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多细胞真菌中随机有益突变间的收益递减上位性

Diminishing-returns epistasis among random beneficial mutations in a multicellular fungus.

作者信息

Schoustra Sijmen, Hwang Sungmin, Krug Joachim, de Visser J Arjan G M

机构信息

Laboratory of Genetics, Wageningen University, Wageningen, The Netherlands

Institute of Theoretical Physics, University of Cologne, Cologne, Germany.

出版信息

Proc Biol Sci. 2016 Aug 31;283(1837). doi: 10.1098/rspb.2016.1376.

Abstract

Adaptive evolution ultimately is fuelled by mutations generating novel genetic variation. Non-additivity of fitness effects of mutations (called epistasis) may affect the dynamics and repeatability of adaptation. However, understanding the importance and implications of epistasis is hampered by the observation of substantial variation in patterns of epistasis across empirical studies. Interestingly, some recent studies report increasingly smaller benefits of beneficial mutations once genotypes become better adapted (called diminishing-returns epistasis) in unicellular microbes and single genes. Here, we use Fisher's geometric model (FGM) to generate analytical predictions about the relationship between the effect size of mutations and the extent of epistasis. We then test these predictions using the multicellular fungus Aspergillus nidulans by generating a collection of 108 strains in either a poor or a rich nutrient environment that each carry a beneficial mutation and constructing pairwise combinations using sexual crosses. Our results support the predictions from FGM and indicate negative epistasis among beneficial mutations in both environments, which scale with mutational effect size. Hence, our findings show the importance of diminishing-returns epistasis among beneficial mutations also for a multicellular organism, and suggest that this pattern reflects a generic constraint operating at diverse levels of biological organization.

摘要

适应性进化最终由产生新遗传变异的突变所推动。突变适应性效应的非加性(称为上位性)可能会影响适应的动态过程和可重复性。然而,由于实证研究中上位性模式存在显著差异,使得对上位性的重要性及影响的理解受到阻碍。有趣的是,最近一些研究报告称,在单细胞微生物和单个基因中,一旦基因型变得更好适应,有益突变的益处会越来越小(称为收益递减上位性)。在此,我们使用费希尔几何模型(FGM)来生成关于突变效应大小与上位性程度之间关系的分析预测。然后,我们通过在贫瘠或丰富营养环境中生成一组共108个携带有益突变的菌株,并利用有性杂交构建成对组合,使用多细胞真菌构巢曲霉来检验这些预测。我们的结果支持了FGM的预测,并表明在两种环境中有益突变之间均存在负上位性,且其与突变效应大小相关。因此,我们的研究结果表明收益递减上位性在有益突变中对于多细胞生物也很重要,并表明这种模式反映了在生物组织不同层面起作用的一种普遍限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d091/5013798/3c9fcaf4370d/rspb20161376-g1.jpg

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