Evolutionary meandering of intermolecular interactions along the drift barrier

Abstract

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 signaltransduction 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. cellular evolution | molecular interaction | transcription | random genetic drift | coevolution M uch of biology relies on the specificity of intermolecular interactions-the regulation of gene expression, the transmission of information via signal transduction, the assembly of monomeric subunits into multimers, vesicle sorting in eukaryotic cells, toxin-antitoxin systems in microbes, mating-type recognition, and many other cellular features. Although the basic structural features of such fitness-related traits would seem to be under strong purifying selection, molecular specificity often seems to be highly flexible in evolutionary time. For example, transcription-factor binding-site motifs often vary dramatically among orthologous genes in different species and even among similarly regulated genes within the same species (1-3). The binding interfaces of multimeric proteins can vary substantially among species, sometimes with no overlap at all (4, 5). The key amino acid sequences involved in intermolecular cross-talk in signal-transduction systems can evolve at high rates (6, 7), and growing evidence suggests that the locations of sites involved in posttranslational modification in individual proteins are under much weaker selective constraints than their absolute numbers (8). Although it is often argued that subtle differences in the motifs involved in intermolecular interactions are molded by the demands of natural selection, seldom has any direct evidence ever been provided in support of such arguments.The theory provided below makes the case...

The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division

“…The robustness of SPOR domains with respect to horizontal transfer is underscored by the ability of SPOR domains from B. subtilis, Cytophaga hutchinsonii, and Aquifex aeolicus to target septal PG in E. coli (11,13). In contrast, protein-protein interactions are mediated by molecular interfaces that are subject to rapid drift (53). As a consequence, a foreign division protein is unlikely to interact productively with its intended partner in the context of a new host.…”

How does epistasis influence the response to selection?

“…Kondrashov (1995) has made a related argument for the loss of fitness because of the random fixation of deleterious alleles for which N e s~1, and Lynch and Hagner (2015) have argued that adaptation is limited by the requirement that selection on each allele be stronger than drift (that is, N e s ≳1). However, Charlesworth (2013a, b), points out that these arguments do not apply to polygenic traits under stabilising selection: a trait can be kept near its optimum even when it depends on very many sites, such that the selection on each is much weaker than random drift.…”

“…The success of domestication shows that populations of just a few hundred can adapt well to radically new conditions (Hill and Kirkpatrick, 2010). However, over longer timescales, it would seem that a substantial and possibly catastrophic fitness decline must ensue, as random drift fixes slightly deleterious mutations (Kondrashov, 1995;Lynch and Hagner, 2015), and moves trait means away from their optima. Charlesworth (2013a) has criticised such arguments on the grounds that compensatory mutations prevent decline, and that stabilising selection can be effective even when individual alleles are dominated by drift.…”

Inferring the evolutionary mechanism of the chloroplast genome size by comparing whole-chloroplast genome sequences in seed plants

“…These associations were suggested to be determined by selective force 1, 3, 9 . Genome size change has also been linked to remarkable changes in non-coding sequences, and random drift is regarded as a strong evolutionary force that affects genome size variation 10, 11 . However, these associations between DNA composition and genome size 2, 9 have not been clarified in species over a broad range of evolutionary time.…”