Modeling Length Changes in De Novo Open Reading Frames during Neutral Evolution

Abstract

Abstract For protein coding genes to emerge de novo from a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newborn de novo gene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that older de novo genes have longer ORF, but it is not clear if they elongated with time or remained of the same length since their inception. To address this question we developed a mathematical model of ORF elongation as a Markov-jump process, and show that ORFs tend to keep their length in short evolutionary timescales. We also show that if change occurs it is likely to be a truncation. Our genomics and transcriptomics data analyses of seven Drosophila melanogaster populations are also in agreement with the model’s prediction. We conclude that selection could facilitate ORF length extension that may explain why longer ORFs were observed in old de novo genes in studies analysing longer evolutionary time scales. Alternatively, shorter ORFs may be purged because they may be less likely to yield functional proteins.