Diversification of the insulin-like growth factor 1 gene in mammals

Peter Rotwein,Josep V Planas

doi:10.1371/journal.pone.0189642

Abstract

Insulin-like growth factor 1 (IGF1), a small, secreted peptide growth factor, is involved in a variety of physiological and patho-physiological processes, including somatic growth, tissue repair, and metabolism of carbohydrates, proteins, and lipids. IGF1 gene expression appears to be controlled by several different signaling cascades in the few species in which it has been evaluated, with growth hormone playing a major role by activating a pathway involving the Stat5b transcription factor. Here, genes encoding IGF1 have been evaluated in 25 different mammalian species representing 15 different orders and ranging over ~180 million years of evolutionary diversification. Parts of the IGF1 gene have been fairly well conserved. Like rat Igf1 and human IGF1, 21 of 23 other genes are composed of 6 exons and 5 introns, and all 23 also contain recognizable tandem promoters, each with a unique leader exon. Exon and intron lengths are similar in most species, and DNA sequence conservation is moderately high in orthologous exons and proximal promoter regions. In contrast, putative growth hormone-activated Stat5b-binding enhancers found in analogous locations in rodent Igf1 and in human IGF1 loci, have undergone substantial variation in other mammals, and a processed retro-transposed IGF1 pseudogene is found in the sloth locus, but not in other mammalian genomes. Taken together, the fairly high level of organizational and nucleotide sequence similarity in the IGF1 gene among these 25 species supports the contention that some common regulatory pathways had existed prior to the beginning of mammalian speciation.

Highlights

Insulin-like growth factor 1 (IGF1) is a 70-residue, secreted protein that along with IGF2 and insulin comprises a conserved protein family found in most mammalian species and in many other vertebrates [1,2,3,4]
An iterative strategy was developed, in which homology searches first were conducted with segments of the rat Igf1 gene, followed by secondary searches using either components of human IGF1 or other genes that were evolutionarily more similar to specific target species, with a final follow-up using the resources of the SRA NCBI to identify IGF1 gene segments not detected in Ensembl
This report focuses on the molecular genetics of IGF1, as seen through the lens of 25 mammalian species

Summary

Introduction

Insulin-like growth factor 1 (IGF1) is a 70-residue, secreted protein that along with IGF2 and insulin comprises a conserved protein family found in most mammalian species and in many other vertebrates [1,2,3,4]. Two gene promoters have been shown to control IGF1 gene expression in the few mammals in which it has been studied experimentally, [2, 15,16,17,18,19,20].

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Conclusion