从大型遗传生物库中洞察人类进化
Insights into human evolution from large genetic biobanks
浏览论文内容
中文总结 AI 辅助
本文综述了利用大型遗传生物库在推断进化约束和关联自然选择与性状影响方面的最新进展，并讨论了其对理解遗传关联的意义及未来研究方向。
中文摘要 AI 辅助
具有深度表型分析和全外显子组或全基因组测序的大型遗传生物库的发展，正使我们对人类进化的理解日益深入。在此，我们回顾了两个主要研究方向的最新进展：1）利用不断增加的样本量来推断极强的进化约束；2）利用生物库广泛的表型分析，将自然选择对变异的影响与其对性状的影响联系起来。特别是，近年来在针对功能丧失突变的选择强度的基因特异性估计方面取得了进展，并且越来越多的证据支持多效性稳定选择对性状在塑造遗传多样性模式中的重要性。我们还讨论了这些发现如何反过来增进我们对生物库中发现的遗传关联的理解和解释。最后，我们概述了悬而未决的问题和未来研究的有前景的方向。
英文摘要
The development of large genetic biobanks with deep phenotyping and whole-exome or whole-genome sequencing is enabling an ever-deeper understanding of human evolution. Here we review recent developments in two main research directions: 1) using the increasing sample sizes to infer extremely strong evolutionary constraint and 2) leveraging biobanks' extensive phenotyping to relate the effects of natural selection on variants to their impacts on traits. In particular, there has been recent progress in gene-specific estimates of the strength of selection acting against loss-of-function mutations, as well as growing evidence supporting the importance of pleiotropic stabilizing selection on traits in shaping patterns of genetic diversity. We also discuss how these findings are, in turn, improving our understanding and interpretation of the genetic associations discovered in biobanks. Throughout, we outline open questions and promising directions for future research.
发表机构
- Institute for Human Genetics, University of California, San Francisco（加州大学旧金山分校人类遗传学研究所）
- Department of Epidemiology & Biostatistics, University of California, San Francisco（加州大学旧金山分校流行病学与生物统计系）
- Department of Data Science, University of Oregon（俄勒冈大学数据科学系）
- Institute for Ecology and Evolution, University of Oregon（俄勒冈大学生态与进化研究所）
机构由 AI 辅助整理，请以论文原文为准。
