Slow molecular clocks in Old World monkeys, apes, and humans
Slow molecular clocks in Old World monkeys, apes, and humans
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DOI：
10.1093/oxfordjournals.molbev.a004043
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发表时间：
2002-12-01
影响因子：
10.7
通讯作者：
Li, WH
中科院分区：
文献类型：
--
作者：
Yi, SJ;Ellsworth, DL;Li, WH
本文研究了分子钟假说中两个长期存在的问题。第一，哺乳动物体内是否存在一个全球性的分子钟？虽然许多作者已经观察到哺乳动物谱系之间的核苷酸取代率不相等，但一些作者提出了所有真兽目动物的全球时钟，即，每年每个核苷酸位点2.2 × 10（-9）个替换的单一全局速率。我们重新审视这个问题，使用非编码，非重复的DNA从旧世界的猴子（OWM），黑猩猩，和人类。首先，使用人类与黑猩猩分歧的最小日期6百万年，以及来自人类和黑猩猩的超过250万个碱基对的基因组序列，我们估计这两个物种的非编码、非重复基因组区域的最大比率为0.99 × 10（-9）。这一估计值不到拟议的全球比率的一半，并且远小于真兽目动物常用的比率（13.5 × 10（-9））。此外，使用23 MYA的人类-OWM分歧的最小日期，我们估计在人类和OWM中内含子和四倍简并位点的最大比率为1.5 × 10（-9）。此外，与新世界猴（NWM）谱系作为外群，我们估计，在内含子的替代率是30%，在OWM谱系比在人类谱系。显然，真兽目动物中没有全局分子钟。第二，尽管许多研究表明哺乳动物基因组各区域的突变率有相当大的差异，但最近的一项研究提出了一个统一的比率。使用新的和现有的内含子序列数据从高等灵长类动物，我们发现显着的基因组区域之间的变化率和取代率和GC含量之间的正相关性，驳斥了统一率的说法。
Two longstanding issues on the molecular clock hypothesis are studied in this article. First, is there a global molecular clock in mammals? Although many authors have observed unequal rates of nucleotide substitution among mammalian lineages, some authors have proposed a global clock for all eutherians, i.e., a single global rate of 2.2 X 10(-9) substitutions per nucleotide site per year. We reexamine this issue using noncoding, nonrepetitive DNA from Old World monkeys (OWMs), chimpanzee, and human. First, using the minimal date of 6 MYA for the human-chimpanzee divergence and more than 2.5 million base pairs of genomic sequences from human and chimpanzee, we estimate a maximal rate of 0.99 X 10(-9) for noncoding, nonrepetitive genomic regions for these two species. This estimate is less than half of the proposed global rate and much smaller than the commonly used rate (13.5 X 10(-9)) for eutherians. Further, using a minimal date of 23 MYA for the human-OWM divergence, we estimate a maximal rate of 1.5 X 10(-9) for both introns and fourfold degenerate sites in humans and OWMs. In addition, with the New World monkey (NWM) lineage as an outgroup, we estimate that the rate of substitution in introns is 30% higher in the OWM lineage than in the human lineage. Clearly, there is no global molecular clock in eutherians. Second, although many studies have indicated considerable variation in the mutation rate among regions of the mammalian genome, a recent study proposed a uniform rate. Using new and existing intron sequence data from higher primates, we find significant rate variation among genomic regions and a positive correlation between the rate of substitution and the GC content, refuting the claim of a uniform rate.