Overdominant Mutations Restrict Adaptive Loss of Heterozygosity at Linked Loci.
Overdominant Mutations Restrict Adaptive Loss of Heterozygosity at Linked Loci.
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DOI：
10.1093/gbe/evab181
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发表时间：
2021-08-03
影响因子：
3.3
通讯作者：
Lang GI
中科院分区：
文献类型：
--
作者：
Fisher KJ;Vignogna RC;Lang GI
杂合性丢失是无性二倍体群体中常见的适应模式。由于有丝分裂重组经常延长染色体臂的全长，杂合性丢失的选择性益处可能受到连锁杂合突变的限制。在先前的二倍体酵母的实验室进化实验中，我们经常观察到染色体XV右臂上WHI 2基因的纯合突变。然而，当杂合突变出现在STE 4基因，另一个常见的目标染色体XV，在WHI 2的杂合性丢失没有观察到。在这里，我们发现WHI 2突变是部分显性的，而STE 4突变是超显性的。我们测试是否有益的杂合突变在这两个位点相互干扰，通过测量的杂合性丢失WHI 2超过1,000代的1,000个人口，最初只在STE 4和WHI 2不同。我们表明，STE 4中存在的显性突变减少，但不能消除，在WHI 2的杂合性丢失。通过对40个进化的克隆进行测序，我们发现，具有连锁超显性和部分显性突变的群体在基因水平上表现出较少的平行性，更多样化的进化结果，以及非整倍体率的增加。我们的研究结果表明，优势的程度和杂合有益突变的定相可以限制杂合性丢失沿着染色体臂，部分显性和超显性突变之间的冲突可以影响进化的结果。
Loss of heterozygosity is a common mode of adaptation in asexual diploid populations. Because mitotic recombination frequently extends the full length of a chromosome arm, the selective benefit of loss of heterozygosity may be constrained by linked heterozygous mutations. In a previous laboratory evolution experiment with diploid yeast, we frequently observed homozygous mutations in the WHI2 gene on the right arm of Chromosome XV. However, when heterozygous mutations arose in the STE4 gene, another common target on Chromosome XV, loss of heterozygosity at WHI2 was not observed. Here, we show that mutations at WHI2 are partially dominant and that mutations at STE4 are overdominant. We test whether beneficial heterozygous mutations at these two loci interfere with one another by measuring loss of heterozygosity at WHI2 over 1,000 generations for ∼300 populations that differed initially only at STE4 and WHI2. We show that the presence of an overdominant mutation in STE4 reduces, but does not eliminate, loss of heterozygosity at WHI2. By sequencing 40 evolved clones, we show that populations with linked overdominant and partially dominant mutations show less parallelism at the gene level, more varied evolutionary outcomes, and increased rates of aneuploidy. Our results show that the degree of dominance and the phasing of heterozygous beneficial mutations can constrain loss of heterozygosity along a chromosome arm, and that conflicts between partially dominant and overdominant mutations can affect evolutionary outcomes.
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