Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1.
Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1.
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1 号染色体 10 kb 区域中人类 DNA 序列变异的全局模式。
DOI：
10.1093/oxfordjournals.molbev.a003795
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发表时间：
2001
影响因子：
10.7
通讯作者：
Li,WH
中科院分区：
文献类型：
--
作者：
Yu,N;Zhao,Z;Fu,YX;Sambuughin,N;Ramsay,M;Jenkins,T;Leskinen,E;Patthy,L;Jorde,LB;Kuromori,T;Li,WH
人类DNA变异目前是一个密集的研究主题，因为它对研究人类起源、进化和人口学历史以及复杂疾病的相关性研究具有重要意义。测定了61名人类(20名非洲人、20名亚洲人和21名欧洲人)、1只黑猩猩、1只大猩猩和1只猩猩的1号染色体上的∼10kb区域，它只包含4个小外显子(每个外显子155bp)。我们在122个人类序列中发现了52个多态位点，在人类、黑猩猩、大猩猩和猩猩的序列中发现了382个变异位点。测序内含子(8,991bp)，核苷酸多样性(π)在所有序列中为0.058%，在非洲序列中为0.076%，在亚洲序列中为0.047%，在欧洲序列中为0.045%。数据汇编显示，常染色体区域的π值平均最高(0.091%)，X连锁区域的π值稍低(0.079%)，Y连锁区域的π值非常低(0.008%)。本区域较低的多态可能是由于含有这些内含子的基因或与该区域连锁的基因的突变率和/或选择较低。本区域和另外两个10kb的非编码区都显示出大量的低频变异，表明相对最近的种群扩张。该区域的突变率较低，估计为每核苷酸每年0.74×10个。使用各种方法得出长期有效人口规模的平均估计值∼为12,600；这一估计值与通常使用的10,000个数值相差不远。Fu和Li的测试否定了平衡中性Wright-Fisher群体的假设，这主要是因为低频变异的比例很高。我们样本中序列的最新共同祖先的年龄估计超过1 Myr。考虑到模型中一些不切实际的假设，这一估计仍然表明人类的年龄超过50万年，这为人类的遗传史提供了进一步的证据，这比现代人类的出现要古老得多。欧洲和亚洲存在许多独特的变异，这一事实也表明非洲以外有相当长的遗传历史，并反对用一小部分非洲种群完全取代欧洲和亚洲的所有土著人口。此外，人类的古代遗传史表明，在过去50万年的人类进化过程中，没有严重的瓶颈；否则，古代遗传史的大部分都会在严重的瓶颈中丢失。我们认为，无论是“走出非洲”模型还是多区域模型都过于简单，无法解释现代人的进化。
Human DNA variation is currently a subject of intense research because of its importance for studying human origins, evolution, and demographic history and for association studies of complex diseases. A ∼10-kb region on chromosome 1, which contains only four small exons (each <155 bp), was sequenced for 61 humans (20 Africans, 20 Asians, and 21 Europeans) and for 1 chimpanzee, 1 gorilla, and 1 orangutan. We found 52 polymorphic sites among the 122 human sequences and 382 variant sites among the human, chimpanzee, gorilla, and orangutan sequences. For the introns sequenced (8,991 bp), the nucleotide diversity (π) was 0.058% among all sequences, 0.076% among the African sequences, 0.047% among the Asian sequences, and 0.045% among the European sequences. A compilation of data revealed that autosomal regions have, on average, the highest π value (0.091%), X-linked regions have a somewhat lower π value (0.079%), and Y-linked regions have a very low π value (0.008%). The lower polymorphism in the present region may be due to a lower mutation rate and/or selection in the gene containing these introns or in genes linked to this region. The present region and two other 10-kb noncoding regions all show a strong excess of low-frequency variants, indicating a relatively recent population expansion. This region has a low mutation rate, which was estimated to be 0.74 × 10 per nucleotide per year. An average estimate of ∼12,600 for the long-term effective population size was obtained using various methods; the estimate was not far from the commonly used value of 10,000. Fu and Li's tests rejected the assumption of an equilibrium neutral Wright-Fisher population, largely owing to the high proportion of low-frequency variants. The age of the most recent common ancestor of the sequences in our sample was estimated to be more than 1 Myr. Allowing for some unrealistic assumptions in the model, this estimate would still suggest an age of more than 500,000 years, providing further evidence for a genetic history of humans much more ancient than the emergence of modern humans. The fact that many unique variants exist in Europe and Asia also suggests a fairly long genetic history outside of Africa and argues against a complete replacement of all indigenous populations in Europe and Asia by a small Africa stock. Moreover, the ancient genetic history of humans indicates no severe bottleneck during the evolution of humans in the last half million years; otherwise, much of the ancient genetic history would have been lost during a severe bottleneck. We suggest that both the “Out of Africa” and the multiregional models are too simple to explain the evolution of modern humans.