Mechanistic approaches to the study of evolution: the functional synthesis

Abstract
By combining evolutionary sequence analyses and manipulative molecular experiments, the functional synthesis of molecular evolution provides a powerful framework to elucidate the mechanisms by which historical mutations have altered biochemical processes and produced novel phenotypes. By using this approach, inferred ancestral sequences can be resurrected and their phenotypes and fitness effects assessed experimentally. The functional synthesis of molecular evolution provides independent corroboration of statistical inferences that have been drawn from sequence analyses. The functional synthesis of molecular evolution explicitly connects genotype with phenotype to allow mechanistic insights into the causes of adaptive change and evolutionary constraint. The functional synthesis of molecular evolution provides decisive tests of recent adaptations where genetic variation still segregates in present-day species, and of ancient adaptations where genetic variation is fixed in present-day species. The functional synthesis of molecular evolution can resolve long-standing questions about evolutionary processes and important evolutionary questions about metabolic, cellular, developmental and behavioural systems. The functional synthesis of molecular evolution can be used to characterize adaptive landscapes and explore the evolution of complexity. The functional synthesis of molecular evolution is poised to move beyond studies of single genes to allow the analysis of the evolution of pathways and networks that are made up of multiple genes. The functional synthesis of molecular evolution should become routine in studies of molecular evolution.