Sequencing and analysis of Neanderthal genomic DNA
Sequencing and analysis of Neanderthal genomic DNA
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DOI：
10.1126/science.1131412
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发表时间：
2006-11-17
期刊：
影响因子：
56.9
通讯作者：
Rubin, Edward M.
中科院分区：
文献类型：
--
作者：
Noonan, James P.;Coop, Graham;Rubin, Edward M.
我们对尼安德特人的了解基于数量有限的遗骸和文物，我们必须从这些遗骸和文物中对他们的生物学特征、行为以及与我们自身的关系进行推断。在此，我们基于尼安德特人宏基因组文库的建立及其高通量测序和分析，从一个新的视角描述了这些已灭绝的原始人类的特征。几条证据表明，到目前为止在文库中确定的65250对原始人类序列碱基是尼安德特人的，最有力的证据是在人类基因组序列不同的位点确定了尼安德特人和黑猩猩之间的序列一致性。这些结果使我们能够基于多个随机分布的常染色体位点计算人类与尼安德特人的分化时间。我们的分析表明，平均而言，我们获得的尼安德特人基因组序列与参考人类基因组序列拥有一个大约70.6万年前的最近共同祖先，并且人类和尼安德特人的祖先群体大约在37万年前，也就是在解剖学上的现代人类出现之前就已经分化。我们发现尼安德特人和人类的基因组至少有99.5%是相同的，这使我们开发并成功实施了一种从宏基因组文库中恢复特定古代DNA序列的靶向方法。对尼安德特人基因组的这一初步分析增进了我们对智人与尼安德特人进化关系的理解，并标志着尼安德特人基因组学的开端。
Our knowledge of Neanderthals is based on a limited number of remains and artifacts from which we must make inferences about their biology, behavior, and relationship to ourselves. Here, we describe the characterization of these extinct hominids from a new perspective, based on the development of a Neanderthal metagenomic library and its high-throughput sequencing and analysis. Several lines of evidence indicate that the 65,250 base pairs of hominid sequence so far identified in the library are of Neanderthal origin, the strongest being the ascertainment of sequence identities between Neanderthal and chimpanzee at sites where the human genomic sequence is different. These results enabled us to calculate the human-Neanderthal divergence time based on multiple randomly distributed autosomal loci. Our analyses suggest that on average the Neanderthal genomic sequence we obtained and the reference human genome sequence share a most recent common ancestor similar to 706,000 years ago, and that the human and Neanderthal ancestral populations split similar to 370,000 years ago, before the emergence of anatomically modern humans. Our finding that the Neanderthal and human genomes are at least 99.5% identical led us to develop and successfully implement a targeted method for recovering specific ancient DNA sequences from metagenomic libraries. This initial analysis of the Neanderthal genome advances our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signifies the dawn of Neanderthal genomics.