Nucleotide sequence analysis of the lemur beta-globin gene family: evidence for major rate fluctuations in globin polypeptide evolution

Lemur beta-related globin genes have been isolated and sequenced. Orthologyof prosimian and human epsilon-, gamma-, and beta-related globin genes wasestablished by dot-matrix analysis. All of these lemur globin genespotentially encode functional beta-related globin polypeptides, thoughprecisely when the gamma-globin gene is expressed remains unknown. Theorganization of the 18-kb brown lemur beta-globin gene cluster (5'epsilon-gamma-[psi eta-delta]-beta 3') is consistent with its evolution bycontraction via unequal crossing-over from the putative ancestral mammalianbeta-globin gene cluster (5' epsilon-gamma- eta-delta-beta 3'). The dwarflemur nonadult globin genes are arranged as in the brown lemur. Similarlevels of synonymous (silent) nucleotide substitutions and noncoding DNAsequence differences have accumulated between species in all of thesegenes, suggesting a uniform rate of noncoding DNA divergence throughoutprimate beta-globin gene clusters. These differences are comparable withthose observed in the nonfunctional psi eta pseudogene and have thereforeaccumulated at the presumably maximal neutral rate. In contrast,nonsynonymous (replacement) nucleotide substitutions show a significantheterogeneity in distribution for both the same gene in different lineagesand different genes in the same lineage. These major fluctuations inreplacement but not silent substitution rates cannot be attributed tochanges in mutation rate, suggesting that changes in the rate of globinpolypeptide evolution in primates is not governed solely by variablemutation rates.