遗传多态性在芽殖酵母跨代遗传中的作用
Role of genetic polymorphisms in transgenerational inheritance in budding yeast
摘要：
一个性状的跨代遗传可能受到遗传和环境因素的影响，但仍然知之甚少。我们研究了遗传多态性对酵母分离子跨代遗传的影响，这些分离子来自酿酒酵母实验室菌株和野生菌株之间的杂交。对于所分析的每个SNP，存在于少于一半的分离子组中的亲本等位基因被称为次要等位基因（MA）。我们发现了一个非随机分布的MA在隔离，表明自然选择。我们比较了隔离与高MA含量（MAC）相对于那些少，发现一个更显着的缩短滞后期长度为高MAC组响应于14天的乙醇训练。此外，对于高MAC组，在无乙醇培养基中恢复7天后，通过乙醇训练获得和表观遗传记忆的短滞后期更显著地丧失。氯化钠处理产生了类似的观察结果。使用公共数据集，我们发现MAC与数百个基因的mRNA表达有关。最后，我们发现MAC对已知加性数量性状基因座（QTL）数目高的性状有优先效应。这些结果为大多数MAs的轻微有害性质以及在具有较大MAC的个体或细胞中维持性状遗传的较低能力提供了证据，这对疾病预防和治疗以及复杂性状和疾病中的“缺失遗传性”问题具有影响。
英文摘要：
Transgenerational inheritance of a trait is presumably affected by both genetic and environmental factors but remains poorly understood. We studied the effect of genetic polymorphisms on transgenerational inheritance of yeast segregants that were derived from a cross between a laboratory strain and a wild strain of Saccharomyces cerevisiae. For each SNP analyzed, the parental allele present in less than half of the segregants panel was called the minor allele (MA). We found a nonrandom distribution of MAs in the segregants, indicating natural selection. We compared segregants with high MA content (MAC) relative to those with less and found a more dramatic shortening of the lag phase length for the high MAC group in response to 14 days of ethanol training. Also, the short lag phase as acquired and epigenetically memorized by ethanol training was more dramatically lost after 7 days of recovery in ethanol free medium for the high MAC group. Sodium chloride treatment produced similar observations. Using public datasets, we found MAC linkage to mRNA expression of hundreds of genes. Finally, we found preferential effect of MAC on traits with high number of known additive quantitative trait loci (QTLs). These results provide evidence for the slightly deleterious nature of most MAs and a lower capacity to maintain inheritance of traits in individuals or cells with greater MAC, which have implications for disease prevention and treatment and the "missing heritability" problem in complex traits and diseases.
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