transposable elements ( tes ) , mobile segments of genetic material , were first discovered by mcclintock . since then , they have been identified in a variety of eukaryotes . recent genome sequencing projects have consistently shown that tes make up ~50% of primate genomes , while coding dna occupies only ~2% of the genomes [ 3 - 5 ] . 1 ) , based on their manner of mobilization . dna transposons move using a cut - and - paste mechanism . in contrast , retrotransposons move in a copy - and - paste fashion by duplicating the element into a new genomic location via an rna intermediate . retrotranspons include short interspersed element ( sine ) , long interspersed element ( line ) , and human endogenous retrovirus ( herv ) . alu and short interspersed element / variable number of tandem repeats / alu ( sva ) elements are primate - specific retrotransposons , and their full - length is 300 bp and 2 kb , respectively . the alu element is the most successful sine in terms of its copy number ; ~1.2 million alu copies exist in the human genome . line is ~6 kb in length , and thus , it is much longer than the sines . this element has two open reading frames encoding enzymatic machineries essential for the propagation of the three elements ; the alu element depends on reverse transcriptase of line for making their dispersed copies in the host genome . in contrast to sine and line , which do not have long terminal repeats ( ltrs ) , the full - length herv ( ~10 kb ) has two ltrs , and three genes - gag , pol , and env - are located between them [ 8 , 9 ] . studies on active tes have suggested that the elements could alter gene expression by providing cis - regulatory elements , such as promoters , enhancers , and transcription factor binding sites . through these mechanisms , altered transcriptional activity could lead to dysfunctional and abnormal proteins . through de novo te insertion within a gene , tes could alter a gene product , which could be either harmful or beneficial to its host genome [ 11 , 12 ] . in cases where an inserted te causes a harmful effect on its host genome , the te is likely to go to inactivation and fossilization by evolutionary accumulation of mutations and silencing effects . since the divergence of the human and chimpanzee , ~6 million years ago are the alu , l1 , sva , and herv - k ( hml-2 ) elements . during the past 6 million years , 5,530 alu , 1,835 l1 , 864 sva , and 113 herv - k ( hml-2 ) elements are estimated to have been newly inserted in the human genome ( table 1 ) [ 8 , 14 , 15 ] . these elements could act as an agent causing human - specific genomic rearrangements via de novo te insertions , te insertion - mediated deletions , and homologous recombination events [ 12 , 16 - 19 ] . furthermore , some of the recent integrated tes are capable of producing new copies in the human genome . these de novo te insertions have the potential to cause a genomic difference among human populations and even human individuals , which could be related to human phenotypes and diseases . in this review , we describe species - specific tes and discuss how they affect their host genomes , focusing on illustrating the mechanisms that they utilize with examples . taken together , we suggest that tes , often called ' junk ' dna , in fact have many functions and play a significant and dynamic role in primate genomic evolution . comparative genomics allows us to investigate species - specific tes . through a combinational method of computational data mining and experimental verification , species - specific tes have been well studied in various primate genomes , including human , chimpanzee , and rhesus macaque . during the past 6 million years the majority of the identified elements belong to alu , l1 , and sva retrotransposons . these elements have contributed to the genomic difference between human and non - human primates through insertion and post - insertion recombination between the elements [ 8 , 22 ] . a master gene model has been generally accepted to explain the amplification of alu elements . in the model , only limited numbers of hyperactive " source " or " master " genes are able to produce a high number of alu copies over evolutionary time . one of the previous studies about the aluyb subfamily , one of the most active alu subfamilies in the human genome , found that the copy number of aluyb elements is very different between human and non - human primates ; a high copy number of aluyb elements exists in the human , but a very small number of the elements exists in non - human primates . the oldest aluyb element resides at its orthologous position in all hominid primate genomes , demonstrating that the aluyb subfamily emerged 18 to 25 million years ago . then , after approximately 20 million years of retrotranspositional quiescence , a major expansion of the subfamily occurred only in the human genome within the past several million years . to explain their successful proliferation in the human genome , a new model , " stealth driver , " was introduced . in this model , a high copy of the alu elements could be driven at least in part by " stealth driver " elements , which maintain low retrotransposition activity over extended periods of time . although this element has low retrotransposition activity , they have the potential to produce short - lived hyperactive copies responsible for the remarkable expansion of aluyb elements within the human genome . the copy number of alu elements is much higher than that of l1 ( alu , ~1.2 million copies ; l1 , ~520,000 copies ) . nonetheless , alu elements are responsible for ~11% of the human genome , because the alu element is much shorter than l1 ( alu average length , 300 bp ; full - length of line , 6 kb ) . through characterization of sequence diversity of chimpanzee - specific l1 subfamilies as compared to their human - specific counterparts , it was concluded that l1s experienced different evolutionary fates between humans and chimpanzees within the past ~6 million years . although the species - specific l1 copy numbers were on the same order in the two species ( 1,800 human - specific l1s vs. 1,200 chimpanzee - specific l1s ) , the number of retrotransposition - competent elements was much higher in the human genome than in the chimpanzee genome . all human l1 subfamilies belonged to a single lineage , but two distinct l1 lineages were identified in the chimpanzee genome . fewer than 1,000 copy numbers were detected in orangutan ( ~15 million years ago ) , and no sva detected in old world monkeys indicating sva is a hominid - specific element . like alu elements , sva elements retrotranspose to another locus in trans by using reverse - transcriptase encoded by l1s . due to the limited mobilization and short evolutionary time , the copy number of sva is very small compared to alu and l1 elements [ 15 , 26 , 27 ] . the older , sva_a to sva_d , evolved in a single lineage , whereas human - specific sva_e and sva_f were derived independently from their ancestral sequences . the copy number of sva was estimated throughout the primate genomes of human , chimpanzee , and gorilla , and there was no significant difference among them . the two elements , alu and l1 , showed a huge expansion at a specific evolutionary time along the primate lineage , but sva still did not show any burst in its copy number [ 26 , 27 ] . the comparison of human and chimpanzee genomic sequences showed that the two genomes have a much higher sequence identity than we expected [ 3 , 4 ] . in spite of the sequence similarity many studies have suggested that a number of tes are still active to retrotranspose and have the potential to cause genomic variations as a major driver [ 12 , 16 - 19 , 28 ] . in reality , tes have rearranged human and non - human primate genomes through various mechanisms , such as de novo te insertion , te insertion - mediated deletion , and homologous recombination between them ( fig . these genomic changes caused by tes have increased the genomic difference between human and non - human primates , and some of the human - specific genomic rearrangements caused human diseases [ 28 , 34 ] . advanced sequencing technology , including next - generation sequencing , and combined computational analyses have accelerated the studies on the dynamics of te mobilization . in reality , human - specific tes have been continuously investigated , and the majority of them are alu , l1 , and sva elements [ 8 , 14 ] . since the divergence of the human and chimpanzee lineages , the human brain has rapidly changed in terms of mass . it is not an exaggeration to say that alu elements are in part responsible for the human brain mass . interestingly , de novo 
 alu insertions have been identified in many human brain genes that are related to neuronal functions and neurological disorders . the inserted alu elements belong to aluya5 , aluyb8 , and aluyc1 , which are human - specific alu subfamilies . they belonged to two different subfamilies , pre - ta and ta ; ta is subdivided into ta-0 and ta-1 by diagnostic nucleotides . among hominid - specific sva subfamilies , sva_e and sva_f are only detected in the human genome , but the other four subfamilies , sva_a , sva_b , sva_c , and sva_d , are shared in human and other apes , including chimpanzee and gorilla . full - length hervs are ~10 kb in length , but most of the hervs existing in the human are defective due to truncation and accumulation of mutations during primate evolution . among various herv subfamilies , herv - k ( hml2 ) is the youngest element in the human genome [ 8 , 40 ] ; 113 human - specific herv - ks were identified in the human genome , and among them , there were 15 and 98 full - length herv - ks and solitary ltrs , respectively . these de novo te insertions showed polymorphisms among human populations and even human individuals [ 31 , 39 , 41 , 42 ] . therefore , they have the potential to be used as a genetic marker for racial identification [ 31 , 41 , 42 ] . actually , some of them somewhat decreased their host genomes involving the insertion - mediated deletion of host genome sequences [ 32 , 33 ] . through comparative genomic analyses , 50 l1 insertion - mediated deletion events were found in the human and chimpanzee genomes . the sizes of the deleted sequences were variable , and in sum , ~18 kb and ~15 kb of sequences were removed from the human and chimpanzee genomes , respectively . based on the result , it was estimated that l1 insertions may have deleted up to 7.5 mb of target genomic sequences during the primate radiation . alu insertions were also involved in the genomic deletions at its insertion target regions through alu retrotransposition - mediated deletion . a total of 33 deletion events responsible for a ~9,000-bp deletion in human and chimpanzee genomes were identified . it was suggested that alu retrotransposition may have contributed to over 3,000 deletion events , leading to a ~900-kb deletion during primate evolution . additionally , 13 sva insertion - mediated deletions ( simds ) were also identified in the human genome , and they deleted 30,785 bp of the human genome compared with the chimpanzee genome ( table 1 ) . among the 13 simds , 9 were associated with the sva_d subfamily , occupying the largest portion of svas , which suggests that simd frequency is directly correlated to the copy number of sva elements . furthermore , one of the deletion events occurred in the tmdc ii gene associated with sperm - egg binding prior to fertilization [ 43 , 44 ] . after te insertions into the host genome , they could generate genomic variations through unequal homologous recombination events between them [ 17 , 19 , 43 ] . the copy number of tes is closely related to the frequency of the recombination between them . thus , compared to other tes , alu and l1 elements have a high probability of generating genomic structural variations due to their ubiquity . in reality , 492 alu recombination - mediated deletions ( armds ) were identified in the human genome , and they deleted ~400 kb of human genomic sequences ( table 1 ) . about 60% of the deletion events were related to known or predicted genes , including three that deleted functional exons . thus , the armd process has produced a considerable portion of the genomic and phenotypic variations between humans and chimpanzees since the divergence of the two species . seventy - three l1 recombination - associated deletions ( l1rads ) were identified in the human genome . the sizes of the deletion events range from 56 to 64,113 bp , and ~450 kb of human genomic sequence was deleted through this l1rad process ( table 1 ) . thus , the l1rad event has deleted 25 times as much human genomic sequence as the l1 insertion - mediated deletion event [ 18 , 45 ] . the tes inserted in intra- and inter - genic regions could alter cellular gene expression , increasing genomic instability . about a decade ago however , genome - wide analyses of gene regulation by tes were recently conducted due to the developed high - throughput technologies . the findings showed that tes have many regulatory sequences , such as promoters , enhancers , polyadenylation signals , and cryptic splicing donor ( 5 ' ) and acceptor ( 3 ' ) sites , by which the transcript architecture of nearby genes can be altered [ 10 , 46 , 47 ] . when tes insert into the intronic region of genes , they could create a new exon by offering splicing sites , and this process is called " exonization " . this mechanism is related to exon variations , such as cassette exons and intron retention in exons , increasing mrna instability . the tes residing upstream of any gene could act as an alternative promoter , leading to new alternative transcripts with a new transcriptional start site . for example , ltr and l1 have sense promoters initiating their transcription and antisense promoters having the potential to initiate the transcription of other genes in the opposite direction [ 50 , 51 ] . there is a microrna gene cluster in human chromosome 19 ( c19mc ) , over 100 kb in length . this cluster consists of the duplication of a core cassette , including a minus - strand alu element . the cluster grew successfully during primate evolution , and the alu element promotes microrna expression by rna polymerase iii . tes not only initiate transcription but also terminate it by offering a polyadenylation signal . a full - length l1 contains 19 polyadenylation signals that could cause premature mrna truncation . the genes that contain tes in their genic region have a tendency to produce various transcript forms , causing transcriptome diversity . the orientation of tes could be a factor affecting gene expression , which is well described by a " head - on collision " hypothesis . during dna replication , dna polymerase collides with rna polymerase transcription complexes moving in the opposite direction to the movement of the dna polymerase . it was observed that the collision slows down the dna replication . in cases where active te exists in the opposite direction to its nearby genes , an rna polymerase transcription complex transcribing the te could encounter any of the rna polymerase transcription complexes transcribing nearby genes , which could reduce the expression of the gene [ 54 , 55 ] . in reality , transcription of the e - globin gene is repressed by an alu element that has been inserted in the opposite direction to the gene . on the other hand , tes inserting in the same direction to its nearby genes show no effect on the expression of the genes . histone modification plays an important role in gene transcriptional regulation , and through this process , the host genome could regulate the activation of tes [ 57 , 58 ] . in reality , most tes are accompanied by repressive histone modifications ( e.g. , h3k9me2 and h3k27me3 ) , which cause the formation of heterochromatin . conversely , tes could affect the expression of host genes through histone modifications [ 59 , 60 ] . the level of histone modifications was calculated in all families of human tes , and older te families carried more histone modifications than younger families . interestingly , tes proximal to genes carry more histone modifications than the ones that are distal to genes , which suggests that some epigenetic modifications of tes may serve to regulate the expression of host genes . dna methylation is a strict silencing mechanism , and the host genome could use this process to repress the activation of tes . in general , because alu and sva elements have a high degree of cpg dinucleotides , they are vulnerable to methylation [ 26 , 62 ] . it was observed that tes regain their activity to mobilize and regulate the expression of host genes when the silencing effect becomes slackened with increasing genomic instability . in addition , the demethylation of tes is associated with human diseases , commonly in cancer [ 63 - 65 ] . mirnas , one of the most active factors regulating gene expression , could be derived from tes . fifty - five genes derived from tes were identified in the human genome , and their characterization showed that te - derived mirnas could potentially regulate the complex and dynamics of human genes . tes have shown a variety of impacts on their host genomes . in this review , we describe herv , alu , l1 , and sva elements , which are thought to still be active in the human genome . a number of research studies related to tes have shed new light on their amplification mechanisms and their function in primate genomes . furthermore , recent research of tes in the rhesus macaque genome provides a glimpse into their diversity and strong influence on the overall differences in genomic architecture between the old world monkey ( e.g. , rhesus macaque ) and hominid ( e.g. , human and ape ) lineages . the occurrence of de novo te insertions , te insertion - mediated deletions , and post - insertion recombination between tes within the human and chimpanzee lineages has caused genetic alteration , lineage - specific genomic rearrangements , and phenotypic variations , further contributing to the divergence of humans and chimpanzees . as a whole , this review calls into question whether tes should be considered " junk " dna at all . rather , tes represent a potent evolutionary force associated with genomic fluidity in their host genomes .
since the advent of whole - genome sequencing , transposable elements ( tes ) , just thought to be ' junk ' dna , have been noticed because of their numerous copies in various eukaryotic genomes . 
 many studies about tes have been conducted to discover their functions in their host genomes . 
 based on the results of those studies , it has been generally accepted that they have a function to cause genomic and genetic variations . however , 
 their infinite functions are not fully elucidated . through various mechanisms , including de novo te insertions , te insertion - mediated deletions , and recombination events , they manipulate their host genomes . in this review , 
 we focus on alu , l1 , human endogenous retrovirus , and short interspersed element / variable number of tandem repeats / alu ( sva ) elements and discuss how they have affected primate genomes , especially the human and chimpanzee genomes , since their divergence .