Proto-genes and de novo gene birth

By Anne-Ruxandra Carvunis, T. Rolland, I. Wapinski, M. Calderwood, Muhammed A. Yıldırım, Nicolas Simonis, B. Charloteaux, César A. Hidalgo, J. Barbette, Balaji Santhanam and 6 more. Nature, 2012

619 citations recorded by the source corpus.

Novel protein-coding genes can arise either through re-organization of pre-existing genes or de novo. Processes involving re-organization of pre-existing genes, notably after gene duplication, have been extensively described. 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 functions. Here we formalize an evolutionary model according to which functional genes evolve de novo through transitory proto-genes generated by widespread translational activity in non-genic sequences. Testing this model at the 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 seem to provide adaptive potential, 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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/60715131374c0392f266e177bdf9312757495273

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In Molecular Biology

Citations in the corpus

Long Noncoding RNAs: Past, Present, and Future (2013, background): “…nt) and poorly conserved (found only in the closest relatives of S. cerevisiae and with no sequence similarities to any known genes) ORFs that are nonetheless translated, as assayed by ribosome profiling, but only less than one-quarter show any sign of purifying selection (Carvunis et al. 2012).”
Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists (2015, background): “Lineage-specific 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 .”
Natural protein sequences are more intrinsically disordered than random sequences (2016, background): “Investigating random sequences is also important because some proteins can arise suddenly from non-coding regions [3, 4].”
Ribosome profiling provides evidence that large non-coding RNAs do not encode proteins (2013, background): “…and Morris, 1994), contribute to the antigenic potential of pathogens (Starck et al., 2008), regulate mRNA stability by inducing nonsensemediated decay (Smith and Steitz, 1998), and may even serve as a source of proto-proteins enabling the evolution of novel proteins (Carvunis et al., 2012).”
Hierarchical cooperation of transcription factors from integration analysis of DNA sequences, ChIP-Seq and ChIA-PET data (2019, background): “De novo genes are also believed to emerge through the evolution of lineages [39].”