Lynch Michael, Hagner Kyle
Departments of Biology and
Physics, Indiana University, Bloomington, IN 47401.
Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):E30-8. doi: 10.1073/pnas.1421641112. Epub 2014 Dec 22.
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.
许多细胞功能依赖于高度特异性的分子间相互作用，例如转录因子及其DNA结合位点、微小RNA及其RNA结合位点、异二聚体蛋白质分子之间的界面、RNA分子中的茎，以及信号转导系统中的激酶及其应答调节因子。尽管相互作用的伙伴之间需要互补性，但即使在受到强烈选择的情况下，这种成对系统似乎也能够发生高度的进化分歧。这种行为是由于伙伴之间增加结合亲和力的优势逐渐减少、选择性等效替代方案之间进化途径的多样性以及进化过程的随机性所致。由于降低亲和力的突变压力与增强相互作用的选择压力相互冲突，即使面对恒定的选择，相互作用伙伴之间匹配程度的预期分布也可能出现双峰情况。尽管具有更多相互作用伙伴的生物分子进化保守性水平会提高，但它们更多的伙伴并不一定收敛于单个序列基序，也不一定在更复杂的系统中受到越来越多的限制。这些结果表明，结合界面序列中的大多数系统发育差异不是适应性微调的结果，而是随机遗传漂变的简单后果。
