Renganaath Kaushik, Albert Frank W
Department of Genetics, Cell Biology, & Development, University of Minnesota, Minneapolis, MN 55455, USA.
bioRxiv. 2024 Jul 8:2023.11.14.567054. doi: 10.1101/2023.11.14.567054.
Regulatory genetic variation shapes gene expression, providing an important mechanism connecting DNA variation and complex traits. The causal relationships between gene expression and complex traits remain poorly understood. Here, we integrated transcriptomes and 46 genetically complex growth traits in a large cross between two strains of the yeast . We discovered thousands of genetic correlations between gene expression and growth, suggesting potential functional connections. Local regulatory variation was a minor source of these genetic correlations. Instead, genetic correlations tended to arise from multiple independent -acting regulatory loci. -acting hotspots that affect the expression of numerous genes accounted for particularly large fractions of genetic growth variation and of genetic correlations between gene expression and growth. Genes with genetic correlations were enriched for similar biological processes across traits, but with heterogeneous direction of effect. Our results reveal how -acting regulatory hotspots shape complex traits by altering cellular states.
调控基因变异塑造基因表达，提供了一种连接DNA变异与复杂性状的重要机制。基因表达与复杂性状之间的因果关系仍知之甚少。在此，我们在酵母两个菌株的一个大型杂交群体中整合了转录组和46个遗传复杂的生长性状。我们发现了基因表达与生长之间数千种遗传相关性，暗示了潜在的功能联系。局部调控变异是这些遗传相关性的一个次要来源。相反，遗传相关性倾向于源自多个独立作用的调控位点。影响众多基因表达的作用热点在遗传生长变异以及基因表达与生长之间的遗传相关性中占特别大的比例。具有遗传相关性的基因在不同性状间的相似生物学过程中富集，但效应方向各异。我们的结果揭示了作用调控热点如何通过改变细胞状态来塑造复杂性状。
