Frequent lineage-specific substitution rate changes support an episodic model for protein evolution

Abstract

AbstractSince the inception of the molecular clock model for sequence evolution, the investigation of protein divergence has revolved around the question of a more or less constant rate of overall sequence information change. Although anomalies in clock-like divergence are described for some proteins, nowadays, the assumption of a constant decay rate for a given protein family is taken as the null model for protein evolution. Still, so far, a systematic test of this null model has not been done at a genome-wide scale despite the databases’ enormous growth. We focus here on divergence rate comparisons between closely related lineages, since this allows clear orthology assignments by synteny and unequivocal alignments, which are crucial for the determination of substitution rate changes. Thus, we generated a high-confidence dataset of syntenic orthologs from four ape species, including humans. Further analysis revealed that despite the appearance of an overall clock-like substitution pattern, a substantial number of proteins show lineage-specific acceleration and deceleration in divergence rates, or combinations of both in different lineages. Interestingly, when aggregated, even the families showing large lineage-specific rate perturbations can show overall rate equality. Our analysis uncovers a much more dynamic history of substitution rate changes in protein families. Which invalidates a pan-genome null model of constant decay, on the one hand, but remains compatible with the existing notion that aggregated data can be reliably used to estimate species splitting time. Ultimately, our data shows that a null model of constant change is not suitable to predict the evolutionary trajectories of individual proteins.