat stress. I am not entirely sure if the OP would include this sort of stress, but still.

@terdon: they don't' mention/cite that paper. They do discuss SIM in some 35 bacteria that it was observed in. And they do acknowledge "large-scale topological" mutation-rate variation in eukaryotes with some examples. I guess they don't think that's SIM enough. I should also mention that this review is marked as "opinion/perspective", so perhaps the journal editors did see it as somewhat biased.

@terdon: of course heat stress is included.

@terdon: you were fairly correct, I should have checked one of the other review (more sympathetic toward SIM) which Lynch was citing. I've rewritten my answer based on that. Let me know if you think it's too skeptical.

Oh wow, that's what I call improving an answer, thanks! That's a much more nuanced position :)

@ZuhairAl-Johar What do you mean by heat stress? The feeling that your surrounding is too hot? Or the gametes being exposed to high temperatures? Because in your examples you describe stress as more psychological state of mind (ex. fear), but in these it's the latter i.e. I believe the cell upregulates or loses regulation of DNA mutation processes in direct response to heat.

@Cell, "stress" can be psychological or organic, thirst, hunger, excessive heat or excessive cold that threats survival are definitely stressors, even psychological stress can cause physiological changes, like hormonal or otherwise, that might cause a stressful conditions on the germline cells. Heat, cold, other stressors need not directly affect the germline cells, it can affect them via hormonal or other chemicals released in response to stress.

@ZuhairAl-Johar That's nice but I wasn't asking for an explanation of what stress means. I was just asking for you to clarify that you understand heat stress means something different mechanistically in lower organisms than what your question is implying (psychological).

@Cell, yes of course they are different, however heat stress in higher organisms need not be mediated via psychological stress, a physical stress can indirectly affect the germline cells through hormonal or other chemical changes without being related to psychological stress from that physical stressor, anyhow this is different form the direct effect of those stressors on lower organisms definitely.

Sure if you say so.


text:
Is this model of understanding of what's natural selection and what's not, correct?
Here in this account I just want to make sure, that I've grasped the concept of natural selection as is usually spoken by evolutionary biologists, truly the wording here are non standard and in some sense sloppy, yet I want to make sure that I've got this concept right.
My account on what constitutes natural selection and what's not:
We say that there is a causal relationship from [A] to [B], to mean that there is a process in which A is a part of, that results in changes in B.
Also we can paraphrase the above by saying that there is a causal relationship that [A] has on [B]; or by saying that [B] is the consequence of a causal relationship from [A].
Now Natural selection seems to require those as prerequisites:

There is a causal relationship from some [hereditary material g] to the [survival and reproductive status of individuals harboring g].

More precisely and incorporating some standard terminology this is:
There is a causal relationship from a [genotype g] to [absolute fitness of g].
We call such hereditary material as fitness related hereditary material.

A variation exists between some fitness related hereditary material as regards their final causal effect on the degree of their fitness in a common environment $E$. Mathematically speaking, this is:

$\exists E, g_1, g_2( E \text { is an environment } \wedge g_1,g_2 \text { are fitness related hereditary material } \wedge g_1 \neq g_2 \wedge fit_E(g_1) \neq fit_E(g_2))$
In English: There exists an environment $E$ and $g_1, g_2$ where both are fitness related hereditary material such that $g_1$ is different from $g_2$ and fitness of $g_1$ in enviornment $E$ is different from fitness of $g_2$ in environment $E$.
Two fitness related hereditary material that have the same final effect on the degree of their fitness (even if through different causal mechanisms) in a common environment $E$, are said to be isofit$_E$, while those that differ are said to be anisofit$_E$. Formally:
$g_1 \ isofit_E \ g_2 \iff fit_E(g_1)=fit_E(g_2)$
$g_1 \ anisofit_E \ g_2 \iff fit_E(g_1) \neq fit_E(g_2)$
Of course anisofit fitness related hereditary material might even have a difference in the direction of their effect on fitness, so a positive direction means that "the causal relationship from the hereditary material to its fitness, is towards increasing its fitness"; while the opposite is for negative direction.
Now for every hereditary material $g$ the population of all individuals in environment $E$ that harbour $g$, is to be called the "$g$ population in $E$".

There is an environment $E$ that has two anisofit$_E$ fitness related hereditary material populations living in $E$.

If we have 1 and 2 and 3, then we can have Natural selection!
The reason is because Natural selection is the differential (i.e., non-equal) size of populations of anisofit fitness related hereditary material, living under a common environment, that is caused by the differential causal relationship those hereditary materials have on survival and reproduction of individuals in their populations under that common environment.
The above serve as a definition of natural selection, albeit a long one, but I think it captures the intended meaning given to that term by evolutionary biologists.
Now from the above definition we get to infer two properties that natural selection has:

Natural selection is always not neutral. Note "non-equal" part in the definition. The reason is because we have two anisofit fitness related hereditary material populations living under a common environment, and the difference in their size is attributable to the effect of those hereditary materials on their fitness in that environment, so since those are aniso-fit, then clearly the size of populations of them would be different.
For the same reason outlined in 1, we expect natural selection to be "co-directional", i.e. the difference in sizes of the populations of those anisofit hereditary materials, must parallel the difference in the effect of those hereditary materials on their fitness in that common environment, so the population with the hereditary material causing "higher" fitness would have the "bigger" size! In other words natural selection increase the size of the population of the hereditary material that causes higher fitness on the expense of the size of the population of the hereditary material that causes lower fitness.

On the other hand suppose we have some environment in which there are two anisofit fitness related hereditary material populations. Now if some environmental, or recombinative genetic change inflicts those two populations, that works either in a neutral manner, i.e. causes equal population sizes of those anisofit fitness related hereditary material, or works in an opposite-directional manner, i.e. in a direction that is opposite of the expected direction mentioned above, better be termed as "contra-directional". In this situation even if the size of the populations of those hereditary materials is different (imparting the appearance of a selection) still that difference is not explained by the effect of those anisofit fitness related hereditary material on their fitness in that environment! So this would not be an example of natural selection! It would be an example of an environmental factor that caused a "genetic drift", or of a genetic recombination process that caused a "genetic drift" also.
So we in effect have a struggle between "natural selection" which works in the direction of increasing adaptation with the environment, on one hand, and "random selection" (or sometimes called neutral selection or non-selection) which doesn't necessarily work in the direction of increasing adaptation with the environment.
So in some sense "evolution" is determined by the struggle of those two kinds of mechanism of change.
If random change prevails, then evolution would not necessarily move in the direction of increasing adaptation of living organisms with their environment. While if "natural selection" prevails, then evolution would proceed in the direction of increasing adaptation to the environment.

This is far too long to be a focused SE question. Individuals who have genetic material that makes them more likely (not definitive, more likely) to survive and reproduce (===fitness) contribute on average more to the the next generation's genetic material.

@BryanKrause, I just wanted to know if there is a serious error with my understanding above. As regards your sentence, it appears to be more compact, but more compact is not always easily understandable.

You have a 12 line long sentence and a 8 line long sentence! This kind of impossibly long sentence make it hard to understand what you mean.

@Remi.b, thanks for drawing my attention to that, I've edited those sentences by breaking them into smaller ones. See again please.

one thing worth mentioning is a gene or phenotype is not unilaterally more or less fit, the fitness is dependant on the environment, a gene that increases fitness in one environment may decrease it in a different one. Even things like what percentage of the population a gene occurs in can affect its fitness, some genes are only adaptive while in the minority. Fitness is highly conditional.

@John, this is a good point! so fitness needs to be defined in a conditional manner, i.e. like saying finitness in environment "E", and not just fitness like that unleashed. However notice that in point 3 I've required common environment!

I see that but this is dependent on how you define environment, an environment is not static, the environment also includes all the other genes in an organism, the other individuals in a population, ect. selection also indirectly changes the environment. So each E is instantaneous, maybe an E prime to designate this.

@John, I think for the purposes of giving a general definition, its sufficient to state "common environment" as such, the specification of which and which environments is a particularization matter, it speaks about particular natural selections, but for the general purpose of a general definition of natural selection , all what is needed is to mention "common environment".

You may want to add the "computational-model" tag, it will draw in more poele who will understand the mathematical structure of your question. Changing your title to include some mention of modeling would help, right now the title is going to draw people with little experince in such an approach.

I've mostly skimmed the formalism you introduced, but getting to the 2nd half of your post, the answer is yes, you understood correctly the distinction between natural selection (aka adaptive evolution) and drift (aka neutral evolution), as well as the fact that it's not a given that natural selection would be the predominant effect in arbitrary circumstances. Small population sizes, high rates of mutation, weak genetic repair mechanisms, etc. can all lead to chance being the predominant effect.
The conditions needed for natural selection to be predominant have been investigated in lots and lots of publications. A quick overview and brief list of such publications is found in

Duret, L. (2008) Neutral theory: The null hypothesis of molecular evolution. Nature Education

One final point I'll make here is that we need to be careful to define what we're talking about being selected. In general, for phenotypes there's not much debate that adaptive (rather neutral) evolution dominates in nature. The research and debates mostly concerned what happens to genotypes. This is somewhat obvious since there are numerous mechanisms that mediate the translation from genotype to phenotype.
A departing teaser, there's still a lot debate concerning how the mechanisms that enable low-error genetic transmission (the surpassing the famous error threshold) came about in the primordial soup. One interesting adaptation we can observe today is that bacteria can alter their rate of mutation in response to environmental changes; they function a bit like the Hulk superhero does: if you stress them, bacteria mutate faster (aka stress-induced mutagenesis).

And to save you from rediscovering a certain wheel (and posting it here), in the biologically-inspired (but not biologically faithful) realm of "genetic algorithms", there's "fundamental theorem"  (of Holland) that states under what conditions (in that simplified world) [natural] selection is likely to be the source of high-fitness schemata (an equivalent of well-adapted genotypes). But the theorem doesn't exclude that such schemata can simply appear by mere chance mutation.
More generally, there's the Price equation; it partitions total evolutionary change in that due to natural selection and that due to other causes (including transmission changes, like mutation). However, without additional assumptions, this is as good as it gets. To quote from SA Frank:

No general conclusion about total evolutionary change is possible, because the complete range of forces that can perturb populations remains unpredictable. However, we can express an elegant equilibrium condition. At equilibrium, the gain in information by [natural] selection must be exactly balanced by
  the decay in information caused by other evolutionary forces.

In the simplified world of genetic algorithms, such additional assumptions are made (e.g. there's a specific transmission model) a point that is missed (IMHO) by people who diss Holland's theorem as merely restating the Price equation.
And I should at least name-drop the Wright–Fisher model which seems to be the most studied by those interested in a closer approximation of biology (as opposed to solving optimization problems, which is the goal of genetic algorithms). The Wright–Fisher model also makes specific assumptions about transmission; it seems a lot variants of it have been investigated. On this model and a lot more, see chapters 1, 6 & 7 in Durrett's book Probability Models for
DNA Sequence Evolution.
Anyway, my main point in this second half of my answer is direct you to well-known formal treatments of evolution by natural selection.

Thanks, I think there is a typo, you said at the 16th line.........natural (rather than natural)....I think you meant (rather than neutral)

Quote: "In general, for phenotypes there's not much debate that natural (rather than natural) selection dominates in nature".

@Fizz AFAI, "Neutral selection" is not a concept.

@Remi.b: fair enough, it's an abuse of language, so I've replaced it with "neutral evolution", which is more widely used, although... https://arxiv.org/abs/1211.3609

@Remi.b: Or... https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=%22neutral+selection%22&btnG=


text:
Antibiotic resistant genes
Can someone help me find be it an article or journal that has the conventional PCR method for the detection of antibiotic resistant genes?
Thanks in advance.

Do you have in mind any specific antibiotic resistence gene? Which antibiotic?

I tested my isolated bacteria against 10 antibiotics, namely: Tetracycline, vancomycin, cephalothin, ciproflaxin, chloramphenicol, ampicillin, erythromycin, kanamycin,trimethoprim, and neomycin.