Gene birth contributes to structural disorder encoded by overlapping genes

S. Willis; J. Masel

Under the constraint hypothesis, ancestral overlapping proteins will still have elevated ISD relative to non-overlapping proteins, even if it is less elevated than that of novel overlapping proteins. Elevated ISD in the ancestral member of the gene pair might have already been there at the moment of gene birth, or it might have subsequently evolved, representing two subhypotheses within the overall hypothesis of constraint. The overlapping gene pairs that we observe are those that have been retained; if either member of the overlapping pair was born with low ISD, then constraint makes it difficult to adapt to a changing environment, and that pair is less likely to be retained. When the ancestral member of the pair already has high ISD at the moment at which the novel gene is functionalized, long-term maintenance of both genes in the face of constraint is more likely. The "already there" or "preadaptation" [52] version of the constraint hypothesis predicts that the pre-overlapping ancestors of today's ancestral overlapping genes had higher ISD than other genes, perhaps because these gene pairs are the ones to have been retained. While these ancestral sequences are not available, as a proxy we use homologous sequences from basal lineages whose most recent common ancestry predates the origin of the overlap. For simplicity, we refer to these sequences as "pre-overlapping" to distinguish them from "non-overlapping" genes never known to have overlap. The preadaptation version of the constraint hypothesis predicts higher ISD in pre-overlapping genes than in non-overlapping genes.