Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection
Trans genomic capture and sequencing of primate exomes reveals new targets of positive selection
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DOI：
10.1101/gr.121327.111
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发表时间：
2011-10-01
期刊：
影响因子：
7
通讯作者：
Thomas, James H.
中科院分区：
文献类型：
--
作者：
George, Renee D.;McVicker, Graham;Thomas, James H.
比较不同灵长类动物的蛋白质编码DNA序列可以深入了解这些物种的进化历史，并揭示其表型差异的分子基础。目前，可用的灵长类动物参考基因组的数量限制了这些全基因组比较。在这里，我们使用为人类设计的靶向捕获方法对四种非人类灵长类动物物种（三种旧世界猴和一种新世界猴）的蛋白质编码区或外显子组进行测序。尽管与人类序列探针的平均序列差异高达4%，但我们能够捕获类似于96%的编码序列。使用映射和组装技术的组合，我们为每个物种生成了高质量的全长编码序列。核苷酸差异的数量和插入和缺失（indel）长度的分布表明，组装序列的质量非常高，超过了大多数参考基因组。使用这组扩展的灵长类动物编码序列，我们对经历正选择的基因进行了全基因组扫描，并确定了一类新的适应性进化基因，这些基因参与皮肤、头发和指甲中上皮细胞向角蛋白的转化。有趣的是，我们在正选择下发现的基因在人群中也表现出显着增加的等位基因频率差异，这表明它们在近期和长期适应中发挥作用。我们还确定了几个基因，已经失去了特定的灵长类动物谱系，这说明了广泛的实用程序，其他进化分析的数据集。这些结果证明了第二代测序在比较基因组学中的作用，并极大地扩展了现有灵长类动物编码序列的库。
Comparison of protein-coding DNA sequences from diverse primates can provide insight into these species' evolutionary history and uncover the molecular basis for their phenotypic differences. Currently, the number of available primate reference genomes limits these genome-wide comparisons. Here we use targeted capture methods designed for human to sequence the protein-coding regions, or exomes, of four non-human primate species (three Old World monkeys and one New World monkey). Despite average sequence divergence of up to 4% from the human sequence probes, we are able to capture similar to 96% of coding sequences. Using a combination of mapping and assembly techniques, we generated high-quality full-length coding sequences for each species. Both the number of nucleotide differences and the distribution of insertion and deletion (indel) lengths indicate that the quality of the assembled sequences is very high and exceeds that of most reference genomes. Using this expanded set of primate coding sequences, we performed a genome-wide scan for genes experiencing positive selection and identified a novel class of adaptively evolving genes involved in the conversion of epithelial cells in skin, hair, and nails to keratin. Interestingly, the genes we identify under positive selection also exhibit significantly increased allele frequency differences among human populations, suggesting that they play a role in both recent and long-term adaptation. We also identify several genes that have been lost on specific primate lineages, which illustrate the broad utility of this data set for other evolutionary analyses. These results demonstrate the power of second-generation sequencing in comparative genomics and greatly expand the repertoire of available primate coding sequences.