Dynamics of regulatory evolution in primate beta-globin gene clusters: cis-mediated acquisition of simian gamma fetal...

Phylogenetic reconstructions by parsimony were carried out on an enlarged body of primate gamma1 and gamma2-globin sequences. The results confirm that gamma1 and gamma2 arose from a tandem duplication in an ancient simian lineage ancestral to both platyrrhines (New World monkeys) and catarrhines (Old World monkeys and hominoids). Gene conversions between the two gamma homologs were frequent over the gamma gene proper but less frequent over the 5' flanking and very infrequent over the 3' flanking regions. The ancient platyrrhine conversion in the most distal 5' flanking region had the polarity of gamma2-->gamma1. Recent platyrrhine conversions between 5' regulatory sequences were very infrequent, in striking contrast to catarrhines which have large, uninterrupted stretches of converted 5' regulatory sequences. Comparisons of reconstructed ancestral primate and simian gamma promoter sequences revealed an accumulation of 21 nucleotide substitutions concentrated in or near cis-elements that may have mediated the change from embryonic to fetal gamma expression. Almost all 21 substitutions were retained in the lineages leading to functional gamma genes of extant catarrhines (both gamma1 and gamma2) and platyrrhines (most often gamma2). Fewer of these simian specific substitutions were retained in the platyrrhine gamma1 genes and new mutations occurred more often in the platyrrhine gamma1 than gamma2 promoters.