Proto-genes and de novo gene birth

Abstract

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo1,2. Processes involving re-organization of pre-existing genes, notably following gene duplication, have been extensively described1,2. In contrast, de novo gene birth remains poorly understood, mainly because translation of sequences devoid of genes, or “non-genic” sequences, is expected to produce insignificant polypeptides rather than proteins with specific biological functions1,3-6. Here, we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes4 generated by widespread translational activity in non-genic sequences. Testing this model at genome-scale in Saccharomyces cerevisiae, we detect translation of hundreds of short species-specific open reading frames (ORFs) located in non-genic sequences. These translation events appear to provide adaptive potential7, as suggested by their differential regulation upon stress and by signatures of retention by natural selection. In line with our model, we establish that S. cerevisiae ORFs can be placed within an evolutionary continuum ranging from non-genic sequences to genes. We identify ~1,900 candidate proto-genes among S. cerevisiae ORFs and find that de novo gene birth from such a reservoir may be more prevalent than sporadic gene duplication. Our work illustrates that evolution exploits seemingly dispensable sequences to generate adaptive functional innovation.

Biophysics of protein evolution and evolutionary protein biophysics

“…Apart from point mutations, mobile genetic elements are likely to play a crucial role in providing exaptations [380][381][382]. Each genome appears to constantly produce transcribed and translated 'proto-genes' that arise by chance, some of which may be exapted by evolution for a certain function [383]. It follows that a major part of the enhancement of evolvability by mutational robustness is based on the evolutionary potential provided by conformational dynamics at the level of a single sequence when excited-state structures of a protein [173,[384][385][386] ( §2.9) with beneficial function come under natural selection.…”

Multi-step formation, evolution, and functionalization of new cytoplasmic male sterility genes in the plant mitochondrial genomes

“…New nuclear genes may evolve through transitory protogenes [32,37]. In this study we show the first case of protogenes identified in eukaryotic cytoplasmic genomes, and suggest that the generation of protogenes, as well as SSS, had served as a buffer, thus could also be a critical step for the establishment of CMS genes in natural populations.…”

Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists

“…The latter diverged from the L. bicolor lineage ~20 million years ago 18 , thus indicating that even after the evolution of the ECM habit species within a genus continued to develop a specific symbiosis protein 'toolkit' and to diverge from each other. Lineagespecific orphan genes may represent either ancestral genes that have diverged so far that their similarities to other sequences have been obscured, a phenomenon frequently observed for effector genes 19 , or genes formed de novo from previously noncoding sequences 20 . Orphan fungal genes are over-represented among up-and downregulated genes found in mycorrhizal roots (Figs.…”