Biology of Aging Doctoral Program, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089, USA.
Buck Institute for Research on Aging, Novato, CA, 94945, USA.
Heredity (Edinb). 2024 Nov;133(5):308-316. doi: 10.1038/s41437-024-00715-z. Epub 2024 Aug 20.
A key goal of evolutionary genomics is to harness molecular data to draw inferences about selective forces that have acted on genomes. The field progresses in large part through the development of advanced molecular-evolution analysis methods. Here we explored the intersection between classical sequence-based tests for selection and an empirical expression-based approach, using stem cells from Mus musculus subspecies as a model. Using a test of directional, cis-regulatory evolution across genes in pathways, we discovered a unique program of induction of translation genes in stem cells of the Southeast Asian mouse M. m. castaneus relative to its sister taxa. We then mined population-genomic sequences to pursue underlying regulatory mechanisms for this expression divergence, finding robust evidence for alleles unique to M. m. castaneus at the upstream regions of the translation genes. We interpret our data under a model of changes in lineage-specific pressures across Mus musculus in stem cells with high translational capacity. Our findings underscore the rigor of integrating expression and sequence-based methods to generate hypotheses about evolutionary events from long ago.
进化基因组学的一个主要目标是利用分子数据推断基因组所经历的选择压力。该领域的进展在很大程度上是通过开发先进的分子进化分析方法实现的。在这里，我们以 Mus musculus 亚种的干细胞为模型，探讨了经典的基于序列的选择测试与基于经验的表达方法之间的交叉点。我们使用一种跨基因途径的定向顺式调控进化的测试方法，发现了东南亚小鼠 M. m. castaneus 干细胞中翻译基因诱导的独特程序，与它的姐妹种相比。然后，我们挖掘了群体基因组序列，以寻找这种表达差异的潜在调控机制，在翻译基因的上游区域发现了 M. m. castaneus 特有的等位基因的有力证据。我们根据一个模型来解释我们的数据，该模型假设在具有高翻译能力的干细胞中，Mus musculus 谱系特异性压力发生了变化。我们的研究结果强调了整合表达和基于序列的方法的严谨性，以便从很久以前的进化事件中生成假说。
