Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, South Korea.
Comparative Biomedical Science Department, Royal Veterinary College, University of London, London, NW1 0TU, United Kingdom.
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5379-E5388. doi: 10.1073/pnas.1702012114. Epub 2017 Jun 19.
Whole-genome assemblies of 19 placental mammals and two outgroup species were used to reconstruct the order and orientation of syntenic fragments in chromosomes of the eutherian ancestor and six other descendant ancestors leading to human. For ancestral chromosome reconstructions, we developed an algorithm (DESCHRAMBLER) that probabilistically determines the adjacencies of syntenic fragments using chromosome-scale and fragmented genome assemblies. The reconstructed chromosomes of the eutherian, boreoeutherian, and euarchontoglires ancestor each included >80% of the entire length of the human genome, whereas reconstructed chromosomes of the most recent common ancestor of simians, catarrhini, great apes, and humans and chimpanzees included >90% of human genome sequence. These high-coverage reconstructions permitted reliable identification of chromosomal rearrangements over ∼105 My of eutherian evolution. Orangutan was found to have eight chromosomes that were completely conserved in homologous sequence order and orientation with the eutherian ancestor, the largest number for any species. Ruminant artiodactyls had the highest frequency of intrachromosomal rearrangements, and interchromosomal rearrangements dominated in murid rodents. A total of 162 chromosomal breakpoints in evolution of the eutherian ancestral genome to the human genome were identified; however, the rate of rearrangements was significantly lower (0.80/My) during the first ∼60 My of eutherian evolution, then increased to greater than 2.0/My along the five primate lineages studied. Our results significantly expand knowledge of eutherian genome evolution and will facilitate greater understanding of the role of chromosome rearrangements in adaptation, speciation, and the etiology of inherited and spontaneously occurring diseases.
使用 19 种胎盘哺乳动物和 2 种外群物种的全基因组组装，重建了真兽类祖先和导致人类的其他 6 个后裔祖先的染色体中同线性片段的顺序和方向。对于祖先染色体重建，我们开发了一种算法（DESCHRAMBLER），该算法使用染色体尺度和碎片化基因组组装来概率确定同线性片段的邻接关系。重建的真兽类、北方真兽类和真兽类祖先的染色体各自包含人类基因组全长的>80%，而灵长类动物、灵长类动物、巨猿和人类和黑猩猩的最近共同祖先的重建染色体包含人类基因组序列的>90%。这些高覆盖率的重建允许可靠地识别在>105 万年的真兽类进化过程中的染色体重排。发现猩猩有 8 条染色体与真兽类祖先在同源序列顺序和方向上完全保守，是任何物种中最多的。反刍偶蹄动物的染色体内重排频率最高，而染色体间重排则在鼠形啮齿动物中占主导地位。在真兽类祖先基因组向人类基因组的进化过程中，共鉴定出 162 个染色体断点；然而，在真兽类进化的前约 60 万年，重排的速度显著降低（0.80/My），然后沿着研究的五个灵长类谱系增加到大于 2.0/My。我们的研究结果显著扩展了真兽类基因组进化的知识，并将有助于更好地理解染色体重排在适应、物种形成和遗传和自发发生疾病的病因中的作用。
