Complexities of recapitulating polygenic effects in natural populations: replication of genetic effects on wing shape in artificially selected and wild-caught populations of Drosophila melanogaster.
Complexities of recapitulating polygenic effects in natural populations: replication of genetic effects on wing shape in artificially selected and wild-caught populations of Drosophila melanogaster.
复制标题
重现自然种群多基因效应的复杂性：在人工选择和野生捕获的果蝇种群中复制遗传效应对翅膀形状的影响。
DOI：
10.1093/genetics/iyad050
复制
发表时间：
2023
期刊：
影响因子：
3.3
通讯作者：
Dworkin,Ian
中科院分区：
文献类型：
--
作者：
Pelletier,Katie;Pitchers,WilliamR;Mammel,Anna;Northrop-Albrecht,Emmalee;Márquez,EladioJ;Moscarella,RosaA;Houle,David;Dworkin,Ian
确定复杂性状的遗传结构对许多遗传学家来说很重要，包括那些对人类疾病，植物和动物育种以及进化遗传学感兴趣的人。全基因组关联研究的测序技术和统计方法的进步允许识别更多效应量较小的变异，然而，许多这些识别的多态性未能在后续研究中重复。除了抽样变异，这种复制失败反映了环境变异、遗传背景和种群间等位基因频率差异等因素带来的复杂性。使用果蝇的翅膀形状，我们问我们是否可以复制多态性的等位基因效应，首先在全基因组关联研究中确定了三个基因：dachsous，extra-macrochaete和neuralized，在实验室中使用人工选择，并在自然群体中进行批量分离作图。我们证明，与这些基因相关的多变量翅形变化与自然种群中表型和遗传变异的主轴对齐。经过沿着达克斯形状变化载体的七代人工选择，我们观察到在河马信号传导途径中包含其他基因的变体indachsous和基因组区域的遗传分化。这表明，在一个发展网络中，有一个共同的效应方向。我们还用额外的巨毛类变形载体进行了人工选择，这不是河马信号网络的一部分，但显示出很大程度上共享的影响方向。对选择的反应沿着emc载体是类似的dachsous，表明一个群体的可用遗传多样性，概括的遗传（协）方差矩阵（G），影响等位基因的选择捕获。尽管人工选择取得了成功，但使用自然群体的批量分离分析没有检测到这些相同的变体，这可能是由于环境变化和低次要等位基因频率的贡献，加上贡献变体的小效应大小。
Identifying the genetic architecture of complex traits is important to many geneticists, including those interested in human disease, plant and animal breeding, and evolutionary genetics. Advances in sequencing technology and statistical methods for genome-wide association studies have allowed for the identification of more variants with smaller effect sizes, however, many of these identified polymorphisms fail to be replicated in subsequent studies. In addition to sampling variation, this failure to replicate reflects the complexities introduced by factors including environmental variation, genetic background, and differences in allele frequencies among populations. UsingDrosophila melanogasterwing shape, we ask if we can replicate allelic effects of polymorphisms first identified in a genome-wide association studies in three genes:dachsous,extra-macrochaete, andneuralized, using artificial selection in the lab, and bulk segregant mapping in natural populations. We demonstrate that multivariate wing shape changes associated with these genes are aligned with major axes of phenotypic and genetic variation in natural populations. Following seven generations of artificial selection along thedachsousshape change vector, we observe genetic differentiation of variants indachsousand genomic regions containing other genes in the hippo signaling pathway. This suggests a shared direction of effects within a developmental network. We also performed artificial selection with theextra-macrochaeteshape change vector, which is not a part of the hippo signaling network, but showed a largely shared direction of effects. The response to selection along theemcvector was similar to that ofdachsous, suggesting that the available genetic diversity of a population, summarized by the genetic (co)variance matrix (G), influenced alleles captured by selection. Despite the success with artificial selection, bulk segregant analysis using natural populations did not detect these same variants, likely due to the contribution of environmental variation and low minor allele frequencies, coupled with small effect sizes of the contributing variants.