An ancestral genomic sequence that serves as a nucleation site for de novo gene birth

Abstract

A short non-coding sequence present between the gamma-glutamyltransferase 1 (GGT1) and gamma-glutamyltransferase 5 (GGT5) genes, termed a spacer sequence has been detected in the genomes of Mus musculus, the house mouse and in Philippine tarsier, a primitive ancestral primate. It is highly conserved during primate evolution with certain sequences being totally invariant from mouse to humans. Evidence is presented to show this intergenic sequence serves as a nucleation site for the initiation of diverse genes. We also outline the birth of the human lincRNA gene BCRP3 (BCR activator of RhoGEF and GTPase 3 pseudogene) during primate evolution. The gene developmental process involves sequence initiation, addition of a complex of tandem transposable elements and addition of a segment of another gene. The sequence, initially formed in the Old World Monkeys such as the Rhesus monkey (Macaca mulatta) and the baboon (Papio anubis), develops into different primate genes before evolving into the human BCRP3 gene; it appears to also include trial and error during sequence/gene formation. The protein gene, GGT5 may have also formed by spacer sequence initiation in an ancient ancestor such as zebrafish, but spacer and GGT5 gene sequence drift during evolution produced a divergence that precludes further assessment. Author summaryFor a number of decades researchers have been interested in how genes evolve and a number of mechanisms of gene formation have been defined. This manuscript describes a different process of gene formation, that of a small DNA sequence that does not code for a gene but serves as a nucleation site for the initiation of de novo gene formation. This non-coding DNA sequence appears to have been in existence for about hundred million years or more and has formed the basis for the birth of diverse genes during evolution of the primates. The questions of how and why new genes are born are important in terms of revealing how organisms, especially primates, progress to greater complexity during evolution; the question of "how" is particularly relevant to the creation of biological information ab initio during prebiotic and early cellular evolution.