DYNAMICS OF REGULATORY EVOLUTION IN PRIMATE BETA-GLOBIN GENE CLUSTERS- CIS-MEDIATED ACQUISITION OF SIMIAN GAMMA-FETAL EXPRESSION PATTERNS

Phylogenetic reconstructions by parsimony were carried out on an enlar ged body of primate gamma 1 and gamma 2-globin sequences. The results confirm that gamma 1 and gamma 2 arose from a tandem duplication in an ancient simian lineage ancestral to both platyrrhines (New World monk eys) and catarrhines (Old World monkeys and hominoids). Gene conversio ns between the two gamma homologs were frequent over the gamma gene pr oper but less frequent over the 5' flanking and very infrequent over t he 3' flanking regions. The ancient platyrrhine conversion in the most distal 5' flanking region had the polarity of gamma 2-->gamma 1. Rece nt platyrrhine conversions between 5' regulatory sequences were very i nfrequent, in striking contrast to catarrhines which have large, unint errupted stretches of converted 5' regulatory sequences. Comparisons o f reconstructed ancestral primate and simian gamma promoter sequences revealed an accumulation of 21 nucleotide substitutions concentrated i n or near cia-elements that may have mediated the change from embryoni c to fetal gamma expression. Almost all 21 substitutions were retained in the lineages leading to functional gamma genes of extant catarrhin es (both gamma 1 and gamma 2) and platyrrhines (most often gamma 2). F ewer of these simian specific substitutions were retained in the platy rrhine gamma 1 genes and new mutations occurred more often in the plat yrrhine gamma 1 than gamma 2 promoters. (C) 1997 Elsevier Science B.V.