Heterozygosity increases microsatellite mutation rate, linking it to demographic history.
Heterozygosity increases microsatellite mutation rate, linking it to demographic history.
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DOI：
10.1186/1471-2156-9-72
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发表时间：
2008-11-14
期刊：
影响因子：
2.9
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Amos W;Flint J;Xu X
酵母中的生化实验表明了一种可能的机制，该机制会导致杂合位点比同等的纯合位点突变得更快。如果这样的过程发生，它可能会破坏种群遗传理论核心的一个关键假设，即突变率和种群规模是独立的，因为种群扩张会增加杂合性，进而增加突变率。在这里，我们使用人类谱系中微卫星突变的直接计数以及微卫星长度与人口统计诱导的杂合性变异模式之间关系的分析来检验这一假设。我们发现，当同源物的长度异常不同时，任何给定长度的微卫星等位基因更有可能发生突变。此外，人类群体中的微卫星长度并不是随机变化的，而是随着距非洲的距离（全基因组杂合性的替代测量）和现代人口规模而表现出高度可预测的趋势。即使在统计上控制了由于人群之间有共同血统而导致的非独立性之后，这种可预测性仍然存在。我们的结果揭示了经典群体遗传理论中意想不到的模式，其中不存在能够将等位基因长度与地理或群体规模等外在变量联系起来的机制。然而，微卫星长度的可预测性与杂合子的不稳定性是一致的，表明这对微卫星的进化具有重要影响。类似的过程是否影响单核苷酸多态性仍不清楚。
Biochemical experiments in yeast suggest a possible mechanism that would cause heterozygous sites to mutate faster than equivalent homozygous sites. If such a process operates, it could undermine a key assumption at the core of population genetic theory, namely that mutation rate and population size are indpendent, because population expansion would increase heterozygosity that in turn would increase mutation rate. Here we test this hypothesis using both direct counting of microsatellite mutations in human pedigrees and an analysis of the relationship between microsatellite length and patterns of demographically-induced variation in heterozygosity. We find that microsatellite alleles of any given length are more likely to mutate when their homologue is unusually different in length. Furthermore, microsatellite lengths in human populations do not vary randomly, but instead exhibit highly predictable trends with both distance from Africa, a surrogate measure of genome-wide heterozygosity, and modern population size. This predictability remains even after statistically controlling for non-independence due to shared ancestry among populations. Our results reveal patterns that are unexpected under classical population genetic theory, where no mechanism exists capable of linking allele length to extrinsic variables such as geography or population size. However, the predictability of microsatellite length is consistent with heterozygote instability and suggest that this has an important impact on microsatellite evolution. Whether similar processes impact on single nucleotide polymorphisms remains unclear.
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影响因子：
7
作者：
Kelkar, Yogeshwar D.;Tyekucheva, Svitlana;Makova, Kateryna D.
通讯作者：
Makova, Kateryna D.
影响因子：
3.5
作者：
WEBER, JL;WONG, C
通讯作者：
WONG, C
DOI：
10.1073/pnas.91.8.3166
发表时间：
1994-04-12
影响因子：
11.1
作者：
DIRIENZO, A;PETERSON, AC;FREIMER, NB
通讯作者：
FREIMER, NB
DOI：
10.1073/pnas.0507611102
发表时间：
2005-11-01
影响因子：
11.1
作者：
Ramachandran, S;Deshpande, O;Cavalli-Sforza, LL
通讯作者：
Cavalli-Sforza, LL
影响因子：
4.4
作者：
WEBER, JL
通讯作者：
WEBER, JL