Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants

Abstract

Rhesus macaque (Macaca mulatta) is a widely-studied nonhuman primate. Here we present a high-quality de novo genome assembly of the Chinese rhesus macaque (rheMacS) using long-read sequencing and multiplatform scaffolding approaches.Compared to the current Indian rhesus macaque reference genome (rheMac8), the rheMacS genome assembly improves sequence contiguity by 75-fold, closing 21,940 of the remaining assembly gaps (60.8 Mbp). To improve gene annotation, we generated more than two million full-length transcripts from ten different tissues by long-read RNA sequencing. We sequence resolve 53,916 structural variants (96% novel) and identify 17,000 ape-specific structural variants (ASSVs) based on comparison to the long-read assembly of ape genomes. We show that many ASSVs map within ChIP-seq predicted enhancer regions where apes and macaque show diverged enhancer activity and gene expression. We further characterize a set of candidate ASSVs that may contribute to ape-or great-ape-specific phenotypic traits, including taillessness, brain volume expansion, improved manual dexterity, and large body size. This improved rheMacS genome assembly serves as an ideal reference for future biomedical and evolutionary studies.

Non-human primates as a model for human development

“…Accordingly, the NHP genomes have been somewhat ''humanized.'' The advance of the long-read DNA sequencer has enabled us to overcome the problems on genome assembly and to identify structural variations among species (He et al, 2019;Kronenberg et al, 2018). There are 17,000 ape-specific structural variants and many of them are located in enhancer regions.…”

Phylogenomic analyses provide insights into primate evolution

“…Understanding the evolution and genetic basis of human-specific traits requires a systematic comparison of genomes along the primate lineages. Previous studies of primate genomes have focused on genomic changes in the human lineage that influenced human brain functions and other traits (120,(153)(154)(155). Our comparative phylogenomic analyses across primate lineages have revealed some of the accumulated genomic changes at different primate ancestral nodes that may have contributed to the evolution of uniquely human traits.…”

“…Although tails vary across the primates in terms of their length and shape, they generally play key roles in relation to locomotion (119). This notwithstanding, the tail was secondarily lost in some primate lineages including the common ancestor of the apes (120,121). We retrieved 151 genes associated with lineage-specific accelerated regions in the common ancestral lineage of the apes (table S33), including KIAA1217 (sickle tail protein homolog) (Figs.…”