Parallel Selection Mapping Using Artificially Selected Mice Reveals Body Weight Control Loci
Parallel Selection Mapping Using Artificially Selected Mice Reveals Body Weight Control Loci
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DOI：
10.1016/j.cub.2012.03.011
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发表时间：
2012-05-08
期刊：
影响因子：
9.2
通讯作者：
Tautz, Diethard
中科院分区：
文献类型：
--
作者：
Chan, Yingguang Frank;Jones, Felicity C.;Tautz, Diethard
理解多基因性状如何在选择下进化是一个未解决的问题[1]，因为识别复杂性状的基因和理解多位点选择如何在基因组中运作存在挑战。在这里，我们研究多基因选择反应，使用人工选择实验。对来自7个独立的极端小鼠体重长期选择实验的近交品系（“高”品系重42-77 g，而“对照”品系重16-40 g）[2]在527，572个SNP处进行基因分型，以鉴定控制体重的基因座。我们确定了67个平行选择区域（PSR），其中高线共享在对照中很少发现的变体。通过比较一个选择实验[2-4]中的等位基因频率与其随机对照，我们发现经典的选择扫描集中在PSR上。“我们提出的证据支持两个G蛋白偶联受体GPR 133和PrIhras位置候选人控制体重。人工选择可能会模仿自然选择在野外：与控制基因座相比，我们发现减少杂合性的PSR异常大的野生小鼠在岛屿上。许多PSR与人类身高变异相关的基因座重叠[5]，可能是通过进化保守的功能途径。我们的数据表明，对复杂性状的平行选择可能会在参与不同但相关途径的许多基因上引起平行反应。
Understanding how polygenic traits evolve under selection is an unsolved problem [1], because challenges exist for identifying genes underlying a complex trait and understanding how multilocus selection operates in the genome. Here we study polygenic response to selection using artificial selection experiments. Inbred strains from seven independent long-term selection experiments for extreme mouse body weight ("high" lines weigh 42-77 g versus 16-40 g in "control" lines) [2] were genotyped at 527,572 SNPs to identify loci controlling body weight. We identified 67 parallel selected regions (PSRs) where high lines share variants rarely found among the controls. By comparing allele frequencies in one selection experiment [2-4] against its unselected control, we found classical selective sweeps centered on the PSRs." We present evidence supporting two G protein-coupled receptors GPR133 and PrIhras positional candidates controlling body weight. Artificial selection may mimic natural selection in the wild: compared to control loci, we detected reduced heterozygosity in PSRs in unusually large wild mice on islands. Many PSRs overlap loci associated with human height variation [5], possibly through evolutionary conserved functional pathways. Our data suggest that parallel selection on complex traits may evoke parallel responses at many genes involved in diverse but relevant pathways.