Evolution of the proximal promoter region of the mammalian growth hormone gene

The evolutionary relationship between the proximal growth hormone (GH) gene promoter sequences of 12 mammalian species was explored by comparison of t heir trinucleotide composition and by multiple sequence alignment. Both app roaches yielded results that were consistent with the known fossil record-b ased phylogeny of the analysed sequences, suggesting that the two methods o f tree reconstruction might be equally efficient and reliable. The pattern of evolution inferred for the mammalian GH gene promoters was found to vary both temporally and spatially. Thus, two distinct regions devoid of any ev olutionary changes exist in primates, but only one of these 'gaps' is also observed in rodents, and neither is seen in ruminants. Furthermore, differe nt evolutionary rates must have prevailed during different periods of evolu tionary time and in different lineages, with a dramatic increase in evoluti onary rate apparent in primates. Since a similar pattern of discontinuity h as been previously noted for the evolution of the GH-coding regions, it may reflect the action of positive selection operating upon the GH gene as a s ingle cohesive unit. Strong evidence for the action of gene conversion betw een primate GH gene promoters is provided by the fact that the human GH1 an d GH2 sequences, which are thought to have diverged before the divergence o f Old World monkeys from great apes, are more similar to one another than e ither is to the rhesus monkey GH2 promoter. Finally, it was noted that a nu mber of nucleotide positions in the GH1 gene promoter that are polymorphic in humans appear to be highly conserved in mammals. This apparent conundrum , which could represent a caveat for the interpretation of phylogenetic foo tprinting studies, is potentially explicable in terms either of reduced gen etic diversity in highly inbred animal species or insufficient population d ata from nonhuman species. (C) 1999 Elsevier Science B.V. All rights reserv ed.