text:
What proves that speciation is a pairwise process?
I have been asked this questions by many biology students and even non-biologist without a pretty straightforward answer to give. We are quite accustomed to phylogenetic trees where a common ancestor becomes two different species and these new species become, each one, two more. But, Why is not possible that a species might divide in three different species? Or four? Or more?
What arguments support this conception of the evolutionary process? Also, if somebody has a good article explaining this, please provide me with the link or citation so I can refer my fellow biology students to it.

Speculation: consider what tends to cause speciation — either some barrier (fully or partially) divides a population, or a selective pressure favours different extremes of a group.  With each of these, speciation will be binary unless two such barriers or selective tensions arise simultaneously.  So you’d expect it to be unusual for that reason, but you can also imagine situations which would cause it, e.g. a large flood wipes out most of a population (of a sedentary species), and the remnants form three or more isolated groups.

possible duplicate of Does a fully-resolved phylogenetic tree have to be dichotomous?. See also Evidence & discussions of hard polytomy

I offer this perspective in addition to what WYSIWYG has provided.
Phylogenetic trees are tools to model what has actually happened, or what some evidence implies has happened, to a population of entities that exchange genetic material.
These models fail, for instance, when describing the phenomenon of horizontal gene transfer since a tree is acyclic by definition. Consider a viral genome that has integrated into a host genome. The host now contains DNA from its ancestral lineage and the viral lineage. This process cannot be modeled by a tree.
Some founder population that is susceptible to exogenous genetic transformation may give rise to many distinct lineages, some of which your species concept may qualify as "new" species.

+1 This is an important point. I wonder what can be commented about this case in which a virus integrates in two different locations in two different individuals of a population and this leads to phenotypic differences between them (a sort of speciation). This also qualifies as a case of two species coming from one because of anisotropic horizontal gene transfer.

It is not impossible that a species can give rise to more than two lineages simultaneously, but it is just highly unlikely in certain cases.
If you assume that a point mutation in the DNA gives rise to a lineage then the number of two different mutations happening simultaneously (in two different individuals from the population) and also getting fixed, would be low for a small population. In any case a single DNA won't give rise to two different mutants. However this number would increase with increase in population size.
In such cases (small population) two separate events can be assumed rather than a single event that gives rise to two mutants. However, if the time difference between the occurrence of these two events cannot be determined (or it is too small compared to other timescales) then a single event can be assumed.
Phylogenetic trees can have nodes with multiple branches if the distance between all of them is the same (as in the abovementioned example; the distance between all of them is 1).
So I think it can be said that the likelihood of simultaneous formation of multiple lineage increases with population size.

I agree that the total ordering of events that give rise to new species (lineages) would give a total ordering to the branches in the tree or graph representing the speciations. The last statement may be true only if the probability of speciation-event-mutations increases with population size, like in the case where it were equiprobable and non-zero for all individuals.

@mcg256 The likelihoods actually won't change. But the number of mutants will increase with bigger population.


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Is probability for double crossing over included in distance cM? [task]
We got this task:
There are 3 genes (acb) on one chromosome (linked inheritance). Distance a-c = 12cM, a-b=16cM. Probability for double crossing-over (CO) is 0,6%. Find ratio of genotypes of descendants (AcB/acb X acb/acb).
I don't know whether the 0,6% for double CO is included in the 16% (16cM) probability.
I think it is not, so I got these ratios:
No CO and double CO: 42% AcB/acb, 42% acb/acb,
1x CO: 8% Acb/acb, 8% acB/acb

Centi-Morgan (cM) is based on observation not precise measurements. Now since double crossing-overs (and actually any arbitrary even number of crossing-overs) revert gene combination to the parental type, resulting lower recombinant frequency. So in your case since the chance (or the frequency if you wish) for double COs is 0.6%, you have to subtract this from parental genotypes and add it to the recombinants.

source: Stack Exchange

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sort: votes


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Why is hyper pigmentation the common aftermath of skin lesions and abrasions?
I'm aware that melanocytes produce melanin, giving color to the skin, but why are these cells recruited or overactive when healing skin abrasions, lesions and sores when T-cells and inflammatory cytokines of the immune response help with healing. I'm just wondering why the production of color is associated with the healing of the wound and if it proves beneficial, or if it just a side effect so to speak.
EDIT: In this study, it explains the recruitment of melanocytes after the initially response of innate immune cells and inflammatory cytokines, however, it does not delve into how this is beneficial to the cell.
[source]

It's considered a requisite on biology.se that at least some research is carried out and presented with your question. Otherwise it will be closed as homework. What other cells are involved in skin healing? Certainly more than white blood cells. The site tour and the help center  provide guidance on how to use this site.

I am not fully aware of the details now but I know that IFNγ signaling is involved at some step in the regulation of pigmentation.

The upper layer of the skin (or the epidermis) is formed mostly by keratinocytes and some melanocytes (about 30-40 times more keratinocytes) and also fibroblasts (although they are not shown here). The melanocytes are found in the basal cell layer at the border between epidermis and dermis as shown in the figure below (from here):

The melanocytes spread out their dendrites between the keratinocytes and transport the melanosomes (pigment containing vacuoles) to them to pigment these cells. This is a highly regulated process and depends strongly on the interaction between keratinocytes and melanocytes.
In the so-called paracrine pathway the keratinocytes secret substances which regulate the production of melanin. These are for example alpha-MSH or ACTH, which stimulate the melanocytes to produces more melanin.
This regulation is the key to the hyperpigmentation. During the proliferation or the inflammation chemokines and hormones are produced (and secreted) in the skin which stimulate keratinocytes and fibroblasts. These are for example the keratinocyte growth factor (KGF), as well as the chemokines IL1-alpha and TNF-alpha. This stimulation leads to the production of ACTH (and derived peptides) by the keratinocytes and the secretion of stem cell factor (SCF) and hepatocyte growth factor (HGF) by the fibroblasts which all induce pigmentation. The chemokine secretion is also enhanced from the keratinocytes by KGF. If you are interested in a deeper view at this topic, have a look at reference 1 (and the references in the paper). Reference 2 goes deeper into the regulation of the paracrine signalling.
In an injury (especially in larger areas of the skin) a lot of cells are damaged and need to be replaced. This functions via cell division but also via the migration of cells into the affected area. This is described by the paper you link - here melanocytes and melanoblasts (melanocyte stem cells which can divide and then differentiate into melanocytes) migrate into the injured region to replace the destroyed melanocytes.
References:

Mechanisms underlying post- inflammatory hyperpigmentation: lessons
from solar lentigo
Hepatocyte Growth Factor Establishes Autocrine and Paracrine
Feedback Loops for the Protection of Skin Cells after UV Irradiation

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Non Coding DNA and its effect on evolution
I had a discussion with a friend of mine; from his understanding, bacteria and other small organisms have higher amounts of "coding" DNA and, as such, are able to evolve much faster than organisms like us.  His argument was that if bacteria are able to evolve so much faster than us, then they should have become the Apex Predators on Earth instead of humans.
I argued that the 2% of the "coding" DNA is probably as long as the 90% of a bacterium (I'm guessing at this point) and that it is the bacterium's small life span that makes it evolve so fast.  Was hoping to get clarification from someone with more experience in the field.

Well, your friends argument does indeed make no sense, which makes it kind of difficult to address. Evolution tends to drive populations to become better adapted to their environment. That in no way implies that faster evolving organisms are at the top of the food chain. Bacteria can evolve faster largely because of their short generation time.

You can do a crude calculation about the amount of coding DNA in humans based on your 2% figure. The human genome is ~3.2 Gb. 2% of that is 64 Mb. Compare to the E. coli K12 genome which is about 4.6 Mb.

I've heard the suggestion that DNA is encrypted as a protection against virus. Maybe someone knowledgeable here can say whether this is a serious possibility?

DNA isn't encrypted...

Generation time is indeed the correct answer. On top of that some bacterias do exchange genetic material (like antibiotic resistance genes) via "plasmids" and therefore can adapt even more quickly.

I reject the premise that apex predator is the pinnacle of evolution.  Filter feeders like humpback whales only survive because plankton greatly outweigh them.  Doesn't that make them, as a class, more successful?  Whales might go extinct in the near future,  but not phytoplankton.

Richard Dawkins discusses this in his book The Greatest Show on Earth: The Evidence for Evolution
Bacteria and other microorganisms, specifically Archaea, are able to exchange in a sort of 'copy and paste' genetic exchange that differs wildly from sexual reproduction.  They can even exchange genes with other distantly related species.  This, coupled with their short (compared to Humans) lifecycle, accounts for much of the difference in evolutionary rates.  Often, it makes sense to speak in terms of evolution in terms of specific genes themselves (in the case of bacteria), as opposed to evolution of the species as a whole, due to the 'copy and paste' exchange that can take place.  For Bacteria, there is something to be said for compiling a 'true' family tree for each gene separately, regardless of which kind of bacteria in which it resides.
Dawkins remarks, "The philosopher Dan Dennett has put it, 'Where the tree of life for animals is a majestically spreading oak, that for bacteria is more like a banyan.'"
Also, evolution by Natural Selection and random mutation does act on 'non-coding' DNA, just to be clear.

http://www.livescience.com/46986-human-genome-junk-dna.html
Microorganisms are often able to adapt to new environments quickly, but they lack the specialized functions of macro-organisms. Consider that the micro-organisms of macro-organisms have developed to form machinery that builds solutions to problems, rather than being retrofitted themselves to counteract new threats. Each time a bacteria needs to adapt itself to attack, whereas the specialized cells of our body can manufacture a solution on the fly rather than waiting around for a random beneficial strait to show up in the population. It would be like a small manufacturer quickly retrofitting it's production system to produce a new product. Sure, it can produce a new product, but it takes time for setup, and the company can only produce a limited number of varied products at a time, whereas a giant production company may have a huge amount of preset equipment for manufacturing a enormous variety of products with no need for retrofitting (evolution). The larger factory could have the advantage when it comes to efficient production, with quicker turnaround.
Therefore, the specialization of micro-organisms leads to nature allowing the evolution of macro-organisms as the major factories of nature.
Excess, unused (or at least non-critical) DNA is useful because it allows evolution some wiggle room. If a bacteria suffers a deleterious mutation in a vital gene, then it's obviously not fit. But, that same bacterium with can accumulate potentially useful codes in the previously unused portion of it's genome, without needing to deal with risky mutations in vital genes. And again, as microorganisms specialize, they can fabricate new proteins and such, with lower risk, and less time, compared to micro-organisms which use evolution of their genome as the sole/primary means of short term adaption.

This is not exactly correct.... non coding DNA is not "unused" as you said. Several studies have proven that non coding DNA, in most cases, is in fact regulatory DNA, origins of replication, centromeres, telomeres, etc.. Sources in case you're interested: http://www.theguardian.com/science/2012/sep/05/genes-genome-junk-dna-encode, http://en.wikipedia.org/wiki/Noncoding_DNA, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2884187/

I assumed by the word "non-coding" that they meant sequences which are truly responsible for nothing. There are obviously going to be sequences that do nothing, or do something which has a completely neutral effect.

Also, there is an issue with the idea that all the genome is being used: http://www.livescience.com/46986-human-genome-junk-dna.html                                                                                The human body is pretty complex compared to wheat. Yet wheat has 5 times the amount of information? That can't possibly all be regulatory and such.

@CDB
Consider the very first organisms. They must have had SOME non-coding DNA which served no purpose, otherwise they would have had no room for growth, with each mutation destroying something critical to the function of the cell. It's VITAL that there be junk DNA initially, and after life has gotten a foothold, junk DNA can offer a competitive advantage for the reasons stated in my answer. So nature clearly has a reason to select for organisms which have non-functional and/or large amounts of non-critical information. Telomeres can shorten, and still fulfill their role.

@CDB
A mutation which extends a telomere, also allows for further mutation of potentially beneficial traits within the telomere, with less chance of destroying it's function.

Perhaps it would be better to use the term junk DNA rather than non coding DNA than, seeing as most non coding DNA actually does do something. I just wanted to clear up a term that many people get wrong. As for the wheat, it's large genome comes mostly from it's many ancestors. And yes, most of that %80 non coding DNA is regulatory and such. But you are right, not all of that is vital, but there is only a very small percentage that is actually junk. Like I said, I just wanted to clear up that term.

@CDB The article I just provided states that "80%" is NOT regulatory. Take a look at introns: en.wikipedia.org/wiki/Intron Introns are coded for, but removed. SOME do NOTHING because they aren't given a chance to do so.

I was talking about wheat. Umm....introns do quite a bit, where are you getting all this?

Introns often do something. However, intron loss and gain would not be possible if they were always required or served a function. Eventually, you will have sequences which pop up and do absolutely nothing for at least a time. They do no harm, and they do no good. They simply go unused.

I never said it wasn't possible to get unused sequences, I merely wanted to clarify the misused terms to avoid confusion.

Oh...I thought you were saying unused code was not possible...nvrmind. My earlier comment was meant to be "Also, introns...", to imply a new offshoot...


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Are there some natural instances of thermosensitizer?
Let's define thermosensitizer as any chemical or biological agent that can sensitize the cells to heat. In lab setting, thermosensitization seems to be achievable, such as by inhibiting chaperone activity.
I wonder if in nature there are some instances of thermosensitizer? Specifically, the question is not concerning the various regulatory mechanisms of the cells to survive heat. It's more about if some organism can exert/secrete chemicals on another organism to make the latter more sensitive to heat, for example in self-defense or for killing.

Geldanamycin/radicicol would be examples. They are both Hsp90 (protein chaperone) inhibitors. There is a lot of literature on their biological effects (see references therein), specifically their role modulating genetic interactions and also as chemotherapeutic agents for killing cancer cells.
Both of these natural compounds are created by microbes as antibiotic chemicals for interaction with other organisms.

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"Acellular" designation for organisms
Why do some biologists refer to single-celled organisms such as Amoeba and Paramecium as
acellular (i.e., without cells) rather than unicellular (i.e., one cell)?

Can you point us to an example of this?

From Wikipedia:
Some biologists refer to wholly syncytial organisms as "acellular" because their bodies contain multiple nuclei which are not separated by cell walls.
As Albano pointed out, "cell walls" should probably be "cell membranes".
Paramecium and some types of amoeba like the Chaos genus have multiple nuclei so they fall under this definition.

Our own cells are not separated by cell walls either. This is an error in Wikipedia. It should probably read "cell membranes".

@S.Albano yes you are right it should probably be cellular membranes.

@Bitwise, I stand corrected thank you. Comment removed to avoid confusion.


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How can synonymous mutations lead to cancerous or tumorous phenotypes?
After analyzing DNA sequences of an oncogene from many human cancer patients, you found that synonymous substitutions occur in a specific codon of this oncogene. Assuming that these synonymous substitutions do not exist in normal populations but do contribute to tumor development, what would be possible mechanisms that would explain how such alterations can lead to tumor phenotype?

Can you finish the title of the question?

What are your ideas regarding this question? Have you thought about any possibilities?

I think you assumed that synonymous mutation means silent mutation. But this is not correct.
From Wikipedia (synonymous mutation) :

Synonymous substitutions and mutations affecting noncoding DNA are often considered silent mutations, however this is not always the case. Synonymous mutations can affect transcription, splicing, mRNA tranport, and translation, any of which could alter phenotype, rendering the synonymous mutation non-silent

From wikipedia (Oncogene):
The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:

A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing

an increase in protein (enzyme) activity
a loss of regulation

An increase in the amount of a certain protein (protein concentration), caused by

an increase of protein expression (through misregulation)
an increase of protein (mRNA) stability, prolonging its existence and thus its activity in the cell
gene duplication (one type of chromosome abnormality), resulting in an increased amount of protein in the cell

A chromosomal translocation (another type of chromosome abnormality)

There are 2 different types of chromosomal translocations that can occur:

translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
translocation events that lead to a fusion between a proto-oncogene and a 2nd gene (this creates a fusion protein with increased cancerous/oncogenic activity)

the expression of a constitutively active hybrid protein. This type of mutation in a dividing stem cell in the bone marrow leads to adult leukemia
Philadelphia Chromosome is an example of this type of translocation event. This chromosome was discovered in 1960 by Peter Nowell and David Hungerford, and it is a fusion of parts of DNA from chromosome 22 and chromosome 9. The broken end of chromosome 22 contains the "BCR" gene, which fuses with a fragment of chromosome 9 that contains the "ABL1" gene. When these two chromosome fragments fuse the genes also fuse creating a new gene: "BCR-ABL". This fused gene encodes for a protein that displays high protein tyrosine kinase activity (this activity is due to the "ABL1" half of the protein). The unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which can cause a cell to grow and divide uncontrollably (the cell becomes cancerous). As a result, the Philadelphia Chromosome is associated with Chronic Myelogenous Leukemia (as mentioned before) as well as other forms of Leukemia.

You might be especially interested in the second point (An increase in the amount of a certain protein)

Therefore, there is nothing impressive to find some synonymous mutations that are involved in oncogenes.

This paper here talks about how synonymous mutations are over-represented in oncogenes and cause mis-splicing of the gene.
http://www.sciencedirect.com/science/article/pii/S0092867414001457#bib22
In addition to that, synonymous mutations could also work by affecting a regulatory region like a transcription factor binding site, enhancers, etc., leading to enhanced or decreased expression of the corresponding gene.


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How does life change when you dig deeper?
I've just realized that I have no idea what life / biotopes / soil looks like when you dig deeper than a few meters.
I know that in the first meter of soil you can find all sorts of live animals (like moles and rabbits), insects (like ants, but many more), plants, and single-celled organisms, of course.
But how does that change when you get to the depth of a metro station (below 30m)? When you plan to build a metro, do you have to consider that you might destroy a biotope?
I guess there is a point from which you will quite certainly not find animal/plant life in the soil anymore. This will, of course, depend on where exactly you are. But can you give a rough estimate of how deep we're talking? 50m? 100m? 1km?

With a quick search I found 'Subterranian worms from hell' in Nature. The worms were discovered in a gold mine over 1km deep.

Extremophile bacteria and archea are living very deep beyond our imaginations. This is what you need for general composition at different depths. And this and this is for the deepest living organism known ! Following is image from (Manson et al 2010) which shows at what depth you will get bacteria

Even more deeper, Wold's single species ecosystem, Desulforudis audaxviator which can be found 3 km below sea level.

"Soil horizon" was what I was looking for. Thank you!

First of all we must consider what the substrate is at 30 meters and deeper, either clay, anaerobic, impermeable or permeable substrates, everywhere that you find liquid water between 0-100 degrees you find life (Geogemma barossii reproduces at 120'C 250'F), even if the peak of everest is mostly under zero and has 270kph winds, algae grows there.
Plant life requires light, so you will only find roots underground, the deepest roots are an african fig that has a record of 120m 400ft. Most plants have roots that can go as deep as the tree is high in permeable ground while clay soil is very low on oxygen and voids for anything to infiltrate. Underground mining will rarely affect tree roots, or any other notable biotope, unless it encounters a rare cave system with fish and so on.
In very deep caves 200 meters deep there can be all kinds of insects and fish, although that doesnt qualify as ground.Krubera cave georgia has insects at 1.5 kilometers depth.
The solution of the question is that of matabolism, anaerobic versus aerobic, and it's effects on biotope richness. Funghi breathe and bacteria can be anaerobic, so they are the deepest, you can find some in oil wells and 1.6km under the sea floor.
The major concerns for drilling and damaging deep biotopes are from mining isolated aquifers with endemic animals, for example the deep lakes of antarctica that have been set apart from the rest of the world for 10's and 100's of thousands of years.
The ecosystem richness of zones without light and oxygen and flowing water is generally too low to foster much attention from any environmentalists and conservation organisations, it's also not a rare biotope.


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Why did many odd-toed ungulates become extinct?
There were a lot of odd-toed ungulate animals in the ancient times but now just few of them survived. What is the reason for that?

I edited the question somewhat. You need to provide some more details such as how many/what fraction of odd-toed ungulates got extinct. Compare it with other group such as even-toes ungulates. Because a lot of species perish during selection event. When saying a lot of group-A organisms perished you should mention with respect to what?

there are two suborder under perissodactyla that are still suvival, Hippomorpha and Ceratomorpha. many perissodactyla species become extinct may bacause the member of perissodactyla animals have sample stomach, compared with artiodactyla, so after the plant change on the earth, they cannot adapt it. and also hinting was one part of reason.
http://en.wikipedia.org/wiki/Odd-toed_ungulate

If you downvote an answer (or question for that matter) please leave a comment with an explanation. Users cannot improve their posts without some feedback.

@user137 I am not downvoting but I have to admit that the answer is grammatically wrong, badly linked and hard to understand


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Duration of selection and survival of the fittest
I feel there is a part of the theory of evolution I'm not understanding correctly or maybe I'm missing it, but would like cleared up.
From what I understand, over time random mutations occur which in some cases provide an advantage allowing that animal to survive and reproduce. Its children will have that mutation allowing them to survive and so on over many many years until it evolves into a new species and / or the old ones become extinct.
For example the rock pocket mouse.
The part I'm getting stuck on is that unless these mutations happen instantly and in a large number, given its over such a big time scale how do animals who are not well adapted get enough time to evolve to survive?
Another example is fish that evolve to be able to "walk" out of the sea to escape predators.
If moving out allowed them to survive how did they get enough time to evolve and not be made extint in the time they didn't not have these limbs.
Hopefully I have explained myself clearly :)

Could not fit in a comment..
Welcome to Biology.SE! Here are a bunch of comments.

The sentence until it evolves into a new species and / or the old ones become extinct sounds weird and there seems to be some confusion between evolution and speciation. Also it seems that you have a very static view of what is a species, as if species were predetermined categories into which evolution came to show itself!
I am not sure but I think your question has to do with "valley crossing", that is "how can a population evolve toward some phenotypic trait if intermediate phenotypic traits are not fit?" Is that your question? You may be interested in "shifting balance theory" but it might be a bit too advanced.
It is common to overconsider the valley to cross (the deleterious impact of interemediate traits) and those traits are not necessarily so deleterious
Mutations do not always have small effects on traits. One mutation may have some very important impact and therefore, one mutation alone might be enough to cross a whole valley! You amy be interested in Fisher's geometric model. Fisher's geometric model is just some very arbitrary model and is not much inspired by any biological observation but it helps getting the concept of how mutations impact fitness (=function of survival and reproductive fitness).
When you say how do animals who are not well adapted get enough time to evolve to survive? I may use the word animals to refer to populations or to individuals in a population (extinction of genotype is a population and extinction of populations are two different things). If you referred to individuals then, your interest seems to be into "valley crossing" and "mutational effect"(effect of a mutation on phenotype or fitness). If you referred to populations, then you may be interested in "evolutionary rescue" or more broadly speaking in the so-called "theory of extinction".
There are probably other posts (or part of answers) on this site that will help you. A very good answer would be very very long. But maybe a moderately good answer may be relatively short!

From what I understand, over time random mutations occur which in some cases provide an advantage allowing that animal to survive and reproduce. Its children will have that mutation allowing them to survive and so on over many many years until it evolves into a new species and / or the old ones become extinct.
The part I'm getting stuck on is that unless these mutations happen instantly and in a large number, given its over such a big time scale how do animals who are not well adapted get enough time to evolve to survive?

You are quite confused about what is evolution!
The idea is not at all that all the individuals of a population will acquire the same change and become another species.
One individual gets a beneficial mutation and thus reproduces faster than others. So this mutation spreads little by little in the population because eventually only descendants of the first individual bearing the mutation will remain.
This is what is called a selective sweep. But it has nothing to do with the concept of species, which involves much more complex processes.


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Supercomputer and undergraduates
Is it common for an undergraduate to run their thesis (evolutionary genomics) in a supercomputer? In my country, few supercomputers exist, but I'm not sure how it is for bachelors in the US or Europe. I am writing my application to graduate school abroad and I want to know if it is a remarkable point I can use as hook to begin my statement.

This question would be better suited for academia SE.

If there are no pending jobs then you can use it. Why do you need supercomputer for. In any case this question is off-topic

This question appears to be off-topic because it is not about biology

IMO irrespective of country and level (undergrad/Masters), if you can run a job on a High Performance Computing cluster or a supercomputer, you should mention that on your resume. And sure, you can use that in your statement, especially given the fact that not many have access to it, you had the rare opportunity and made full use of it.
In my experience, I haven't seen many undergrads here in the US that can run a job on a HPC - not without prior computing experience!
All the best to you!


text:
Aligning multiple sequences in heterogeneous group
I have a list of ~200 DNA sequences, representing probably 50 different genomic regions but they're all mixed up. For example, if I have seq1, seq2.... seq10, seq1 might align to seq3 and seq8, but be completely unrelated to the others.
There are also some differences in the lengths sampled, so the above example might represent:
Seq1-------------------------------------------------
Seq3----------------------   seq8-----------------
Such that seq3 and seq8 don't align to each other, but both align to seq1
So what I'd like to do is go through and somehow generate a list of groups of sequences that align to each other, as well as the alignments. eg:
Group 1
Seq1-------------------------------------------------
Seq3----------------------   seq8-----------------
Group 2
seq2------------------------------------
.       seq6-----------------------------
.   seq7--------------------------xxxxxx
Group 3... etc
Trying ClustalW or MUSSLE to align everything doesn't work (or takes an unreasonable amount of time), I'm guessing because there are so many sequences that don't align at all. I tried making a custom BLAST database and then BLASTed each sequence against it, but then I get multiple hits for the same alignment (with the group 2 example above, seq2:seq6, seq2:seq7, seq6:seq2, seq6:seq7, seq7:seq2 and seq7:seq6 all get returned as 6 unique hits, when they should be grouped together.
My current coding knowledge is fairly basic, but I'm willing to read docs and figure stuff out, I just don't want to reinvent the wheel.
Edit2:
Really, the grouping is the important part - once I have the groups, I can do the alignment separately with little effort. I'd just like to have groups where each sequence is in a single group.

You can try this:

BLAST each sequence to every other sequence (pairwise).
Every alignment (with some defined cutoff) denotes a connection.
Map all connections.
If a sequence is connected to some other directly or indirectly, it falls in a group. Put all the sequences that seq1 aligns to, in Group-1, then go to the alignments of these sequences; put all the sequences that these align to again in Group-1; so keep populating the group like this.

Methodology:

Install standalone blast (if you don't have many sequences then you can run online BLAST as well)
Make a blast database from your sequences using makeblastdb
Align these sequences against the database. If you are using online BLAST use BL2seq (align two sequences). It is much better and convenient to use standalone. You can also mention if you want plus-plus or plus-minus or both alignments. You might in some cases want only either of the two.
In the standalone BLAST you can specify the output format (which fields to include etc- the format you choose just depends on your requirements).

A tabular output format looks something like this:
# BLASTN 2.2.27+
# Query: TCONS_00036712 gene=XLOC_017996
# Database: ../nt_db/nt
# Fields: query id, subject id, % identity, alignment length, mismatches, gap opens, q. start, q. end, s. start, s. end, evalue, bit score
# 1014 hits found
TCONS_00036712  gi|191174875|emb|CU655970.6|    95.54   202 9   0   423 624 16680   16479   8e-85    324
TCONS_00036712  gi|51491599|gb|AC144709.2|  95.02   201 10  0   424 624 28443   28243   1e-82    316

Ignore the commented (#) lines; the first field is query ID, the second is the subject ID and there is an alignment between the two; the other fields provide information about the alignment (You can choose these fields).
For parsing I use a fast and easy scripting language called awk which is included in all UNIX based systems. It is also available for windows in GNUWin32 package.
What you have to do is check the first two fields and update the group.

# MakeGroups.awk

BEGIN{FS="\t"}     # Declaring Field separator as Tab

!($1 in grp){          # Check if the seq is a parent group. If not...
    k=1
    for(i in grp){
        if($1 in grp[i]){    # Check if the seq is part of any other groups
            parentgrp[$1]=i
            if(!($2 in grp[i]))   # Check if the second field i.e subject already present in the parentgroup
                grp[i][$2]        # if not assign the second field to the parent group
            k=0
            break    # stop checking further
        }
    }
    if(k==1)        # There is no parent group with this label and the seq is not a part of any other group
        grp[$1][$1] # Make a group with the query-id as the label and add this query to this group.
}

$1 in grp{
    if(!($2 in grp[$1]))
        grp[$1][$2]    # If the second field is not a part of the group with first field as label then assign it to that
}

END{
    for(i in grp){
        x++
        print "Group-"x"\n----------"
        for(j in grp[i])
            print j
    }
    print "\n"
}

Run this script like this in the terminal:
gawk -f MakeGroups.awk blastalignmentfile.txt
Note: This script contains multidimensional arrays. It will not work with all versions of awk. Use gawk version >4.0.
As swarnbes mentions in their answer, there are faster algorithms which do this kind of stuff and are used for sequence assembly. What many of them do is to make a graph (networks called deBruijn graphs), where each connection is an alignment, and compute an Eulerian Path. See this review by Pavel Pevzner for details. Overlapping sequences form contigs and you can easily trace back which sequence came from which contig (which you can call a Group). Each contig/Group is a disjoint deBruijn sub-graph.

Yes, though if you can even just point me in the right direction, that would be great.

@kevbonham This script should work. If you like some other programming language you can implement this logic in that.

Wow, thank you very much! This seems like it should work... I might attempt to re-write in python (since that's what I'm most familiar with), but the logic is easy enough to follow. I suppose I would add another loop to ignore matches < a certain % match, or would you specify those parameters in the initial BLAST parameters?

@kevbonham you can add that condition along with checking if the second-field is in a group or not no need to add another loop. Basically all those criteria is to be stringent about the relationship between first and second field. Thing with awk is that it stream reads (doesn't load the entire file in the RAM) and field separation is an easy job. Good for text parsing.

Makes sense. Is stream reading equivalent to something like readline() declared explicitly in python?

@kevbonham readline() reads the entire file line by line and stores it as a list. In stream reading one line is read and the code is implemented on it before proceeding to the next line. To implement stream reading in python use for line in file:. See here. Awk by default does stream reading. Awk also has good regex base; in python you have to import re. Having said that Awk is not as versatile as python but good for certain tasks.

@kevbonham in awk you can specify what the record separator is (RS, which is newline by default). You can instead set ">.*" as the RS for a fasta file and each nucleotide/protein sequence will be read in a stream.

@kevbonham Another point: the equivalent of associative arrays of awk (hashtables) in python is a dictionary. Dictionaries are sometimes very convenient and work much faster than lists.

I finally managed to make this work in python, using your script as a template (at least what I understood of the logic behind it). It's probably far more bloated than it needs to be, but it was a good learning exercise. Is it appropriate to post my code as an answer to this question as a reference? I'm still not completely sure about stackexchange etiquette.

@kevbonham Yes you can do it but this should not be about writing codes in general and this is not the right forum to delve into programming details. Code that explains an algorithm is fine. Pseudocode is better. Codewriting comes under the domain of StackOverflow.

Do you really need BLAST?  That is, are the sequences different enough from each other that you need an algorithm that looks for large differences between them?
Maybe you could use something like Phrap, which should put together contigs for you, if the sequences which should go together are very close to identical.

Well, not exactly. Where the sequences overlap, they overlap with >99% identity, but there might be flanking sequences that don't overlap. I changed up the question a bit to clarify (I hope).

Not sure if Phrap itself would work because it's built for sequence assembly, but the related cross_match or SWAT might work... will look into them a bit more


text:
Doxorubicin's intercalant and topoisomerase inhibition in leukemia?
I am thinking the role of doxorubicin's pathways in cancers such as leukemia and lymphoma:

topoisomerase inhibitor and inhibit DNA activity
intercalant - intercalant DNA bases and inhibit DNA activity

I am interested in which of these mechanisms are most relevant in leukemia and lymphoma.
How does doxorubicin work in leukemia and lymphoma?

isnt it just case of chemotherapy, that is treatment directed to block cell proliferation thus stopping progression of cancer?

I think you are right! It seems that it is not used without chemotherapy? At least this is right: Used in Combination Cancer Chemotherapy: Leukemia, lymphoma, solid tumors, soft tissue carcinomas. Please, make your comment an answer.

I need to search literatures to answer this. What I know is the first explanation about the mechanism is that it works as an intercalator perhaps because there was not much knowledge about topoisomerases at that time. However, DNA fragmentation was described at the same time. I think interacalators themselves do not have abilities to fragment DNA. It is easier to come up idea that topoisomerase inhibition would be responsible for DNA fragmentation. Having said that, I do not have any knowledge to deny contribution of intercalating effect for anti-cancer effects.

@Masi that is chemotherapy. Chemo is a cocktail of drugs

Doxorubicin is part of chemotherapy drugs. Most of them are targeting proliferation of cells, e.g. by blocking cell division or DNA replication.
Intercalants and topoisomerase inhibitors are powerful in interfering with DNA replication (not DNA activity). Other chemo drugs might inhibit proper operation of cell division machinery, such as through interfering with cytoskeleton functions.

What do you think role between intercalation and topoisomerase inhibition?

I do not have the complete answer, but the links below could be useful.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748742/
The article above says etoposide, which is top II inhibitor and effective against cancer, is not a intercalator.
http://www.ingentaconnect.com/content/ben/cpd/2001/00000007/00000017/art00004?crawler=true
You would find the description below in the article. I just quote their description here.
"As with many other DNA intercalating drugs,
topoisomerase II-dependent DNA cleavage is
thought to be the critical event responsible for the
anticancer activity, [101] whereas free radicalmediated
DNA cleavage is probably more closely
related to the cardiotoxic side effects [118]."
http://www.degruyter.com/view/j/aiht.2013.64.issue-4/10004-1254-64-2013-2371/10004-1254-64-2013-2371.xml
The chemical, MLN944 (XR5944) described in the link above was designed as Topo inhibitor, but the topo inhibitory effects were less regardless of anti-tumor activity.
There is another type of anti-cancer drugs intercalating into DNA: cisplatin. Interaction of DNA with cisplatin result in formation of DNA adducts. Therefore, it may be difficult to explain anti-cancer effects by only intercalation. For the reference of cisplatin: http://en.wikipedia.org/wiki/Cisplatin

Doxorubicin and etoposide are both inhibitors of DNA topoisomerase II.
When chromosomes replicate as a cell divides, the helical nature of DNA results in the daughter molecules being tangled up (catenated).  Topo II is an amazing enzyme; it binds to DNA, cuts a gap in both strands, and then passes another DNA molecule through the gap.  Thus it untangles DNA.
If you inhibit Topo II, two things happen.  Firstly, the inhibition usually takes place after the first DNA molecule has been cut.  Thus inhibiting Topo II causes severe double stranded DNA damage, which is hard for the cancer cell to repair, and it dies.  Secondly, the physical entanglement which remains stops the clean separation of the chromosomes during mitosis.  Depending on the Topo II inhibitor in use, this can trigger a cell cycle checkpoint which stops the cell dividing Downes et al, 1994, or can cause the cell to rip the chromosomes to pieces as it tries to separate them anyway.  I worked in the same lab as Downes et al, above, and have done this experiment with several Topo II inhibitors, including etoposide and doxorubicin.  It's quite spectacular.


text:
Imidazoline receptor agonist in clonidine?
I am thinking which pathway is more important in hypertension, ADHD and withdrawal of clonidine:

alpha-2 agonist
imidazoline receptor agonist (maybe)

Alpha-2 is the classical one. Pubchem starts to have more more info about imidazoline receptors.
How does clonidine work in hypertension, ADHD and withdrawal?


text:
Is missing Q wave characteristic for Wolff-Parkinson-White Syndrome?
No my study books says about that no Q waves in WPW syndrome.
They are about wide QRS complex often however.
I heard today that the characteristic property of WPW is often a missing Q wave, like here

This is caused by the presence of an abnormal accessory electrical conduction pathway between the atria and the ventricles.
However, some books are about delta waves which is characteristic in the above picture.
However, it is many times very difficult to see.
These missing Q waves are however much easier when PRS complexes.
How much false positives do you get if you categorize all missing Q waves and PRS complexes as WPW syndrome?
How characteristic is the missing Q wave for WPW syndrome?

In Wolff-Parkinson-White syndrome, the normal Q wave is usually masked by the preexcitation action potential which produces the delta wave. Despite this, missing Q wave is not a diagnosis criteria of the syndrome, and up to 70 percent of the patients show a negative delta wave which causes differential diagnosis problems because it is confused with Q, according to Emergency Electrocardiography.

When the delta wave is negative, this simulates a Q-wave. This is known as a pseudo-infarction pattern, and is seen in up to 70% of patients with WPW.

And this negative delta wave also helps in determining action potential origin, according to Medscape.

A general rule is that Q waves (negative delta waves) point away from the earliest site of ventricular activation, which is typically the insertion point of the bypass tract.

No, you can't categorize PRS complexes as WPW syndrome. In fact there is no PRS complex. A classic ECG of WPW will show a shortened PR segment and a widened QRS (or RS or RSr' or however it looks) complex.


text:
What are the consequences of inbreeding?
Inbreeding increases the risk of getting two identical recessive genes, alleles, that cause a disease which wouldn't have been activated with mixed genes. That's how I understand it anyway. But I sometimes read and hear that inbreeding among humans also causes decreased intelligence, especially emotional and social intelligence. Is there any support for such claims, and if so how does that work?

There is indeed evidence that inbreeding in humans lowers intelligence of offspring.

In summary, our comprehensive assessment revealed that parental consanguinity and degree of inbreeding was significantly associated with depression in intellectual behaviors among children. Factors other than inbreeding showed little influence, suggesting that genetic component (i.e., inbreeding) was more influential over these parameters under study. Moreover, the depression in cognitive abilities seems to be more prominent due to increase in the degree of inbreeding (F).

Estimating the Inbreeding Depression on Cognitive Behavior: A Population Based Study of Child Cohort

A thorough literature search resulted in 95 studies. There were 15 studies that provided sufficient data for a meta-analysis. The studies were divided into four categories of inbreeding, showing values of an inbreeding coefficient (f) of .046, .063 (first cousin marriage), .125 (double first cousin marriage), and .25 (incest). The study’s hypothesis of a linear relationship was strongly confirmed. Over four categories, degree of inbreeding correlated highly with average IQ depression, r = .91. The current meta-analysis shows that the most common type of consanguinity, first cousin marriage (f = .063), may lead to a depression of about six IQ points, whereas incest (f = .25), the most severe type of consanguinity may cause a depression of about 28 IQ points.

Is there a linear relationship between inbreeding and mental ability?: A meta-analysis
Another study reaches a similar conclusion:

This result is interpreted in light of cultural feedback theory, whereby it is suggested that consanguinity could subtly influence IQ at larger scales as a result of small IQ handicaps bought about through inbreeding being amplified into much larger differences through their effect on factors that maximize IQ such as access to education and adequate nutrition.

About the mechanism behind the IQ decline caused by inbreeding:

The study of Morton (1978) study revealed that the offspring of
  first-cousins had over a five times higher risk of mental retardation when compared to controls. The study concluded that declines in IQ and the increase of mental retardation are consistent with rare recessive alleles associated
  with around 325 loci, whose likelihood of being transmitted into offspring increases with the relatedness of the parents.

Inbreeding depression and IQ in a study of 72 countries

Do you have any clue as to how such a complicated or subtle effect can be caused genetically, microbiologically?

If you want more information about the genetic effects behind iq depression caused by inbreeding read the answer by @AlexDeLarge below. He describes the mechanisms very well.

You are right. Inbreeding strongly increases overall homozygosity which subjects inbred individuals to diseases caused by rare recessive alleles. In non-inbred individuals the chance is quite low to receive those because many deleterious variants (and in fact, most segregating alleles we can observe) are recessive. Most often, but depending on the dominance coefficient, these 'hide' in healthy heterozygous carriers and when very closely related individuals breed (with a lot of variants that are identical by descent) there is a high chance that some of the 'hidden' deleterious variants are passed to the offspring.
You have to be aware that there are in fact two conceptually different processes that can be both be referred to as inbreeding but are also somewhat continuously linked (see below):

Mating systems that allow offspring between actually related individuals (measured by the degree of relatedness), what in humans often is referred to as incest or consanguinity.
Populations with very low effective population size $N_e$ generally exhibit higher relatedness due to lack of genetic diversity (excess of homozygous sites). Therefore, populations with low $N_e$ are referred to as inbred even if no actually related individuals are mating.

There is some evidence that inbreeding in the first sense is linked to cognitive abilities in humans:

Bashi (1977) investigated the effect of offspring having first-cousin (i.e. between children of siblings) and double first-cousin (i.e. between children of siblings and unrelated siblings, sharing as much variants as half-siblings but with more recombination events) parents while (at least somewhat) correcting for socioeconomic effects. He found an inbreeding depression with respect to cognition that could

result either from the general increase in homozygosity [...] or from decrease in performance resulting from homozygosity for specific recessive alleles (highlighted by me). The higher variance of the double cousin group in some of the tests favours the second interpretation.

Woodley (2012) presents evidence for slightly lower IQs caused by inbreeding, however, he also mentions that the effect is way smaller than socioeconomic effects:

Consanguinity could subtly influence IQ at larger scales as a result of small IQ handicaps bought about through inbreeding being amplified into much larger differences through their effect on factors that maximize IQ such as access to education and adequate nutrition.

Fareed and Afzal (2014) investigated verbal IQ, performance IQ, and full-scale IQ and found that all of these IQ parameters are significantly lower in inbred children compared to non-inbred children - actually the difference increases significantly with the degree of relatedness. They conclude that there is

evidence for inbreeding depression on cognitive abilities among children.

Please keep in mind that, for for sociological/ethical reasons, this is highly controversial, especially when the two concepts above are intermixed - human populations underwent differential and variably strong periods of low $N_e$, i.e. were subject to stronger or weaker inbreeding in the second sense. When reading the citation of Bashi (1977) above carefully, you will notice that he takes good care not to intermix those. Inbreeding in the first sense leaves large runs of homozygosity (ROH, blocks without heterozygous sites, i.e. a clustered and local lack of variation) whereas inbreeding in the second sense increases homozygosity in the genome less selectively. Therefore, the distribution of homozygous sites can be used to infer whether inbreeding is recent (first sense) or old (second sense) (see for example McQuillan et al. (2008) - here you see that both concepts form a continuum: where do you set the cutoff between recent and old? what is an appropriate threshold size for ROH? ...). Regardless, Bashi's findings indicate that effects of inbreeding are caused by recent inbreeding as he presents evidence that his results are rather driven by specific deleterious recessive variants than overall excess homozygosity. Finally, even though the study by Fareed and Afzal (2014) shows rather large effects of recent inbreeding in IQ measures, the results from Woodley (2012) show that one needs to be really careful to separate genetic from environmental components as his study suggests that the latter contribute more to the observed decrease in IQ.

Does the depression in cognitive abilities, or the effects of inbreeding in general, cease when having children with a non-related partner, or are there effects that last for generations after inbreeding stops?

@LocalFluff: That's not easy to answer. Usually, intelligence is pretty heritable but also strongly influenced by the environment. On the other hand, outbreeding is also very powerful, so I would expect (and this is based on intuition) that mean intelligence of individuals with recent inbreeding would increase rapidly in the subsequent generations but might still be sightly lower than average for some time, especially if socioeconomic factors (that tend to go along with consanguinity and could have a stronger impact on intelligence than the actual inbreeding) also have a negative effect.

Inbreeding, in nature at large, has one primary effect, as you said. It increases the chances of two copies of harmful, recessive alleles. Consequently, offspring are much more likely to suffer from genetic and/or degenerative diseases.
As for intelligence, some studies have indeed concluded that inbreeding can lead to a lower IQ (see this answer for the exact quotations), it is possible that there are other factors at play. For instance, those from a lower socio-economic background tend to be of lower intelligence, although as with everything there are exceptions. Whilst I have struggled to find a source for this, it is statistically more likely that those of a lower socio-economic background will exhibit poor mental health and/or partake in the act of inbreeding.
Consequently, due to the fact that intelligence is largely heriditary, the offspring of inbreeding will tend to be less intelligent. As a result, it is difficult to determine that there is a causal relationship between these correlating factors.

I would think that poverty and oppression are consequences of low intelligence rather than its cause. Instead of adjusting data for how poverty and oppression affects intelligence, one should maybe check how inbreeding causes poverty and oppression. An economy only consists of specialized humans interacting with each other, so social competence is the most important factor for wealth creation.

In addition to everything mentioned above, it should be noted that inbreeding leads to an increased chance at schizophrenia and bipolar disorder. According to one of the studies called Inbreeding and serious mental illness in the first Spanish Bourbons states that inbreeding leads to a point where a person "accumulates pathogenic alleles", which is what leads to an increase risk of suffering from these particular mental disorders.

"accumulating pathogenic alleles" seems like very loose wording (as explained by other answers, inbreeding doesn't inherently lead to higher mutation rate, fixation rate, or drift - it primarily exposes the phenotypic effect of existing deleterious recessive alleles) - can you provide the link to the study you're referring to?

(article is in Spanish so it's hard for me to follow it .. .Royuela-Rico, A. “[Inbreeding and serious mental illness in the first Spanish Bourbons].” Revista de neurologia 71, no. 2 (July 1, 2020): 61–68. https://doi.org/10.33588/rn.7102.2019508.
)

@BenBolker I can provide another study in English and I am not saying inbreeding inherently causes higher mutation rate in all patients, but the study seems to say that inbreeding may increase the chance of accumulating alleles that could lead to genetic changes in the subjects that raises the chance of developing schizophrenia and bipolar disorder: none of this is absolute, but it seems to boost the probability of something like this happening.

All I was suggesting was (1) it would be good to include the citation information in your answer (e.g. in the format I gave in my comment, and (2) that last statement seems a bit muddled to me (it may be muddled by the original authors, or it may be a translation problem/might make sense in context).  The rest of your answer seems fine to me.

My understanding, NOT based on any study, it purifies the gene 'pool' since mutation derived alleles variation will be lost thru' generations just like we don't have much of our grand grand's 'unique' allele.
This is bad as it happens in farms, when an decease that infects one, could eliminates all the populations, to be exact, barring a few left.
In the ever changing environment as in evolutions, singular gene pool will be hit with extinction even thought it might prosper if and only if the same good old 'environment' persists.  Environment here includes everything in the ecosystems.

Welcome. We ask answers to be backed up by credible sources, and preferably journal papers. Unsubstantiated claims face downvotes and deletion.

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


text:
Identify a small bug, possibly a plant bug?
We found this bug in a bedroom in southern California. It's small: the body is about 5mm and the length including legs and antenna could be up to about 10mm. It's mostly black, though the abdomen from the bottom appears to have gold highlights under light when I used a flashlight. In sunlight it appears somewhat brownish. It looks like it has wings which forms sort of an "X" pattern on its back. The legs are dark black or brown but may be somewhat translucent in sunlight to appear an orange-gold color.
What species is it? It looks to me a little like a plant bug (phylinae?) or roach or beetle but I'm not sure. And could this species bite?

I've seen this thing too. I don't know the species, but I do know it bites. Be careful!

This may be an assassin bug, Reduviidae. These may indeed bite.

This is a plant bug (family Miridae); going deeper isn't possible on the basis of a photograph, except for some common economic species (the key to genera in How To Know the True Bugs is almost 200 couplets long!).  Most species of the family are plant feeders (hence the common name); biting humans is unlikely.
Reasoning (from Comments):
The top right photo [from the OP's post] shows that the front wing has a cuneus (a section of the hardened part of the wing on the outer margin set off by a groove), which is characteristic of that family and the broad-sense "Anthocoridae" (which includes three smaller families); none of the photos show simple eyes (the eyes we see are compound), which eliminates "Anthocoridae" and the subfamily Isometopinae of Miridae; the remaining seven Nearctic subfamilies are still possible

Welcome to Biology.SE and thanks for your answer. It is difficult to assess whether your answer might be correct or not. I know it is very hard to ID insects to the species level and therefore I like your conservative approach, giving the family only. But could you please still provide evidence for your claim that this species belongs to Miridae, maybe by discussing some of its characteristics and compare them to the specimen on the original question? Thank you!

The top right photo here shows that the front wing has a cuneus (a section of the hardened part of the wing on the outer margin set off by a groove), which is characteristic of that family and the broad-sense "Anthocoridae" (which includes three smaller families); none of the photos show simple eyes (the eyes we see are compound), which eliminates "Anthocoridae" and the subfamily Isometopinae of Miridae; the remaining seven Nearctic subfamilies are still possible.


text:
What determines the sex of hybrid offspring?
I'm aware of the usual definition of Haldane's rule, which says that, if the offspring of inter-specific hybrid offspring are sterile, then the sterile offspring will be of the heterogametic sex. That is, for example, females in birds, and males in mammals. But I'm a bit confused. This implies that non-sterile hybrids are also produced, which rarely happens.
So, I have two questions, please:
 1. Does Haldane's Rule really mean that only offspring of the heterogametic sex are produced?
And 2. If so, please account for the exceptions. Crosses between Golden Pheasants and Lady Amherst's Pheasants regularly produce female as well as male offspring, as do crosses between Ring-necked Doves and Barbary Doves. Thanks!

XY and ZW are the heterogametes - males in mammals, females in birds

Yep sorry - wrote it the wrong way around

I am detecting a bit of confusion in you wording of Haldane's rule.
Haldane's rule makes predictions on the fertility of offspring from an inter-specific cross, not the sex-ratio of the offspring from the cross.
"if inter-specific hybrid offspring are sterile, then the sterile offspring will be of the heterogametic sex."
In inter-specific crosses there is not an effect on sex-ratio of the resulting offspring, but a effect on the ability of the F1 offspring to reproduce.
For the offspring, those of the heterogametic sex, males in mammals (XY) and females in birds (ZW) will be sterile while the homogametic offspring will not be affected by hybrid sterility.

Thanks. But that's what I don't quite understand:  virtually all mules, for example, are females. Virtually all canary mules are male. And virtually all hybrids are sterile, including the mules of both. It seems to be the opposite of Haldane's rule in both cases. Sorry for my late reply, by the way - I didn't realise I had answers.

With these mule examples, it is important to consider how distantly related horse and donkey are. Haldan's rule could be acting, but there are likely other effects on top of it causing a different result. Many 'miscommunications' could mess up development when the diverged horse and donkey genomes are mixed. Haldane's rule is illustrated more clearly with closely related sub-species or species because there are fewer incompatibilities which would affect development. The effects much stronger in the XY or ZW hybrid offspring.

Many thanks. It seems there are still a lot of unanswered questions relating to hybrids. Interesting stuff.

As already stated Haldane's rule doesn't always apply to odds of sex being born, it usually applies to the odds of that hybrid being fertile based off of whatever sex it actually was.  Haldane's rule can also apply to the odds of a sex being born at all, though this situation is run into less often.  So in short, no the vast vast majority of the answer to your first question is no, it doesn't mean that only one sex is produced.  The majority of the time when Halden's law applies it only affects fertility of the offspring not the production of them.
Let me get into more specifics though, to help clear things up better.  I think I detect two main conceptual mistakes which may be leading to your other confusion, so let me address them and see if it answers all your
confusion. At least one, maybe both, seem related to the way you quoted Haldane's law, so let me first quote a slightly more accurate version of the law, straight form wikipedia:

When in the F1 offspring of two different animal races one sex is absent, rare, or sterile, that sex is the heterozygous sex (heterogametic sex)

Halden's rule doesn't apply to all hybrids
The law starts by saying "when in f1 offspring one of 3 situations occur it will be the heterozygous sex.  I think the first confusion is simply an attempt to apply this rule a little too broadly instead of limiting it to these categories.  In your example of the Pheasant's it appears that both sexes of hybrids are fertile.  Since neither sex is rare or sterile Haldane's rule simply doesn't apply, the precondition isn't met so you can't say anything about they heterozygnous sex.
In the case of the doves, well I'm not an expert at this but as far as I can tell Barbary and ringneck are two names for the same dove so I'm not sure that is a hybrid at all.  I may just be misunderstanding dove nomenclature/classifications here, but in any case it looks like most doves hybrids are fertile so if I had to guess Haldane's rule doesn't apply in this case either.
However, just because your specific examples may not apply that doesn't necessarily invalidate the entire question.  It is certainly possible species where Halden's rule applies where children of both sexes are born, in fact this is usually the case.  Thus let's get to the other confusion.
Haldane's rule applies when one sex meets listed conditions
One confusion you seem to have is that the rule seems to imply that fertile hybrids exist despite the version of the rule you quoted specifically saying that halden's rule applies when hybrids are sterile.  That's because the actual rule applies only to one sex, meaning that one sex will be infertile and the other sex fertile.  If both sexes are infertile, as with the mule, Haldne's rule doesn't actually apply since it's not a trait unique to one sex(except when it does...I'll come back to that).
When precondition X applies the heterozygnous species demonstrates that condition
The law states that if offspring are "absent, rare, or sterile" that sex is the heterozygnous one. Those are three conditions any of which can apply, this doesn't mean all the conditions apply.  The most common examples of Halden's law your likely to run into is where one sex is sterile, in which case that sex is sterile, that doesn't mean it has to be sterile and rare and absent.  For that matter in cases where one sex is rare it's possible that the sex will be fertile on the odd example it's born despite being rare.
So back to what I said at first, most often Halden's law means two sexes that are equally common, but where one sex is sterile when it's born.  The best example that I can think of right now is with bovine hybrids, where cattle were often crossed with other bovines to get the 'best' bovine to raise for meat was common.  Crossing bison with Cattle produced more resiliant and better animals that were easier to raise, the only problem was that males were born infertile while females were fertile.  This resulted in an inability to keep hybrid breeding populations without males to mate and thus keeping a 'feral' breeding pool of bison cows to mate with cattle bulls; which was a problem since bison weren't domesticated and keeping breeding stock was an issue.  Thus a very common hybrid ran into issues due to Haldane's rule, keep this issue in mind, I'm coming back to this example later for my last point.
It is true that some hybrids have only one sex common due to Haldne's rule, I can't think of an example right now but there are many, just none exist in the common big/domesticated mammals I'm most aware of.  Usually if a sex is rare that sex is likely to also be infertile, the issues that cause the sex to be rare will usually also make it infertile.  However, as I understand the genetics it's entirely possible for a species to have one sex be rare, but that sex be fertile when it is produced; in fact id love an example if anyone can suggest one!
Laws are really just rule's of thumb
You don't want to apply this, or really any genetics law, too exactly or biology is going to decide to throw you a curve ball.  Because of the oddities of the ways genes are combined, and even the possibility of random mutation, many 'impossible' situations still come up.  Look at mules, thought to be infertile and yet a half dozen fertile mules have been documented at least, in fact most common 'sterile' hybrids I know of have examples of fertile hybrids being produced.
Which brings us back to the beefalo example above.  Remember keeping bison cows for breeding stock was a major problem for them?  Well that problem solved itself when a fertile male beefalo was born.  Even though they are almost always infertile this male was fertile, as were both sexes of his offspring.  This was due to random chance (I don't know if it was mutation or just the combination of the genes specifically), but a rule was broken by genetics.  Thanks to this we were able to start up hybrid breeding populations of beefalo, all decedents of this male, beefalo are the most common bovines raised for meet now of days!
The point being go in expecting any rules to be bent in genetics at time.  There are exceptions to most of these rules, life finds a way yadda yadda.
Hope all that rambling gave you a better idea of how the rule applies.

Many thanks for taking so much time to answer this. Apologies for not replying sooner - I have only just found the answers via Twitter, which I rarely use

Apologies also for confusion over Ring-necked Dove - I'd intended to write [Eurasian] Collared Dove but was distracted. Husband has bred some of these and they do appear to be sterile and occur in both sexes. Certainly canary hybrids with finches are virtually all sterile, and virtually all males. I had recalled reading an explanation of this in Tim Birkhead's book The Red Canary which, (as far as I remember) attributed this sex bias to Haldane's Law - hence my confusion. Many thanks, once again.

Thanks very much also for the information about beefalo - that was all very new to me and useful information.


text:
What happens if we continuously stimulate a mimosa plant?
I know there is some mechanism in humans by which we start to ignore a certain stimuli if it persists for a long time (e.g., we don't feel our shoes all the time !).
Can the same thing happen in Mimosa pudica? Can it again get it's original arrangement of leaves if it is stimulated without interruption?
I think it should do this, otherwise it will not be able to grow if it is surrounded by bushes from all the sides as it will be stimulated constantly and so will be unable to photosynthesize properly.

This has actually been experimentally shown by multiple scientists, who all came to the conclusion that Mimosa plants, when constantly stimulated, eventually become insensitive to these stimuli.
This page of the Google Books preview of the book Invertebrate Learning presents a number of primary sources on Mimosa and other plants which react to tactile stimulation. While most of these primary sources could not be immediately found by a Google search, I was able to find the original book by Bose (1906) which describes habituation in the Mimosa plant. (Chapter IX, Page 109)

It will be found,
  however, that if a Mimosa leaf
  be continuously stimulated
  by successive blows or taps,
  in the manner of Pfeffer's Normal Response
  experiment, the leaf Will at
  first fall. But, though the
  blows be continued, the
  petiole will, after a time,
  return to its normal erect position. In this erect posture,
  however, further blows prove to have no effect upon
  it, the leaf being now insensitive.

100 years have passed and we have not yet studied the actual molecular mechanism behind this. Apparently, nobody cares about a small damn plant!!

@WYSIWYG Funding ! Funding ! Funding !

Mimosa leaves have mechanoreceptor cells which sense the mechanical stress through proteins called mechanoreceptors (they are similar to the ones responsible for sense of touch in animals). When stimulated the mechanoreceptors cause ion channels to open leading to depolarization. This generates an action potential (AP; like neurons) which in turn activates the motor cell (Visnovitz et al., 2007). Motor cells cause leaf movements by change in their interior turgor pressure (similar to opening and closing of stomata).
Repolarization (like in neuronal AP) takes time and Mimosa would not respond to stimuli that are too frequent. The time required for the turgor pressure to relax would be an additional factor.
I am no plant biologist but if I compare this situation with that in neurons, I can speculate that long term non-responsiveness similar to LTD may happen because of down-regulation of mechanoreceptors. It has actually been shown that Mimosa does actually become insensitive to a persistent stimulus such as a continual water drop and moreover exhibits a long-term "memory" of this non-responsiveness (Gagliano et al., 2014). However, the exact molecular mechanism has not been elucidated. Again, there would be thresholds (on amplitude and frequency) for the signal to elicit these kind of changes.

References

Visnovitz T, Világi I, Varró P, Kristóf Z. Mechanoreceptor Cells on the Tertiary Pulvini of Mimosa pudica L. Plant Signaling & Behavior. 2007;2(6):462-466.
Gagliano, Monica, et al. "Experience teaches plants to learn faster and forget slower in environments where it matters." Oecologia 175.1 (2014): 63-72.


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How do you differentiate between SR protein and SR-like protein?
What are the criteria that the researchers use to choose whether a protein is an SR protein or and SR-like protein?

Im not 100% certain. If something is called an x-like protein, it usually means it is homologous and has some sequence and / or structural similarity to x. However, there may not be enough biochemical evidence to say definitively that it is in family x. I came across this paper where they are speaking about an SR-like protein. They said:

While budding yeast lack alternative splicing, they do have three SR-like proteins: Npl3, Gbp2, and Hrb1. However, these have been best characterized for their roles in mRNA export, leaving their potential roles in splicing largely unexplored.

So in this case the protein has a serine/arginine binding domain and an RNA binding domain (just like SR proteins) but most of the biochemistry points to them being involved RNA export, not splicing (splicing, of course is what SR proteins are known for). So, they get the name SR-like. It will vary though. There is not a unified protein naming system


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What are the functions of disulphide bonds?
What are the functions of disulphide bonds between amino acids in proteins or peptides?

Disulfide bonds form between different amino acids of a protein chain and the help to stabilize and maintain a distinct three dimensional form. In principle this looks like this (pipcture from the Wikipedia page on Disulfide bonds):

Disulphide bonds (or bridges) can also hold different subunits of larger protein complexes together, one example for this would be antibodies. Here the light and the heavy chains are connected by disulfide bonds, they also play a role for maintaining the structure of the single protein chains (image from here):

Disulphide bonds occur in proteins, not amino acids, although they involve a covalent bond between two amino acids (both cysteine).
The received wisdom is that disulphides are used as extra stabilisation of the structure of proteins which are secreted, or which have an extracellular domain. It's important to get hold of the idea that they do not occur in the cytoplasm, but are only formed in proteins which pass through the secretory pathway: they are formed in the endoplasmic reticulum (ER), and there are resident ER proteins (protein disulphide isomerases) whose function is to assist in their formation.
Classical examples of disulphide-bonded proteins are insulin (where the A and B chains are linked by disulphides) and immunoglobulin G where each Ig domain has an intradomain disulphide, and where the heavy chains are linked by disulphides. There are, of course, many others.
Cells also contain the tripeptide glutathione which includes a cysteine residue. the ratio of oxidised (disulphide bonded dimers) to reduced (monomers) glutathione helps to set the redox state of the cytoplasm and the lumen of the endoplasmic reticulum.


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How do tight junctions in stratified squamous epithelia affect nutrient supply?
In histology we know that epithelium tissue isn't vascularized so it takes the nutrition from Lamina propia (CT) via diffusion and in other hand we know all epithilial cells have tight junction which inhibits the flow of substance so how can it diffuse nutrients between themselves because of the tight junction how can they distribute nutrients, same way in capillaries which are endothelium  how interstitial fluid passes throw endothelial cells because of thier tight junction?

Most epithelial cell layers a thin so that is not a problem. The epithelial layer of the skin gets less nutrients the further their distance to the basal layer is and eventually these cells die and form the horny layer of out skin.

Tight junctions function to occlude the baso-apical flow of small molecules. However, tight junctions do not always completely seal a cell's lateral surface. In addition to regulating diffusion, tight junctions promote cell polarity. Establishment of polarity and prevention of water loss are the major roles of tight junctions in stratified squamous epithelia.
In simple epithelia, transcytosis allows the flow of molecules through a cell with tight junctions. However, stratified squamous cells do not use transcytosis for nutrient supply.
In the stratum granulosum, skin cells lose their nuclei and become non-viable. In the stratum lucidum, an oily layer is produced by exocytosis.
It is the loss of nuclei, organells, production of an oily layer at the stratum granulosum and lucidum that contributes most to the death of skin cells, not the limits of nutrient diffusion.


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Does chromosomal crossover result in a mutation?
Is chromosomal crossover considered a mutation? Would this be a large-scale mutation?

There are many different ways a DNA sequence can change. Labeling a change as a mutation implies that there was a biological process in which DNA was damaged then not properly repaired.

Crossing over during the formation of gametes does not result in a mutation.
Crossing over during repair of a double stranded DNA break does result in a mutation.

Yes. And it is especially considered a large-scale mutation when compared to point mutations which effect single bases.

I disagree with this answer. Have a look at the Wikipedia pages for mutation and recombination. Crossing-over may create new combinations of existing alleles/SNPs but it does not create any new ones. Even if there is a piece of sophistry which can be devised to defend this answer it is neither helpful nor useful to lump these two together as one.

The scale of a mutation is not simply a matter of counting bases. A frame shift mutation from a nucleotide deletion completely changes a translated protein. However, a change in any number of bases in a gene would only affect those bases, not the entire gene. The 'scale' of a mutation is situationally dependent.


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How does vasomotor and bronchomotor reactions equilibrate local blood flow to correspond local ventilation?
I am trying to find some figure(s) to explain this.
There is probably better name for "bronchomotor" reaction.
They seem to opposite terms and actually affecting same things (alveolar diameter/tone); one increasing, while the other decreasing.
I am been reading Pocock and Guyton but I am not happy in any any figures.
Which figures can you use to answers this question?

Maybe this is due to my limited anatomical background, but I don't really understand your question. And how should we find better figures when we don't know the ones you have?

I have not found any good picture. Probably, you cannot show this in one picture which I am trying to do. I will post some separate pictures about these two processes tomorrow evening.


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Transcribing DNA to mRNA with introns
I have a problem in my bioinformatics class that I thought I was doing right, but someone else is getting a different answer. Here is the problem:

Given the following DNA sequence, 5'-GGATCGTGCCACCATCCACCATCGTTA-3', if two introns are in bases 3-9 and 15-22, what is the mRNA transcribed? Give the answer 5' to 3'. Note that the first base is base 1.

And here are the steps that I took:

5'-GG ATCGTGC CACCA TCCACCAT CGTTA-3' (remove the bolded)
5'-GGCACCACGTTA-3' (new string)
take reverse complement
swap T's with U's

Is this correct? Or where am I going wrong?

If you look on ensembl.org, which real biologists use, the DNA sequence given for a gene, and the DNA sequence given for a transcript are the same, if the gene runs in the forward direction.  They aren't rev-comped; people don't even substitute U's in the sequences.  So just keep in mind that some of what you are doing is just to prove that you really know that RNA has U's, that there is a difference between template and coding strands...real biologists take that for granted

I think the only place you are going wrong is in getting confused about strands ("take reverse complement").
5'-GGATCGTGCCACCATCCACCATCGTTA-3'   << coding strand
3'-CCTAGCACGGTGGTAGGTGGTAGCAAT-5'   << template strand

The coding strand has the same sequence as the transcribed RNA (apart from T>U), so the primary transcript is:
5'-GGAUCGUGCCACCAUCCACCAUCGUUA

Then, positions of introns:
5'-GG AUCGUGC CACCA UCCACCAU CGUUA

and after splicing:
5'-GGCACCACGUUA

Do you take the reverse complement after the splicing? It looks like we got the same result, I just took the reverse complement and flipped the T's to U's last

You don't need to take the reverse complement - the 'top' strand of the DNA (i.e. the sequence in your question) is the same sequence as the RNA, because the RNA is made using the complementary strand as template. I included the 'bottom' strand for clarity.


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Ribosomal RNA amount in a Drosophila cell
I am isolation RNA from Drosophila larvae brain with TRIzol method. What percentage of extracted RNA will be ribosomal RNA? I am only interested in mRNA, so I am trying to figure out whether I need to get rid of rRNA. Thanks

Percentage of what? Total cell mass/volume? Of total RNA moieties? Of total nucleic acids?

Ratio of ribosomal RNA in total RNA if I rephrase it.

OK, please [edit] your question to something like "I am extracting RNA using methodX, what percentage of extracted RNA will be ribosomal?" The percentages will also depend on the method used to extract the RNA.

The protocol you are using will not only leave the sample with rRNA but also non coding RNA.
Many RNA protocols will separate mRNA by affinity of a carrier to the polyA tail.  This protocol references an older paper that estimates that only 5% of RNA is mRNA.  I'd be surprised if this ratio changed by more than 2-3 fold in drosophila.
I assume that %age is by weight but it could be a densitometry measurement which is similarly interpreted.

Thanks! As a subsequent question: Do you think that huge amount of rRNA will affect my downstream experiments such as RT-qPCR? I am only interested in mRNAs.

I've not done qPCR.  I would not hesitate to compare multiple standard protocols to get a better sample. Looking at a couple of qPCR protocols you're right I only see Triazol preparations used.  PCR is pretty efficient as long as the primers are specific.  Some more homework before doing the experiment won't hurt you :)


text:
How do you find pre-miRNAs from mature miRNA Blast output?
So in short, I did a blastn with standalone blast using all known miRNAs against the EST sequences in a genome (word length 7 and e-value 0.01). Now to confirm one of the next steps would be obtain the pre-miRNA sequence of each hit and do an mFOLD for structural confirmation. Each paper I read always mentions to get a sliding window (of 70 - 100 nt length) but how do you get this sliding window from the BLASTN output.. Do you have to code something yourself or is there an easier way to do it. Thanks.

miRNAs in EST- I am a little skeptical on this..

sorry for the late answer.. I am not sure if you still need it now.

DISCLAIMER: I have never worked with miRNAs.
However, from what little I know, the mature miRNA is produced by modifying the pre-miRNA. This means that you should be able to infer the pre-miRNA by mapping your miRNA to the genome using a tool like BLAT. Since you already have an EST which represents a transcribed sequence, you can map your EST back to the genome. You can simplify this by using a tool like exonerate that also models splicing.

A BLASTN would work for mapping the mature miRNA but you should correct some parameters.
E-value is fine but increase the word length. Keep it close to 17 because you are interested in perfect matches. With miRNA small mismatches can mean a different miRNA altogether. Also run for only plus/plus alignments. (You can see this post on biostar for details on how to do it)
What you can also do is to use bowtie (sometimes BLAST is very slow and though BLAST allows multiple threads there is no option for utilize multiple cores i.e true parallelization). Again use the option --norc to avoid plus-minus alignments.
Use bowtie-build on your EST sequences to make an index.
However, there is one more problem; it is unlikely that you'll get pre-miRNA sequences in your EST collection. This is because the stable form is mature miRNA and pre is generally too shortlived to be sequenced properly without appropriate selective measures.
Capturing small RNAs by sequencing is also not that straightforward. It needs size fractionation of RNA and subsequent library preparation from the small RNA fraction. So I guess you will not discover miRNAs from ESTs.
If you have small RNA sequences then you can align it to the genome and then select the $\pm 70$ nt to find the hairpin.
In fact there is an algorithm called mirdeep which does that; you can use it and avoid writing your own codes. If you are good at perl then you can modify it to suit your specific needs if any.

never used bowtie.. I am trying to work on blastn with the number of mismatches set to 2 at the moment. What would you suggest is a good clustering program to remove duplicate sequences

fastx_collapser will collapse redundant sequences. BLAST can get very slow for these things. It is better to use a short read aligner like bowtie.

thx.. will have to try bowtie maybe next time. Too far with the current project to retrack.


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Linkage disequilibrium with multiple alleles and loci
Linkage disequilibrium $\left(D\right)$ for two bi-allelic loci is defined as:
$$D=X_{11}X_{22} - X_{12}X_{21}$$
where $X_{11},\ X_{12},\ X_{21},\ X_{22}$ are the frequencies of the haplotypes $A_1B_1$, $A_1B_2$, $A_2B_1$, $A_2B_2$ respectively (the subscript number correspond to the two different alleles and $A$ and $B$ correspond to the two different loci)
My questions are

How is $D$ defined for more loci and a greater number of alleles?
How is $D$ defined when the number of alleles differ from locus to locus?

Let me know if my answer is making sense to you

LD describes the associations among alleles at different loci. For anything more than two bi-allelic loci, you need more than just one number to fully describe the associations. For instance, if we have three bi-allelic loci 1-3, we need the three pairwise LD coefficients, plus one extra three-way coefficient. In general, if we have $K$ loci, and the $k^\text{th}$ locus has $n_k$ alleles, there are $\prod_k n_k$ possible haplotypes, so to fully describe the state of the population we need $\prod_k n_k-1$ haplotype frequencies. If we instead want to use allele frequencies and associations, we'll therefore need $$\prod_k n_k-1-\sum_k(n_k-1)=\prod_k n_k-\sum_k n_k+k-1$$ LD coefficients. (Note that each locus is described by $n_k-1$ allele frequencies.) This means that things get complicated pretty quickly with many loci! If you want to dive into the details, check out Barton and Turelli (1991) and Kirkpatrick, Johnson, and Barton (2002).

Being a typical molecular biologist, I am a little uncomfortable with classical genetics terms. I might redefine some symbols (perhaps to mean the same) [It is like talking to oneself while thinking].

There are four DNA-blocks : A1, B1, A2 and B2. Ak and Bk are adjacent blocks. [Perhaps this is same as what you defined the symbols as]. A and B are contiguous DNA regions whereas 1 and 2 are different chromosomes (homologous regions). See the figure below.

The formula:
D=X11X22 - X12X21
basically means that the difference between the probability that the loci are in configuration I (11 & 22) or configuration II (swapped) (12 & 21). Lets say there is a third region (3) which is homologous to the two alleles which has DNA-blocks A3 and B3.
As LD is defined it is a difference in probabilities. Depending on how you define, it will take a negative or a positive value. When you have 3 recombinationally feasible alleles then there can be six cases:

C1: [A1B1] [A2B2] [A3B3]
C2: [A1B1] [A2B3] [A3B2]
C3: [A1B3] [A2B2] [A3B1]
C4: [A1B2] [A2B1] [A3B3]
C5: [A1B2] [A2B3] [A3B1]
C6: [A1B3] [A2B1] [A3B2]

In this case there is no single measure for difference. You can also do something like this:
LD1' = P(C1) + P(C2) - (P(C3) + P(C4) + P(C5) + P(C6))
Where LD1' is LD of region 1 and P(Cm) is the frequency of mth configuration.
Now, if there are 3 or more adjacent DNA blocks, you can only define LD, pairwise. It however, makes sense because linkage reduces with distance and you can calculate LDAC = LDAB x LDBC (A,B and C are contiguous in alphabetical order. If A and B are not linked then A and C cannot be linked.)


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Is sequencing error a function of the nucleotide being read?
Checking out on Google Scholar, I can see that for Illumina (just to consider one example) the sequencing error rate is of the order of 0.001-0.01 per nucleotide.
Talking about sequencing error, let's consider mismatches (substitution of one nucleotide by another) only. Knowing the "true" nucleotide at a given position, is it as likely to be read as any other specific nucleotide during a mismatch or are there bias? For example, if the true nucleotide is A, is it more likely to be found being as a G (as they both are purines) than a T or a C? Are some nucleotides more likely to be misread than others?
I am hoping the answer won't depend too much on the sequencing techniques.

Actually sailorgyaru's answer is very close. The base-calling in Illumina as is different from that of Sanger sequencing. In the latter a noisy position can be assigned to different nucleotides with different probabilities. In Illumina the bad quality can be because of multiple reasons- improper washing , bad signal capture etc. Poor washing may cause overall bad quality everywhere. Perhaps you may look at the mismatch frequencies of nucleotides in reads with overall good quality (mean phred >20). I suspect the mismatch is likely to be random.

Unfortunately, it does depend on sequencing techniques.
For example, in Illumina sequencing, each sequence fragment is amplified (in order to get a stronger signal) and forms a cluster on the microarray. Each cluster is sequenced by cycles of:

Adding fluorescent terminator nucleotides. These nucleotides are modified to contain an inhibiting/terminating group and prevents more nucleotides from being added. Theoretically, only one nucleotide is incorporated into every DNA fragment in this step.
Washing off excess nucleotides.
Capturing the incorporated nucleotide using imaging techniques and determining which base was incorporated (based on the colour of fluorescence).
Cleaving the terminator from the added nucleotides, so that the reaction can continue.

Image from Metzker, 2010.
This way, each fragment is synthesized, one nucleotide at a time, and each nucleotide that is incorporated gets detected. However, the first step is not flawless: sometimes more than one nucleotide gets incorporated into a certain DNA fragment, or no nucleotides get incorporated. Eventually, the DNA fragments in a cluster (all containing the same sequence) will fall out of sync ("phasing") and the fluorescent signal will become less clear, with a mixture of different colours. This is the main cause of sequencing error for Illumina machines, and also the reason why Illumina reads are relatively short (~300bp).
So to answer your question, in this example, nucleotides may be erroneously read as nearby nucleotides in that sequence. Errors will vary using other sequencing methods and how those methods work.
The article I linked earlier explains various sequencing methods in more detail. (Unfortunately, it's behind a paywall so some may not be able to view it.)

Welcome to Biology.SE and thank you for your answer. So just to make sure, you that indeed the probability for a A to be read as a given nucleotide is dependent of the nucleotide and dependent on the technic used? You're not only saying that the error rate is dependent on the technic, right?

I can't say for sure but I don't think it's dependent on the nucleotide (at least not the chemical properties of the nucleotide). Most sequencing methods use different coloured fluorescent markers to detect which nucleotide is incorporated, and which base is called depends on the intensity of the colour signal. Perhaps certain bases are more likely to be erroneously incorporated into DNA in general, but I've never seen that mentioned as a significant factor.

In the future, we recommend linking to cited works via PubMed or DOI. Publisher's websites can (and do) change. Additionally, please double-check your links before posting. The link to the Metzker paper was broken.

@MattDMo Sorry about that; thanks for fixing it!