Gene Birth Contributes to Structural Disorder Encoded by Overlapping Genes.
The same nucleotide sequence can encode two protein products in different reading frames. Overlapping gene regions encode higher levels of intrinsic structural disorder (ISD) than nonoverlapping genes (39% vs. 25% in our viral dataset). This might be because of the intrinsic properties of the genetic code, because one member per pair was recently born de novo in a process that favors high ISD, or because high ISD relieves increased evolutionary constraint imposed by dual-coding. Here, we quantify the relative contributions of these three alternative hypotheses. We estimate that the recency of de novo gene birth explains [Formula: see text] or more of the elevation in ISD in overlapping regions of viral genes. While the two reading frames within a same-strand overlapping gene pair have markedly different ISD tendencies that must be controlled for, their effects cancel out to make no net contribution to ISD. The remaining elevation of ISD in the older members of overlapping gene pairs, presumed due to the need to alleviate evolutionary constraint, was already present prior to the origin of the overlap. Same-strand overlapping gene birth events can occur in two different frames, favoring high ISD either in the ancestral gene or in the novel gene; surprisingly, most de novo gene birth events contained completely within the body of an ancestral gene favor high ISD in the ancestral gene (23 phylogenetically independent events vs. 1). This can be explained by mutation bias favoring the frame with more start codons and fewer stop codons.
['Willis|Sara|S|0000-0002-1605-6426', 'Masel|Joanna|J|0000-0002-7398-2127']
D001483:Base Sequence D005075:Biological Evolution D003062:Codon D030541:Databases, Genetic D019143:Evolution, Molecular D005807:Genes, Overlapping D005814:Genes, Viral D014644:Genetic Variation D006801:Humans D064267:Intrinsically Disordered Proteins D059645:Mutation Rate D016366:Open Reading Frames D010802:Phylogeny D011506:Proteins D016364:Reading Frames D012689:Sequence Homology, Nucleic Acid
evolutionary constraint alternative reading frame gene age mutation-driven evolution overprinting