Variation in the Insulin-Like Growth Factor 1 Gene in Primates.

Abstract

Insulin-like growth factor 1 (IGF1) is a multifunctional peptide that is involved in a wide range of physiological and pathophysiological processes in many animal species, ranging from somatic growth in children to metabolism and tissue regeneration and repair in adults. The IGF1 gene is under multifactorial regulation in the few species in which it has been studied, with major control being exerted by growth hormone through a gene expression pathway involving inducible binding of the STAT5b transcription factor to dispersed enhancer elements. In this study, using resources available in public genomic databases, genes encoding IGF1 have been analyzed in a cohort of six nonhuman primate species representing >60 million years of evolutionary diversification from a common ancestor: chimpanzee, gorilla, macaque, olive baboon, marmoset, and mouse lemur. The IGF1 gene has been well conserved among these primates. Similar to human IGF1, each gene appears to be composed of six exons and five introns, and contains recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are very similar, and DNA sequence conservation is high, not only in orthologous exons and promoter regions, but also in putative growth hormone-activated STAT5b-binding enhancers that are found in analogous locations in IGF1 intron 3 and in 5' distal intergenic DNA. Taken together, the high level of organizational and nucleotide sequence similarity in the IGF1 gene and locus among these seven species supports the contention that common regulatory paradigms had existed prior to the onset of primate speciation >85 million years ago.