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首页> 美国卫生研究院文献>PLoS Genetics >Evolution of Mutational Robustness in the Yeast Genome: A Link to Essential Genes and Meiotic Recombination Hotspots
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Evolution of Mutational Robustness in the Yeast Genome: A Link to Essential Genes and Meiotic Recombination Hotspots

机译：酵母基因组突变稳健性的演变：必需基因和减数分裂重组热点的链接。

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Deleterious mutations inevitably emerge in any evolutionary process and are speculated to decisively influence the structure of the genome. Meiosis, which is thought to play a major role in handling mutations on the population level, recombines chromosomes via non-randomly distributed hot spots for meiotic recombination. In many genomes, various types of genetic elements are distributed in patterns that are currently not well understood. In particular, important (essential) genes are arranged in clusters, which often cannot be explained by a functional relationship of the involved genes. Here we show by computer simulation that essential gene (EG) clustering provides a fitness benefit in handling deleterious mutations in sexual populations with variable levels of inbreeding and outbreeding. We find that recessive lethal mutations enforce a selective pressure towards clustered genome architectures. Our simulations correctly predict (i) the evolution of non-random distributions of meiotic crossovers, (ii) the genome-wide anti-correlation of meiotic crossovers and EG clustering, (iii) the evolution of EG enrichment in pericentromeric regions and (iv) the associated absence of meiotic crossovers (cold centromeres). Our results furthermore predict optimal crossover rates for yeast chromosomes, which match the experimentally determined rates. Using a Saccharomyces cerevisiae conditional mutator strain, we show that haploid lethal phenotypes result predominantly from mutation of single loci and generally do not impair mating, which leads to an accumulation of mutational load following meiosis and mating. We hypothesize that purging of deleterious mutations in essential genes constitutes an important factor driving meiotic crossover. Therefore, the increased robustness of populations to deleterious mutations, which arises from clustered genome architectures, may provide a significant selective force shaping crossover distribution. Our analysis reveals a new aspect of the evolution of genome architectures that complements insights about molecular constraints, such as the interference of pericentromeric crossovers with chromosome segregation.
机译：有害突变不可避免地出现在任何进化过程中，并被认为对基因组的结构具有决定性的影响。减数分裂被认为在处理群体水平的突变中起主要作用，它通过非随机分布的热点进行染色体重组以进行减数分裂重组。在许多基因组中，各种类型的遗传元件以目前尚不清楚的方式分布。特别地，重要的（必需的）基因成簇排列，这通常不能通过所涉及基因的功能关系来解释。在这里，我们通过计算机模拟显示，必需基因（EG）聚类在处理具有近交和近交水平可变的性人群中的有害突变方面提供了适应性好处。我们发现隐性致死突变对簇状基因组架构施加选择性压力。我们的模拟正确地预测了（i）减数分裂交换的非随机分布的演变，（ii）减数分裂交换和EG聚类的全基因组反相关性，（iii）着丝粒区域的EG富集的演化和（iv）相关的减数分裂交叉（冷着丝粒）的缺乏。我们的结果进一步预测了酵母染色体的最佳交叉速率，该速率与实验确定的速率相匹配。使用酿酒酵母条件突变体菌株，我们表明单倍体致死表型主要来自单个基因座的突变，通常不会损害交配，这导致减数分裂和交配后突变负荷的积累。我们假设清除必需基因中的有害突变是驱动减数分裂交叉的重要因素。因此，由簇状基因组结构引起的群体对有害突变的增强的鲁棒性可提供显着的选择性力塑造交叉分布。我们的分析揭示了基因组架构进化的一个新方面，该方面补充了对分子约束的见解，例如，围绕着着丝粒的交叉分子对染色体分离的干扰。

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