| 其他摘要 | As the closest relatives of humans, nonhuman primates are of great importance and irreplaceable as animal models. However, comparisons based on the genome sequences among nonhuman primates are still limited. Although the genome assemblies of chimpanzee, gorilla and Indian rhesus macaque (IR) have been released, the use of these primate species in biomedical research is rather limited. In constrast, the other two nonhuman primate species-Chinese rhesus macaque (CR) and crab-eating macaque (CE) are the most widely used nonhuman primate models, but their genomes are still undecoded. In this study, we aim to understand 1) the genetic difference beween CR and IR using the next-generation sequencing at the genome-wide level. Additionally, based on the de novo assembly of CR and CE genomes, we carried out genome comparison between the species/subspecies in the macaca genus, and we also conducted comparative transcriptome analysis among them. We uncovered a wealth of sequence diversity and structural variation (SV) between CR and IR, although they are classified as subspecies. Totally, we identified 5.5 million single nucleotide polymorphisms (SNPs) with density of 2.08 per kilobase (kb). Meanwhile, we also identified a total of 125,150 SVs, where 98.8% of them are deletions. Using PCR-direct sequencing verification, we confirmed the accuracy of the identified SVs between CR and IR. Next, using ultra-deep sequencing, we de novo assembled the CR and CE genomes (47X and 54X coverage, respectively). The results indicated the mostly diverged genomes are observed between CE and IR. The genetic divergence between CR and CE is close to that of CR and IR. Further hybridization model analysis suggested that the genetic introgression from CR to CE occurred long time ago. Moreover, comparison based on the disease-related genes and the druggable target orthologs indicated that these animal models are likely to be functionally equivalent. Nonetheless, we also discovered a few cases showing difference among species/subspecies. For example, TRIM5α, the gene encoding a protein performing restrictions in HIV and SIV replication contains a 6 bp deletion (encoding Thr339 and Phe340) polymorphism and the frequencies among the macaques are significantly different, suggesting that it is necessary to consider genetic divergence of macaques for constructing virus or immunological disease models. Finally, our comparative transcriptome analysis between CE and IR based on RNA-seq indicated that the gene expression parttern in testes is the mostly diverged among the tissues tested, implying the act of sexual selection leading to rapid evolution of the expression profile in these primate species. |
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