Non-adaptive origins of interactome complexity

Abstract

Sampling bias in small populations can result in a non-adaptive evolutionary phenomenon called genetic drift. By comparing the protein-coding genomes of many species, Ariel Fernández and Michael Lynch show that population-size bottlenecks allow for the appearance of mildly destabilized proteins that can subsequently be re-stabilized through new protein–protein interactions. These interactions can then evolve into meaningful biochemical pathways. Thus, although complex protein architectures and interactions may be essential contributors to phenotypic complexity, such features may initially emerge through non-adaptive mechanisms. The boundaries between prokaryotes, unicellular eukaryotes and multicellular eukaryotes are accompanied by orders-of-magnitude reductions in effective population size, with concurrent amplifications of the effects of random genetic drift and mutation1. The resultant decline in the efficiency of selection seems to be sufficient to influence a wide range of attributes at the genomic level in a non-adaptive manner2. A key remaining question concerns the extent to which variation in the power of random genetic drift is capable of influencing phylogenetic diversity at the subcellular and cellular levels2,3,4. Should this be the case, population size would have to be considered as a potential determinant of the mechanistic pathways underlying long-term phenotypic evolution. Here we demonstrate a phylogenetically broad inverse relation between the power of drift and the structural integrity of protein subunits. This leads to the hypothesis that the accumulation of mildly deleterious mutations in populations of small size induces secondary selection for protein–protein interactions that stabilize key gene functions. By this means, the complex protein architectures and interactions essential to the genesis of phenotypic diversity may initially emerge by non-adaptive mechanisms.