Department of Molecular Biology, Max Planck Institute for Developmental Biology, 72076, Tübingen, Germany.
Department of Plant Sciences, University of California Davis, Davis, CA, 95616, USA.
Heredity (Edinb). 2021 Mar;126(3):383-395. doi: 10.1038/s41437-021-00403-2. Epub 2021 Feb 11.
Discoveries of adaptive gene knockouts and widespread losses of complete genes have in recent years led to a major rethink of the early view that loss-of-function alleles are almost always deleterious. Today, surveys of population genomic diversity are revealing extensive loss-of-function and gene content variation, yet the adaptive significance of much of this variation remains unknown. Here we examine the evolutionary dynamics of adaptive loss of function through the lens of population genomics and consider the challenges and opportunities of studying adaptive loss-of-function alleles using population genetics models. We discuss how the theoretically expected existence of allelic heterogeneity, defined as multiple functionally analogous mutations at the same locus, has proven consistent with empirical evidence and why this impedes both the detection of selection and causal relationships with phenotypes. We then review technical progress towards new functionally explicit population genomic tools and genotype-phenotype methods to overcome these limitations. More broadly, we discuss how the challenges of studying adaptive loss of function highlight the value of classifying genomic variation in a way consistent with the functional concept of an allele from classical population genetics.
近年来，适应性基因敲除和广泛的完整基因缺失的发现，促使人们对早期认为失活等位基因几乎总是有害的观点进行了重大反思。如今，对群体基因组多样性的调查揭示了广泛的功能丧失和基因含量变异，但这种变异的许多适应性意义仍然未知。在这里，我们通过群体基因组学的视角来研究适应性功能丧失的进化动态，并考虑使用群体遗传学模型来研究适应性失活等位基因的挑战和机遇。我们讨论了理论上预期的等位基因异质性的存在，即同一基因座上存在多个功能类似的突变，这如何与经验证据一致，以及为什么这会阻碍对选择的检测和与表型的因果关系。然后，我们回顾了在新的功能明确的群体基因组工具和基因型-表型方法方面取得的技术进展，以克服这些限制。更广泛地说，我们讨论了研究适应性功能丧失的挑战如何突出了以与经典群体遗传学中等位基因的功能概念一致的方式对基因组变异进行分类的价值。
