Yoo DongAhn, Munson Katherine M, Eichler Evan E
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.
Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
bioRxiv. 2025 May 30:2025.05.29.656835. doi: 10.1101/2025.05.29.656835.
Many African great ape chromosomes possess large subterminal heterochromatic caps at their telomeres that are conspicuously absent from the human lineage. Leveraging the complete sequences of great ape genomes, we characterize the organization of subterminal caps and reconstruct the evolutionary history of these regions in chimpanzees and gorillas. Detailed analyses of the pCht satellite composition and associated segmental duplication (SD) spacers confirm two independent origins in the and gorilla lineages. In chimpanzee and bonobo, we estimate these structures emerged ~7.5 million years ago (MYA) in contrast to gorilla where they expanded more recently ~5.1 MYA and now make up 8.5% of the total gorilla genome. In both lineages, the SD spacers punctuating the pCht heterochromatic satellite arrays correspond to pockets of hypomethylation, although in gorilla such regions are significantly more hypomethylated (<2.2e-16) than chimpanzee or bonobo. Allelic pairs of subterminal caps show a high degree of sequence divergence (9-11%) with bonobo showing less divergent haplotypes and less hypomethylated spacers. In contrast, we identify virtually identical subterminal caps mapping to nonhomologous chromosomes within a species, suggesting ectopic recombination potentially mediated by SD spacers. We find that the transition regions from heterochromatic subterminal caps to euchromatin are enriched for structural variant insertions and lineage-specific duplicated genes. We suggest these regions are hotspots for accelerating ape genome evolution.
许多非洲大猿的染色体在其端粒处拥有大的亚末端异染色质帽，而人类谱系中则明显没有。利用大猿基因组的完整序列，我们对亚末端帽的组织进行了表征，并重建了黑猩猩和大猩猩这些区域的进化历史。对pCht卫星组成和相关节段性重复（SD）间隔区的详细分析证实了在黑猩猩和大猩猩谱系中有两个独立的起源。在黑猩猩和倭黑猩猩中，我们估计这些结构在约750万年前（MYA）出现，而在大猩猩中它们最近在约510万年前扩张，现在占大猩猩基因组总量的8.5%。在这两个谱系中，打断pCht异染色质卫星阵列的SD间隔区对应于低甲基化区域，尽管在大猩猩中这些区域的低甲基化程度（<2.2e - 16）明显高于黑猩猩或倭黑猩猩。亚末端帽的等位基因对显示出高度的序列分歧（9 - 11%），倭黑猩猩的单倍型分歧较小且间隔区的低甲基化程度较低。相比之下，我们在一个物种内发现映射到非同源染色体上的几乎相同的亚末端帽，这表明可能由SD间隔区介导的异位重组。我们发现从异染色质亚末端帽到常染色质的过渡区域富含结构变异插入和谱系特异性重复基因。我们认为这些区域是加速猿类基因组进化的热点。
