Gene birth contributes to structural disorder encoded by overlapping genes

S. Willis; J. Masel

The second hypothesis that we consider is that high ISD in overlapping genes is an artifact of the process of de novo gene birth [36] . There is no plausible path by which two non-overlapping genes could re-encode an equivalent protein sequence as overlapping; instead, an overlapping pair arises either when a second gene is born de novo within an existing gene, or when the boundaries of an existing gene are extended to create overlap [38] . In the latter case of "overprinting" [7] , [19] , [36] , the extended portion of that gene, if not the whole gene, is born de novo. One overlapping protein-coding sequence is therefore always evolutionarily younger than the other; we refer to these as "novel" versus "ancestral" overlapping genes or portions of genes. Genes may eventually lose their overlap through a process of gene duplication followed by subfunctionalization [19] , enriching overlapping genes for relatively young genes that have not yet been through this process. However, gene duplication may be inaccessible to many viruses (in particular, many RNA, ssDNA, and retroviruses), due to intrinsic geometric constraints on maximum nucleotide length [6] , [9] , [11] .