A THEORETICAL METHOD FOR EVALUATING THE RELATIVE IMPORTANCE OF POSITIVE SELECTION AND NEUTRAL DRIFT FROM OBSERVED BASE CHANGES

To evaluate the relative importance of positive selection and neutral drift from the nucleotide base changes observed in the homologous alig nment of genes, a theoretical equation of base changes is formulated b y including both the influence of selection and the base substitutions due to mutations. Under the assumption that the average rate of base substitutions estimated from synonymous changes is the ''true'' mutati on rate applicable at all positions, this method is applied to the ver tebrate globin gene family, and evaluates the departures of base chang e rates from the ''true'' mutation rate at the first and second codon positions as a consequence of preferential selection for the conservat ion of important function. In addition to the strong effect of selecti on on the amino acid residues in the internal region mostly common to myoglobin and hemoglobin chains, the distinctive directions of selecti ve parameter values are seen at sites on the globin surface, distingui shing the subunit contact residues of hemoglobins from the polar resid ues on the surface of myoglobins. Moreover, this effect of selection d istinguishing between the myoglobin and hemoglobin chain genes becomes weaker in cold-blooded vertebrates, especially in fish, strongly sugg esting the possibility that the clear distinction between these globin s is a result of selection out of the changes regarded as neutral ones in an ancestor of vertebrates. Thus, the present method may also serv e to investigate the homology of many other proteins from the aspect o f molecular evolution, mainly focusing on the evolution of their biolo gical functions.