Loss-of-heterozygosity facilitates passage through Haldane's sieve for Saccharomyces cerevisiae undergoing adaptation
Loss-of-heterozygosity facilitates passage through Haldane's sieve for Saccharomyces cerevisiae undergoing adaptation
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DOI：
10.1038/ncomms4819
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发表时间：
2014-05-01
影响因子：
16.6
通讯作者：
Otto, S. P.
中科院分区：
文献类型：
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作者：
Gerstein, A. C.;Kuzmin, A.;Otto, S. P.
霍尔丹的筛子假设，大多数有助于适应的有益突变应该是占主导地位的，因为这些突变在罕见时最有可能建立和传播。然而，有人认为，如果突变在当前和以前的环境中的优势是相关的，霍尔丹筛子就可以被消除。我们构建了含有单一适应性突变的酿酒酵母杂合系，这些突变是在暴露于杀菌剂制霉菌素中获得的。在这里，我们发现在不同的环境中不存在明显的显性关系：突变在富培养基中表现出一系列的显性水平，而在制霉菌素胁迫下则是完全隐性的。令人惊讶的是，当暴露于制霉菌素时，杂合复制表现出可变的快速生长。靶向Sanger测序表明，杂合性缺失（LOH）解释了这些生长模式。我们的实验表明，隐性有益突变可以通过快速LOH在克隆生物中避免霍尔丹筛，从而有助于快速进化适应。
Haldane's sieve posits that the majority of beneficial mutations that contribute to adaptation should be dominant, as these are the mutations most likely to establish and spread when rare. It has been argued, however, that if the dominance of mutations in their current and previous environments are correlated, Haldane's sieve could be eliminated. We constructed heterozygous lines of Saccharomyces cerevisiae containing single adaptive mutations obtained during exposure to the fungicide nystatin. Here we show that no clear dominance relationship exists across environments: mutations exhibited a range of dominance levels in a rich medium, yet were exclusively recessive under nystatin stress. Surprisingly, heterozygous replicates exhibited variable-onset rapid growth when exposed to nystatin. Targeted Sanger sequencing demonstrated that loss-of-heterozygosity (LOH) accounted for these growth patterns. Our experiments demonstrate that recessive beneficial mutations can avoid Haldane's sieve in clonal organisms through rapid LOH and thus contribute to rapid evolutionary adaptation.