Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques.
Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques.
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DOI：
10.1038/nbt.1992
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发表时间：
2011-10-16
影响因子：
46.9
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Yan, Guangmei;Zhang, Guojie;Wang, Jian
医学研究中最常用的非人类灵长类动物来自猕猴属。为了更好地了解这些动物模型之间的遗传差异，我们提供了两种猕猴物种（食蟹猴/食蟹猕猴和中国恒河猴）的高质量基因组序列草案。与之前测序的印度恒河猴进行比较表明，所有三只猕猴都保持着丰富的遗传异质性，包括数百万个单核苷酸替换以及许多插入、缺失和总染色体重排。通过评估变异性降低的遗传区域，我们确定了每个猕猴物种中可能经历过正选择的基因。遗传分化模式表明，食蟹猴基因组是在与中国恒河猴杂交后通过基因渗入而形成的。猕猴基因与人类疾病基因直向同源物和药物靶标具有高度的序列相似性。然而，我们发现这三种猕猴之间存在一些被认为功能失调的遗传差异，这可能解释了之前在临床研究中观察到的它们之间的功能差异。
The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.