Retooling spare parts: gene duplication and cognition

Abstract

Two new studies experimentally demonstrate how ancient genomic duplications of synaptic genes provided the substrate for diversification that ultimately expanded vertebrate cognitive complexity.

Figure 1. How drift and selection can result in functional diversification

Nithianantharajah and colleagues found functional diversification among the four Dlg paralogs in vertebrates and compared this function to the known function of the single invertebrate dlg. Here we present a hypothetical scenario of how such genes could diverge following the two rounds of genome duplication. As the ancestral gene had a critical function, purifying selection continues to act on the invertebrate gene, keeping the population frequency of deleterious mutations low. A drifting mutation, coupled with a change in environment, gives this gene a new, added function, after which it continues to operate under purifying selection. Dlg1 has some new, nonfunctional mutations fixed owing to genetic drift, and is only acted on by purifying selection when the other three paralogous genes have lost their core ancestral function. Dlg4 undergoes two periods in which beneficial mutations are positively selected to fixation, separated by an epoch of purifying selection on the first newly derived function. The gene loses its core ancestral function through genetic drift of a deleterious mutation. Dlg2 loses its ancestral function and gains new mutations by genetic drift until a beneficial gain-of-function mutation rapidly sweeps to fixation, at which point the gene is acted on by purifying selection for its new function. Dlg3 has multiple mutations fixed owing to drift and one beneficial mutation conferring a new function swept to fixation. After 550 million years of evolution, these genes have diversified, diverging from one another both in sequence and in function.