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多基因性和上位性是多亲本实验进化(CeMEE)面板中与适应度相关性状的基础。

Polygenicity and Epistasis Underlie Fitness-Proximal Traits in the Multiparental Experimental Evolution (CeMEE) Panel.

机构信息

Center for Genomics and Systems Biology, Department of Biology, New York University, New York 10003

Instituto Gulbenkian de Ciência, P-2781-901 Oeiras, Portugal.

出版信息

Genetics. 2017 Dec;207(4):1663-1685. doi: 10.1534/genetics.117.300406. Epub 2017 Oct 24.

Abstract

Understanding the genetic basis of complex traits remains a major challenge in biology. Polygenicity, phenotypic plasticity, and epistasis contribute to phenotypic variance in ways that are rarely clear. This uncertainty can be problematic for estimating heritability, for predicting individual phenotypes from genomic data, and for parameterizing models of phenotypic evolution. Here, we report an advanced recombinant inbred line (RIL) quantitative trait locus mapping panel for the hermaphroditic nematode , the multiparental experimental evolution (CeMEE) panel. The CeMEE panel, comprising 507 RILs at present, was created by hybridization of 16 wild isolates, experimental evolution for 140-190 generations, and inbreeding by selfing for 13-16 generations. The panel contains 22% of single-nucleotide polymorphisms known to segregate in natural populations, and complements existing mapping resources by providing fine resolution and high nucleotide diversity across > 95% of the genome. We apply it to study the genetic basis of two fitness components, fertility and hermaphrodite body size at time of reproduction, with high broad-sense heritability in the CeMEE. While simulations show that we should detect common alleles with additive effects as small as 5%, at gene-level resolution, the genetic architectures of these traits do not feature such alleles. We instead find that a significant fraction of trait variance, approaching 40% for fertility, can be explained by sign epistasis with main effects below the detection limit. In congruence, phenotype prediction from genomic similarity, while generally poor ([Formula: see text]), requires modeling epistasis for optimal accuracy, with most variance attributed to the rapidly evolving chromosome arms.

摘要

理解复杂性状的遗传基础仍然是生物学中的一个主要挑战。多基因性、表型可塑性和上位性以很少明确的方式导致表型方差。这种不确定性对于估计遗传力、从基因组数据预测个体表型以及参数化表型进化模型都是有问题的。在这里,我们报告了一个用于雌雄同体线虫的先进重组近交系(RIL)数量性状位点作图面板,即多亲本实验进化(CeMEE)面板。CeMEE 面板目前由 507 个 RIL 组成,是通过 16 个野生分离株的杂交、140-190 代的实验进化以及 13-16 代的自交产生的。该面板包含了在自然种群中分离的 22%的单核苷酸多态性,通过在>95%的基因组上提供精细分辨率和高核苷酸多样性,补充了现有的作图资源。我们将其应用于研究两个适合度成分的遗传基础,即繁殖力和繁殖时的雌雄同体体型,在 CeMEE 中具有高的广义遗传力。虽然模拟表明我们应该能够检测到加性效应小至 5%的常见等位基因,但在基因水平分辨率下,这些性状的遗传结构并不具有这样的等位基因。相反,我们发现,大量的性状方差(对于繁殖力来说,接近 40%)可以通过主要效应低于检测限的符号上位性来解释。一致地,从基因组相似性预测表型,虽然一般较差([公式:见文本]),但需要建模上位性以获得最佳准确性,其中大部分方差归因于快速进化的染色体臂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fce1/5714472/42e5ca41aa2c/1663fig1.jpg

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