Heterozygosity increases microsatellite mutation rate
Heterozygosity increases microsatellite mutation rate
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DOI：
10.1098/rsbl.2015.0929
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发表时间：
2016-01-01
期刊：
影响因子：
3.3
通讯作者：
Amos, William
中科院分区：
文献类型：
--
作者：
Amos, William
拟南芥家族的全基因组测序最近提供了强有力的支持，杂合子不稳定性（HI）的假设，杂合性局部增加突变率。然而，在对碱基取代的影响（其中杂合位点周围区域的突变率增加）与HI对序列（如微卫星）的影响（其中突变可能发生在杂合位点本身）之间存在重要的理论差异。在微卫星位点，HI应形成一个正反馈环，杂合度和突变率相互增加。对作用于微型卫星的HI的直接支持是有限的和矛盾的。因此，我分析了AC微卫星在1163基因组序列从1000基因组计划。我使用了罕见等位基因的存在，这可能是最近的起源，作为突变率的替代措施。我表明，罕见的等位基因更有可能发生在基因座-人口组合具有较高的杂合性，即使所有的人口携带完全相同数量的等位基因。
Whole genome sequencing of families of Arabidopsis has recently lent strong support to the heterozygote instability (HI) hypothesis that heterozygosity locally increases mutation rate. However, there is an important theoretical difference between the impact on base substitutions, where mutation rate increases in regions surrounding a heterozygous site, and the impact of HI on sequences such as microsatellites, where mutations are likely to occur at the heterozygous site itself. At microsatellite loci, HI should create a positive feedback loop, with heterozygosity and mutation rate mutually increasing each other. Direct support for HI acting on microsatellites is limited and contradictory. I therefore analysed AC microsatellites in 1163 genome sequences from the 1000 genomes project. I used the presence of rare alleles, which are likely to be very recent in origin, as a surrogate measure of mutation rate. I show that rare alleles are more likely to occur at locus-population combinations with higher heterozygosity even when all populations carry exactly the same number of alleles.