期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：1
页码：E30-E38
DOI：10.1073/pnas.1421641112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMany cellular functions depend on highly specific intermolecular interactions, with mutational changes in each component of the interaction imposing coevolutionary pressure on the remaining members (e.g., a transcription factor and its DNA binding sites). The conflict between mutation pressure toward reduced affinity and selective pressure for greater interaction results in an evolutionary equilibrium distribution for the affinity between interacting partners. Nevertheless, conditional on the maintenance of a critical level of molecular recognition, the sites containing the key residues of binding interfaces are free to evolve. The theory developed suggests that most such evolution is a simple consequence of random genetic drift and not an outcome of adaptive fine tuning. Many cellular functions depend on highly specific intermolecular interactions, for example transcription factors and their DNA binding sites, microRNAs and their RNA binding sites, the interfaces between heterodimeric protein molecules, the stems in RNA molecules, and kinases and their response regulators in signal-transduction systems. Despite the need for complementarity between interacting partners, such pairwise systems seem to be capable of high levels of evolutionary divergence, even when subject to strong selection. Such behavior is a consequence of the diminishing advantages of increasing binding affinity between partners, the multiplicity of evolutionary pathways between selectively equivalent alternatives, and the stochastic nature of evolutionary processes. Because mutation pressure toward reduced affinity conflicts with selective pressure for greater interaction, situations can arise in which the expected distribution of the degree of matching between interacting partners is bimodal, even in the face of constant selection. Although biomolecules with larger numbers of interacting partners are subject to increased levels of evolutionary conservation, their more numerous partners need not converge on a single sequence motif or be increasingly constrained in more complex systems. These results suggest that most phylogenetic differences in the sequences of binding interfaces are not the result of adaptive fine tuning but a simple consequence of random genetic drift.
