Irving-Pease Evan K, Muktupavela Rasa, Dannemann Michael, Racimo Fernando
Lundbeck Foundation GeoGenetics Centre, GLOBE Institute, University of Copenhagen, Copenhagen, Denmark.
Center for Genomics, Evolution and Medicine, Institute of Genomics, University of Tartu, Tartu, Estonia.
Front Genet. 2021 Aug 4;12:703541. doi: 10.3389/fgene.2021.703541. eCollection 2021.
Genetic association data from national biobanks and large-scale association studies have provided new prospects for understanding the genetic evolution of complex traits and diseases in humans. In turn, genomes from ancient human archaeological remains are now easier than ever to obtain, and provide a direct window into changes in frequencies of trait-associated alleles in the past. This has generated a new wave of studies aiming to analyse the genetic component of traits in historic and prehistoric times using ancient DNA, and to determine whether any such traits were subject to natural selection. In humans, however, issues about the portability and robustness of complex trait inference across different populations are particularly concerning when predictions are extended to individuals that died thousands of years ago, and for which little, if any, phenotypic validation is possible. In this review, we discuss the advantages of incorporating ancient genomes into studies of trait-associated variants, the need for models that can better accommodate ancient genomes into quantitative genetic frameworks, and the existing limits to inferences about complex trait evolution, particularly with respect to past populations.
来自国家生物样本库和大规模关联研究的基因关联数据为理解人类复杂性状和疾病的遗传进化提供了新的前景。反过来，现在从古代人类考古遗迹中获取基因组比以往任何时候都更容易，并且为了解过去性状相关等位基因频率的变化提供了一个直接窗口。这引发了新一轮的研究热潮，旨在利用古代DNA分析历史和史前时期性状的遗传成分，并确定这些性状是否经历了自然选择。然而，在人类中，当将预测扩展到数千年前死亡的个体，且几乎无法进行任何表型验证时，复杂性状推断在不同人群中的可转移性和稳健性问题尤其令人担忧。在这篇综述中，我们讨论了将古代基因组纳入性状相关变异研究的优势，需要能够更好地将古代基因组纳入数量遗传框架的模型，以及复杂性状进化推断的现有局限性，特别是关于过去人群的局限性。
