Rates and patterns of great ape retrotransposition

Abstract

We analyzed 83 fully sequenced great ape genomes for mobile element insertions, predicting a total of 49,452 fixed and polymorphic Alu and long interspersed element 1 (L1) insertions not present in the human reference assembly and assigning each retrotransposition event to a different time point during great ape evolution. We used these homoplasy-free markers to construct a mobile element insertions-based phylogeny of humans and great apes and demonstrate their differential power to discern ape subspecies and populations. Within this context, we find a good correlation between L1 diversity and single-nucleotide polymorphism heterozygosity (r 2 = 0.65) in contrast to Alu repeats, which show little correlation (r 2 = 0.07). We estimate that the "rate" of Alu retrotransposition has differed by a factor of 15-fold in these lineages. Humans, chimpanzees, and bonobos show the highest rates of Alu accumulation-the latter two since divergence 1.5 Mya. The L1 insertion rate, in contrast, has remained relatively constant, with rates differing by less than a factor of three. We conclude that Alu retrotransposition has been the most variable form of genetic variation during recent human-great ape evolution, with increases and decreases occurring over very short periods of evolutionary time.genomics | genetic diversity | structural variation | retrotransposon M obile elements comprise ∼50% of our genetic code. Among these, Alu (a primate-specific short interspersed element, SINE) and L1 repeats (a long interspersed element, LINE) are the most abundant (1, 2). Both elements propagated in the germ line as a result of target primed reverse transcription (TPRT) using an AP-endonuclease and reverse transcriptase activities encoded by L1 elements (3-5). These integrations-termed "mobile element insertions" (MEIs)-have the potential to disrupt genes, alter transcript expression and splicing, as well as promote genomic instability as a result of nonallelic homologous recombination (6-9). In addition, these MEIs are powerful phylogenetic (10-12) and population genetic markers (13-16) because they are generally regarded as homoplasy-free character states-i.e., precise excision is an exceedingly rare event and, as such, the ancestral and derived state can be unambiguously determined (17)(18)(19)(20).Critical to our understanding of MEI impact with respect to disease and evolution is a detailed assessment of changes in retrotransposition activity within different lineages (21). Genome sequencing comparisons have been used as one method to infer differences in activity between humans and great apes (22-26). There are several important limitations of previous studies. First, genome-wide assessments are generally incomplete because of their dependence on a single representative genome from each species, where consequently the fixed versus polymorphic status of most MEIs is not known. Second, published great ape genome assemblies vary considerably in quality and completeness. The gorilla genome, for example, was assembled primarily from Ill...

Mobile DNA elements in the generation of diversity and complexity in the brain

“…2a). During primate evolution, the rate of Alu retrotransposition was 15-fold higher in human, chimpanzee and bonobo lineages than in gorilla and orangutan lineages 77 . Interestingly, LINE1 activity rates were suppressed in the human lineage compared with chimpanzee and bonobo lineages 77,78 , which may have resulted in a less diverse human population compared to non-human primate populations.…”

“…During primate evolution, the rate of Alu retrotransposition was 15-fold higher in human, chimpanzee and bonobo lineages than in gorilla and orangutan lineages 77 . Interestingly, LINE1 activity rates were suppressed in the human lineage compared with chimpanzee and bonobo lineages 77,78 , which may have resulted in a less diverse human population compared to non-human primate populations. By comparing human and non-human primate induced pluripotent stem cells (iPSCs), it was demonstrated that human iPSCs suppress LINE1 activity, as they have higher levels of Piwi-like protein 2 and APOBEC3B, which are known suppressors of LINE1 retrotransposition 78 .…”

A time- and cost-effective strategy to sequence mammalian Y Chromosomes: an application to the de novo assembly of gorilla Y

“…Cold (Hormozdiari et al 2013). The interspersed repetitive element content on the gorilla Y was different than that for gorilla autosomes (43.3%) and gorilla Chromosome X (52.2%).…”

A genome survey sequencing of the Java mouse deer (Tragulus javanicus) adds new aspects to the evolution of lineage specific retrotransposons in Ruminantia (Cetartiodactyla)

“…Compared to the other two representative of Bovidae, the Tibetan antelope and sheep, BovB is more abundant in the Bovini genome (Table 2). It is known that LINEs can multiply with different success rates in different species (Hormozdiari et al, 2013) and a higher BovB activity could result in higher numbers of BOVA2 SINEs as seen in the lesser kudu genome.…”