Dibyachintan Soham, Dube Alexandre K, Bradley David, Lemieux Pascale, Dionne Ugo, Landry Christian R
PROTEO-Regroupement Québécois de Recherche sur la Fonction, l'Ingénierie et les Applications des Protéines, Québec, QC, Canada.
Centre de Recherche en Données Massives de l'Université Laval, Université Laval, Québec, QC, Canada.
bioRxiv. 2024 Mar 26:2024.02.23.581840. doi: 10.1101/2024.02.23.581840.
Paralogous genes are often redundant for long periods of time before they diverge in function. While their functions are preserved, paralogous proteins can accumulate mutations that, through epistasis, could impact their fate in the future. By quantifying the impact of all single-amino acid substitutions on the binding of two myosin proteins to their interaction partners, we find that the future evolution of these proteins is highly contingent on their regulatory divergence and the mutations that have silently accumulated in their protein binding domains. Differences in the promoter strength of the two paralogs amplify the impact of mutations on binding in the lowly expressed one. While some mutations would be sufficient to non-functionalize one paralog, they would have minimal impact on the other. Our results reveal how functionally equivalent protein domains could be destined to specific fates by regulatory and cryptic coding sequence changes that currently have little to no functional impact.
旁系同源基因在功能发生分化之前，通常会在很长一段时间内保持冗余状态。在其功能得以保留的同时，旁系同源蛋白可能会积累突变，而这些突变通过上位性作用，可能会影响它们未来的命运。通过量化所有单氨基酸替换对两种肌球蛋白与其相互作用伙伴结合的影响，我们发现这些蛋白质的未来进化在很大程度上取决于它们的调控分化以及在其蛋白质结合结构域中悄然积累的突变。两种旁系同源物启动子强度的差异会放大突变对低表达旁系同源物结合的影响。虽然某些突变足以使一个旁系同源物失去功能，但对另一个旁系同源物的影响却微乎其微。我们的研究结果揭示了功能等效的蛋白质结构域如何通过目前几乎没有功能影响的调控和隐秘编码序列变化，走向特定的命运。
