A view of Neandertal genetic diversity
A view of Neandertal genetic diversity
复制标题
DOI：
10.1038/79855
复制
发表时间：
2000-10-01
期刊：
影响因子：
30.8
通讯作者：
Pääbo, S
中科院分区：
文献类型：
--
作者：
Krings, M;Capelli, C;Pääbo, S
2000 Nature America Inc.·http：//genetics.自然自然遗传学·第26卷·2000年10月145人类和尼安德特人的DNA序列（从模式标本中确定）被扩增，我们经常观察到克隆类似于尼安德特人的mtDNA序列以及克隆类似于当代人类的mtDNA序列。在这些情况下，前一类序列被认为是化石的内源性。在7个扩增提取PTB已被使用，我们发现27个克隆携带尼安德特人序列和64携带当代人类序列，而在两个扩增提取没有PTB已被使用，所有20个克隆测序携带人类DNA序列。因此，PTB似乎特别有助于从骨骼中检索古代DNA。按照既定的策略1，从Vindija 75化石中重建了357 bp的高变区（HVR）-1和288 bp的HVR-2（图A，参见http：//genetics.自然com/supplementary_info/）。与模式标本序列相比，它们在HVR-2中存在9个取代以及一段胞嘧啶和胸苷残基的长度上存在差异。来自两个尼安德特人的序列与来自世界各地的663名现代人的序列不同，有34.9±2.4个取代，并且插入了两个尼安德特人共有的腺苷残基。它们与欧洲的472个现代mtDNA（35.3±2.1，范围29-43）相比，并不更接近，例如，151个非洲人（33.9±2.8，范围28-42）或41个亚洲人（33.5±2.1，范围29-38）。这反映在基因树中，两个尼安德特人聚集在一起，排除了所有现代人（图1a）。这些结果并不排除尼安德特人和现代人之间可能发生了杂交，但它们表明，即使发生了杂交，尼安德特人最终也没有为当代人类基因库贡献mtDNA。最近确定的345 bp的HVR-1区域从Mezmaiskaya洞穴3的尼安德特人，使得有可能估计三个尼安德特人之间的遗传多样性。虽然这代表了一个非常小的样本量，但值得注意的是，在随机交配群体中采样最深遗传分歧的概率是n-1/n+ 1，其中n是采样个体的数量10。原则上，三个尼安德特人序列因此允许50%的概率采样尼安德特人之间最深的分歧。事实上，这可能是一个保守的估计，因为样本在地理上和时间上都是高度分散的。一个基于距离的树与三个序列进行了估计，并在这棵树中的位置发生了变化的百分比作为衡量尼安德特人mtDNA多样性。为了与现代人进行比较，我们估计了与从数据库中可用的5，530个现代人确定的DNA序列中随机选择的总共50，000个三联体序列相关的树11。然后对359只普通黑猩猩和28只大猩猩进行了同样的分析（图1b-d和表1）。3种尼安德特人mtDNA的多样性（3.73%）低于黑猩猩（14.82±5.70%）和大猩猩（18.57±5.26%），与世界范围内现代人的多样性（3.43±1.22%）相近。当人类序列被分类到大陆群体中时，三个尼安德特人之间的多样性与非洲人、亚洲人、美洲原住民、澳大利亚原住民和大洋洲原住民之间的差异在一个标准差之内。
2000 Nature America Inc.• http://g enetics. nature. com brief communications nature genetics• volume 26• october 2000 145 human and Neandertal DNA sequences (as determined from the type specimen) to be amplified, we often observed clones similar to the Neandertal mtDNA sequences as well as clones similar to contemporary human mtDNA sequences. In those cases, the former class of sequences was deemed to be endogenous to the fossil. In seven amplifications performed from extractions in which PTB had been used, we found 27 clones carrying Neandertal sequences and 64 carrying contemporary human sequences, whereas in two amplifications from extractions in which no PTB had been used, all 20 clones sequenced carried human DNA sequences. Thus, PTB seems to specifically facilitate the retrieval of ancient DNA also from bones. Following an established strategy1, 357 bp of the hypervariable region (HVR)-1 and 288 bp of the HVR-2 were reconstructed from the Vindija 75 fossil (Fig. A, see http://genetics. nature. com/supplementary_info/). When compared with the type specimen sequence, they differed by nine substitutions and in the length of a stretch of cytosine and thymide residues in HVR-2. The sequences from the two Neandertals differ from those of 663 modern humans sampled from all areas of the world by 34.9±2.4 substitutions and by an insertion of an adenosine residue shared by the two Neandertals. They are not closer to 472 contemporary mtDNAs in Europe (35.3±2.1, range 29–43), the area where they existed until approximately 30,000 years ago, than to, for example, 151 African (33.9±2.8, range 28–42) or 41 Asian mtDNAs (33.5±2.1, range 29–38). This is reflected in a gene tree, where the two Neandertals group together to the exclusion of all modern humans (Fig. 1a). These results do not exclude that interbreeding between Neandertals and modern humans may have taken place9, but they show that even if it occurred, Neandertals did not end up contributing mtDNA to the contemporary human gene pool. The recent determination of 345 bp of the HVR-1 region from a Neandertal from Mezmaiskaya Cave3 makes it possible to estimate the genetic diversity among three Neandertals. Although this represents a very small sample size, it is worth noting that the probability of sampling the deepest genetic divergence in a randomly mating population is n–1/n+ 1, where n is the number of sampled individuals10. In principle, the three Neandertal sequences therefore allow a probability of 50% to sample the deepest divergence among Neandertals. In fact, this is likely to be a conservative estimate because the samples are highly dispersed both geographically and temporally. A distance-based tree relating the three sequences was estimated, and the per cent of positions that have changed in this tree taken as a measure of Neandertal mtDNA diversity. To compare this with modern humans, we estimated trees relating a total of 50,000 triplets of sequences randomly chosen among DNA sequences determined from 5,530 modern humans available in the database11. The same analysis was then performed for 359 common chimpanzees and 28 gorillas (Fig. 1b–d and Table 1). The diversity of the three Neandertal mtDNAs (3.73%) was lower than that of chimpanzees (14.82±5.70%) and gorillas (18.57±5.26%) and similar to that of modern humans worldwide (3.43±1.22%). When the human sequences were sorted into continental groups, the diversity among the three Neandertals fell within one standard deviation of the variation for Africans, Asians, Native Americans, and aboriginal Australians and Oceanians, whereas …