Exploring the Correlations Between Sequence Evolution Rate and Phenotypic Divergence Across the Mammalian Tree Provides Insights into Adaptive Evolution

Sequence evolution behaves in a relatively consistent manner, leading to one of the fundamental paradigms in biology, the existence of a 'molecular clock'. The molecular clock can be distilled to the concept of accumulation of substitutions, through time yielding a stable rate from which we can estimate lineage divergence. Over the last 50 years, evolutionary biologists have obtained an in-depth understanding of this clock's nuances. It has been fine-tuned by taking into account the vast heterogeneity in rates across lineages and genes, leading to 'relaxed' molecular clock methods for timetree reconstruction. Sequence rate varies with life history traits including body size, generation time and metabolic rate, and we review recent studies on this topic. However, few studies have explicitly examined correlates between molecular evolution and morphological evolution. The patterns observed across diverse lineages suggest that rates of molecular and morphological evolution are largely decoupled. We discuss how identifying the molecular mechanisms behind rapid functional radiations are central to understanding evolution. The vast functional divergence within mammalian lineages that have relatively 'slow' sequence evolution refutes the hypotheses that pulses in diversification yielding major phenotypic change are the result of steady accumulation of substitutions. Patterns rather suggest phenotypic divergence is likely caused by regulatory alterations mediated through mechanisms such as insertions/deletions in functional regions. These can rapidly arise and sweep to fixation faster than predicted from a lineage's sequence neutral substitution rate, enabling species to leapfrog between phenotypic 'islands'. We suggest research directions that could illuminate mechanisms behind the functional diversity we see today.