De novoORFs are more likely to shrink than to elongate during neutral evolution

Abstract

For protein coding genes to emergede novofrom a non-genic DNA, the DNA sequence must gain an open reading frame (ORF) and the ability to be transcribed. The newbornde novogene can further evolve to accumulate changes in its sequence. Consequently, it can also elongate or shrink with time. Existing literature shows that olderde novogenes 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 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 sevenDrosophila melanogasterpopulations is 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 oldde novogenes in studies analysing longer evolutionary time scales.SignificanceNew protein coding genes can emerge from non-genic DNA through a process calledde novogene emergence. Genes thus emerged usually have a small open reading frame (ORF). However, studies show thatde novogenes with an older evolutionary origin have longer ORF than younger genes. To understand how ORF length evolves, we use a combination of mathematical modeling and population level genome data analysis. We find that in the absence of evolutionary selection, ORFs tend to become shorter than becoming longer. Therefore, long ORFs are probably selected by evolution to be retained in the genome.