Center for Human Genetics, Marburg University, Marburg, 35043, Germany.
Institute for Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, 8057, Switzerland.
Nat Commun. 2024 Apr 18;15(1):3327. doi: 10.1038/s41467-024-46658-1.
Many organismal traits are genetically determined and covary in evolving populations. The resulting trait correlations can either help or hinder evolvability - the ability to bring forth new and adaptive phenotypes. The evolution of evolvability requires that trait correlations themselves must be able to evolve, but we know little about this ability. To learn more about it, we here study two evolvable systems, a yellow fluorescent protein and the antibiotic resistance protein VIM-2 metallo beta-lactamase. We consider two traits in the fluorescent protein, namely the ability to emit yellow and green light, and three traits in our enzyme, namely the resistance against ampicillin, cefotaxime, and meropenem. We show that correlations between these traits can evolve rapidly through both mutation and selection on short evolutionary time scales. In addition, we show that these correlations are driven by a protein's ability to fold, because single mutations that alter foldability can dramatically change trait correlations. Since foldability is important for most proteins and their traits, mutations affecting protein folding may alter trait correlations mediated by many other proteins. Thus, mutations that affect protein foldability may also help shape the correlations of complex traits that are affected by hundreds of proteins.
许多生物特征是由基因决定的，并在进化种群中共同演变。由此产生的特征相关性可能有助于或阻碍可进化性——即产生新的适应表型的能力。可进化性的进化要求特征相关性本身必须能够进化，但我们对此知之甚少。为了更多地了解这一点，我们在这里研究了两个可进化系统，一种黄色荧光蛋白和抗生素耐药蛋白 VIM-2 金属β-内酰胺酶。我们考虑了荧光蛋白中的两个特征，即发出黄色和绿色光的能力，以及我们的酶中的三个特征，即对氨苄青霉素、头孢噻肟和美罗培南的耐药性。我们表明，通过短时间尺度上的突变和选择，这些特征之间的相关性可以迅速进化。此外，我们还表明，这些相关性是由蛋白质的折叠能力驱动的，因为改变折叠能力的单一突变可以显著改变特征相关性。由于折叠能力对大多数蛋白质及其特征很重要，因此影响蛋白质折叠的突变可能会改变由许多其他蛋白质介导的特征相关性。因此，影响蛋白质折叠能力的突变也可能有助于塑造受数百种蛋白质影响的复杂特征的相关性。
