Origins, evolution, and physiological implications of de novo genes in yeast

Abstract

De novo gene birth is the process by which new genes emerge in sequences that were previously noncoding. Over the past decade, researchers have taken advantage of the power of yeast as a model and a tool to study the evolutionary mechanisms and physiological implications of de novo gene birth. We summarize the mechanisms that have been proposed to explicate how noncoding sequences can become protein‐coding genes, highlighting the discovery of pervasive translation of the yeast transcriptome and its presumed impact on evolutionary innovation. We summarize current best practices for the identification and characterization of de novo genes. Crucially, we explain that the field is still in its nascency, with the physiological roles of most young yeast de novo genes identified thus far still utterly unknown. We hope this review inspires researchers to investigate the true contribution of de novo gene birth to cellular physiology and phenotypic diversity across yeast strains and species.

Four classic “de novo” genes all have plausible homologs and likely evolved from retro-duplicated or pseudogenic sequences

“…Although once not seriously considered as being likely (Kaessmann 2010), the de novo origination of entire genes from non-genic DNA has since become a dogma in the study of molecular evolution (Cherezov et al 2021). This would apparently defy the expectation of Jacob (1977) namely that, “the probability that a functional protein would appear de novo by the random association of amino acids is practically zero.” This has resulted in extensive searches for candidate de novo genes, and evolving “proto-genes”, in all species (Parikh et al 2022). Part of the problem here has been that researchers in the field have relied too heavily on similarity search tools, like BLAST, when trying to find out or rule out potential antecedents.…”

The Ribosome Profiling landscape of yeast reveals a high diversity in pervasive translation

“…Furthermore, hundreds of novel peptides or microproteins resulting from presumed noncoding regions have been detected with proteomics, further supporting the pervasivity of translation 19,[26][27][28][29][30][31][32] . Finally, many studies report examples of de novo gene birth from noncoding regions in eukaryotic species 24 . These de novo genes exhibit clear regulation patterns, have been shown to be subject to negative selection and a function has been reported for some of them, confirming that they could undoubtedly be associated with the coding world 34,35,59,43,60,57 .…”

“…Precisely, OMICS technologies have provided a huge amount of data revealing the "omnipresence" of biological noise which has turned out to result from the pervasivity of biological processes. As a matter of fact, noncoding regions have been shown to be pervasively transcribed and translated, exposing non-genic sequences to selection 4,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] . Furthermore, hundreds of novel peptides or microproteins resulting from presumed noncoding regions have been detected with proteomics, further supporting the pervasivity of translation 19,[26][27][28][29][30][31][32] .…”

Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection.

“…For instance, in yeast, some de novo genes (BSC4 and MDF1) play roles in DNA repair process [19][20][21]. In Drosophila species, lineage-specific genes can control the key cytological process of mitosis [22].…”

“…New genes can integrate into biologically critical processes, such as transcription regulation, RNA synthesis, and DNA repair (Ciccarelli et al 2005; Ding et al 2021). For instance, in yeast, some de novo genes play roles in DNA repair process (Cai et al 2008; Li et al 2010; Parikh et al 2022). In Drosophila species, lineage-specific genes can control the key cytological process of mitosis (Ross et al 2013).…”