Evolutionary formation of a human de novo open reading frame from a non-primate non-coding genomic region that proceeds via biased random mutations

Two open reading frames (ORFs) of evolutionary interest stem from the human gene SMIM45. An investigation shows that one consists of an ultra-conserved 68 amino acid (aa) sequence that dates back to the amphibians, [~]192 MYA. In contrast, the other, an ORF of 107 aa develops slowly during primate evolution. An early developmental stage of the 107 aa ORF has been detected in non-primate genomes. In the mouse, it consists of a small sequence homologous to a segment of the human 107 aa ORF, the aa sequence SGLE*VTVYGGGVQKGKT. This suggests the evolutionary root of the 107 aa ORF dates to an ancestor of the mouse; root species have been proposed based on the presence or absence of the early developmental sequence in ancestors. The formation of the complete 107 aa ORF during primate evolution is also outlined. Found is growth of the 107 aa ORF by biased random mutations. The delineation of mutations occurring during development of the 107 aa ORF can provide a model for the evolutionary formation of ORFs of de novo protein genes.