Gene birth contributes to structural disorder encoded by overlapping genes

S. Willis; J. Masel

Finally, here we also consider the possibility that the high ISD observed in overlapping genes might simply be an artifact of the genetic code [21] . We perform for the first time the appropriate control, by predicting what the ISD would be if codons were read from alternative reading frames of existing non-overlapping genes. Any DNA sequence can be read in three reading frames on each of the two strands, for a total of 6 reading frames. We focus only on same-strand overlap, due to superior availability of reliable data on same-strand overlapping gene pairs. We classify the reading frame of each gene in an overlapping pair relative to its counterpart; if gene A is in the +1 frame with respect to gene B, this means that gene B is in the +2 frame with respect to gene A. We use the +0 frame designation just for nonoverlapping or pre-overlapping genes in their original frame. If the high ISD of overlapping genes is primarily driven by the intrinsic properties of the genetic code, then we expect their ISD values to closely match those expected from translation in the +1 vs. +2 frames of non-overlapping genes.