The early adaptive evolution of calmodulin

Interaction between gene duplication and natural selection in molecularevolution was investigated utilizing a phylogenetic tree constructed by theparsimony procedure from amino acid sequences of 50 calmodulin- familyprotein members. The 50 sequences, belonging to seven protein lineagesrelated by gene duplication (calmodulin itself, troponin-C, alkali andregulatory light chains of myosin, parvalbumin, intestinal calcium-bindingprotein, and glial S-100 phenylalanine-rich protein), came from a widerange of eukaryotic taxa and yielded a denser tree (more branch pointswithin each lineage) than in earlier studies. Evidence obtained from thereconstructed pattern of base substitutions and deletions in theseancestral loci suggests that, during the early history of the family,selection acted as a transforming force on expressed genes among theduplicates to encode molecular sites with new or modified functions. Inlater stages of descent, however, selection was a conserving force thatpreserved the structures of many coadapted functional sites. Each branch ofthe family was found to have a unique average tempo of evolutionary change,apparently regulated through functional constraints. Proteins whosefunctions dictate multiple interaction with several other macromoleculesevolved more slowly than those which display fewer protein-protein andprotein-ion interactions, e.g., calmodulin and next troponin-C evolved atthe slowest average rates, whereas parvalbumin evolved at the fastest. Thehistory of all lineages, however, appears to be characterized by rapidrates of evolutionary change in earlier periods, followed by slower ratesin more recent periods. A particularly sharp contrast between such fast andslow rates is found in the evolution of calmodulin, whose rate of change inearlier eukaryotes was manyfold faster than the average rate over the past1 billion years. In fact, the amino acid replacements in the nascentcalmodulin lineage occurred at residue positions that in extant metazoansare largely invariable, lending further support to the Darwinian hypothesisthat natural selection is both a creative and a conserving force inmolecular evolution.