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

The process of gene birth is of major interest with current excitement concerning de novo gene formation. We report a new and different mechanism of de novo gene birth based on the finding and the characteristics of a short non-coding sequence situated between two protein genes, termed a spacer sequence. This non-coding sequence is present in genomes of Mus musculus, the house mouse and Philippine tarsier, a primitive ancestral primate. The ancestral sequence is highly conserved during primate evolution with certain base pairs totally invariant from mouse to humans. By following the birth of the sequence of human lincRNA BCRP3 (BCR activator of RhoGEF and GTPase 3 pseudogene) during primate evolution, we find diverse genes, long non-coding RNA and protein genes (and sequences that do not appear to encode a gene) that all stem from the 3' end of the spacer, and all begin with a similar sequence. During primate evolution, part of the BCRP3 sequence initially formed in the Old World Monkeys and developed into different primate genes before evolving into the BCRP3 gene in humans. The gene developmental process consists of the initiation of DNA synthesis at spacer 3' ends, addition of a complex of tandem transposable elements and the addition of a segment of another gene. The findings support the concept of the spacer sequence as a starting site for DNA synthesis that leads to formation of different genes with the addition of other sequences. These data suggest a new process of de novo gene birth.