Structurally divergent and recurrently mutated regions of primate genomes

Abstract

To better understand the pattern of primate genome structural variation, we sequenced and assembled using multiple long-read sequencing technologies the genomes of eight nonhuman primate species, including New World monkeys (owl monkey and marmoset), Old World monkey (macaque), Asian apes (orangutan and gibbon), and African ape lineages (gorilla, bonobo, and chimpanzee). Compared to the human genome, we identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. Across 50 million years of primate evolution, we estimate that 819.47 Mbp or ~27% of the genome has been affected by SVs based on analysis of these primate lineages. We identify 1,607 structurally divergent regions (SDRs) wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (CARDs, ABCD7, OLAH) and new lineage-specific genes are generated (e.g., CKAP2, NEK5) and have become targets of rapid chromosomal diversification and positive selection (e.g., RGPDs). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species for the first time.

LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification

“…We found that the L1PA2 insertion site is present-and identical-in human, chimpanzee, bonobo, and gorilla, but not in orangutan, macaque, or other lower species (Fig. 5F) (49). Thus, this L1PA2 insertion can be estimated to have occurred around 10 to 20 million years ago.…”

“…Denisova and Neanderthal genomes both displayed the human variant, suggesting that the nucleotide change occurred before the split of archaic human species (Fig. 5F) (49). This analysis indicated that it is possible that the L1-lncRNA promoter may be silenced by DNA methylation or other repressive factors in nonhuman primates due to the expression and translation of an ORF0-fusion-transcript.…”

RANBP2 evolution and human disease

“…Besides humans, only gibbons, orangutans, gorillas, bonobos, and chimpanzees encode for RGPDs . There is no evidence of RGPD ‐like genes in any other primate or mammal [77]. Each ape species encodes for a different set of RGPD genes: one copy in gibbons, three in orangutans, four in gorillas, six in chimpanzees, and seven in humans (i.e., RGPD1‐8 without any RGPD7).…”

“…Each ape species encodes for a different set of RGPD genes: one copy in gibbons, three in orangutans, four in gorillas, six in chimpanzees, and seven in humans (i.e., RGPD1‐8 without any RGPD7). Strikingly, a recent study revealed that the multiple copies of RGPD arose mostly independently in the five different ape lineages, which constitutes an extreme example of homoplasy [77]. Only RGPD2 in African great apes (gorillas, chimpanzees, and humans) appears syntenic and orthologous.…”

“…Only RGPD2 in African great apes (gorillas, chimpanzees, and humans) appears syntenic and orthologous. Human RGPD5 , RGPD6 , and RGPD8 are closely related, and RGPD6 is a human‐specific gene copy that has arisen from RGPD5 as the most recent duplication event (~ 5.2 kya [77]). Remarkably, the high nucleotide identity between RGPD5 and RGPD6 has led to predisposition of inversion and microdeletion between these two genes.…”