De novo gene birth.
Ontology highlight
ABSTRACT:
SUBMITTER: Van Oss SB
PROVIDER: S-EPMC6542195 | biostudies-literature | 2019 May
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC3401362 | biostudies-literature
Project description:De novo gene origination has been recently established as an important mechanism for the formation of new genes. In organisms with a large genome, intergenic and intronic regions provide plenty of raw material for new transcriptional events to occur, but little is know about how de novo transcripts originate in more densely-packed genomes. Here, we identify 213 de novo originated transcripts in Saccharomyces cerevisiae using deep transcriptomics and genomic synteny information from multiple yeast species grown in two different conditions. We find that about half of the de novo transcripts are expressed from regions which already harbor other genes in the opposite orientation; these transcripts show similar expression changes in response to stress as their overlapping counterparts, and some appear to translate small proteins. Thus, a large fraction of de novo genes in yeast are likely to co-evolve with already existing genes.
| S-EPMC7841160 | biostudies-literature
Project description:The source of genetic novelty is an area of wide interest and intense investigation. Although gene duplication is conventionally thought to dominate the production of new genes, this view was recently challenged by a proposal of widespread de novo gene origination in eukaryotic evolution. Specifically, distributions of various gene properties such as coding sequence length, expression level, codon usage, and probability of being subject to purifying selection among groups of genes with different estimated ages were reported to support a model in which new protein-coding proto-genes arise from noncoding DNA and gradually integrate into cellular networks. Here we show that the genomic patterns asserted to support widespread de novo gene origination are largely attributable to biases in gene age estimation by phylostratigraphy, because such patterns are also observed in phylostratigraphic analysis of simulated genes bearing identical ages. Furthermore, there is no evidence of purifying selection on very young de novo genes previously claimed to show such signals. Together, these findings are consistent with the prevailing view that de novo gene birth is a relatively minor contributor to new genes in genome evolution. They also illustrate the danger of using phylostratigraphy in the study of new gene origination without considering its inherent bias.
| S-EPMC5010002 | biostudies-literature
Project description:Preterm birth (PTB) affects ~12% of pregnancies in the US. Despite its high mortality and morbidity, the molecular etiology underlying PTB has been unclear. Numerous studies have been devoted to identifying genetic factors in maternal and fetal genomes, but so far few genomic loci have been associated with PTB. By analyzing whole-genome sequencing data from 816 trio families, for the first time, we observed the role of fetal de novo mutations in PTB. We observed a significant increase in de novo mutation burden in PTB fetal genomes. Our genomic analyses further revealed that affected genes by PTB de novo mutations were dosage sensitive, intolerant to genomic deletions, and their mouse orthologs were likely developmentally essential. These genes were significantly involved in early fetal brain development, which was further supported by our analysis of copy number variants identified from an independent PTB cohort. Our study indicates a new mechanism in PTB occurrence independently contributed from fetal genomes, and thus opens a new avenue for future PTB research.
| S-EPMC5384656 | biostudies-literature
Project description:Regulatory networks control the spatiotemporal gene expression patterns that give rise to and define the individual cell types of multicellular organisms. In eumetazoa, distal regulatory elements called enhancers play a key role in determining the structure of such networks, particularly the wiring diagram of "who regulates whom." Mutations that affect enhancer activity can therefore rewire regulatory networks, potentially causing adaptive changes in gene expression. Here, we use whole-tissue and single-cell transcriptomic and chromatin accessibility data from mouse to show that enhancers play an additional role in the evolution of regulatory networks: They facilitate network growth by creating transcriptionally active regions of open chromatin that are conducive to de novo gene evolution. Specifically, our comparative transcriptomic analysis with three other mammalian species shows that young, mouse-specific intergenic open reading frames are preferentially located near enhancers, whereas older open reading frames are not. Mouse-specific intergenic open reading frames that are proximal to enhancers are more highly and stably transcribed than those that are not proximal to enhancers or promoters, and they are transcribed in a limited diversity of cellular contexts. Furthermore, we report several instances of mouse-specific intergenic open reading frames proximal to promoters showing evidence of being repurposed enhancers. We also show that open reading frames gradually acquire interactions with enhancers over macroevolutionary timescales, helping integrate genes-those that have arisen de novo or by other means-into existing regulatory networks. Taken together, our results highlight a dual role of enhancers in expanding and rewiring gene regulatory networks.
| S-EPMC7086177 | biostudies-literature
Project description:The noncoding genome plays an important role in de novo gene birth and in the emergence of genetic novelty. Nevertheless, how noncoding sequences' properties could promote the birth of novel genes and shape the evolution and the structural diversity of proteins remains unclear. Therefore, by combining different bioinformatic approaches, we characterized the fold potential diversity of the amino acid sequences encoded by all intergenic open reading frames (ORFs) of S. cerevisiae with the aim of (1) exploring whether the structural states' diversity of proteomes is already present in noncoding sequences, and (2) estimating the potential of the noncoding genome to produce novel protein bricks that could either give rise to novel genes or be integrated into pre-existing proteins, thus participating in protein structure diversity and evolution. We showed that amino acid sequences encoded by most yeast intergenic ORFs contain the elementary building blocks of protein structures. Moreover, they encompass the large structural state diversity of canonical proteins, with the majority predicted as foldable. Then, we investigated the early stages of de novo gene birth by reconstructing the ancestral sequences of 70 yeast de novo genes and characterized the sequence and structural properties of intergenic ORFs with a strong translation signal. This enabled us to highlight sequence and structural factors determining de novo gene emergence. Finally, we showed a strong correlation between the fold potential of de novo proteins and one of their ancestral amino acid sequences, reflecting the relationship between the noncoding genome and the protein structure universe.
| S-EPMC8647833 | biostudies-literature
Project description:The phenomenon of de novo gene birth from junk DNA is surprising, because random polypeptides are expected to be toxic. There are two conflicting views about how de novo gene birth is nevertheless possible: the continuum hypothesis invokes a gradual gene birth process, while the preadaptation hypothesis predicts that young genes will show extreme levels of gene-like traits. We show that intrinsic structural disorder conforms to the predictions of the preadaptation hypothesis and falsifies the continuum hypothesis, with all genes having higher levels than translated junk DNA, but young genes having the highest level of all. Results are robust to homology detection bias, to the non-independence of multiple members of the same gene family, and to the false positive annotation of protein-coding genes.
| S-EPMC5476217 | biostudies-literature
Project description:Small open reading frames (sORFs) can encode functional "microproteins" that perform crucial biological tasks. However, their size makes them less amenable to genomic analysis, and their origins and conservation are poorly understood. Given their short length, it is plausible that some of these functional microproteins have recently originated entirely de novo from noncoding sequences. Here we sought to identify such cases in the human lineage by reconstructing the evolutionary origins of human microproteins previously found to have measurable, statistically significant fitness effects. By tracing the formation of each ORF and its transcriptional activation, we show that novel microproteins with significant phenotypic effects have emerged de novo throughout animal evolution, including two after the human-chimpanzee split. Notably, traditional methods for assessing coding potential would miss most of these cases. This evidence demonstrates that the functional potential intrinsic to sORFs can be relatively rapidly and frequently realized through de novo gene emergence.
| S-EPMC10073203 | biostudies-literature
Project description:The noncoding genome plays an important role in de novo gene birth and the emergence of genetic novelty. Nevertheless, how the properties of noncoding sequences could promote the birth of novel genes and shape the structural diversity and evolution of proteins remains unclear. Here, we investigated the potential of the noncoding genome of yeast to produce novel protein bricks that can give rise to novel genes or be integrated in pre-existing proteins, thus participating in protein structure evolution and diversity. Combining different bioinformatics approaches, we showed that intergenic ORFs of yeast encompass the large structural diversity of canonical proteins with the majority encoding peptides predicted as foldable. Then, we investigated the early stages of de novo gene birth with Ribosome Profiling and systematic reconstruction of yeast de novo gene ancestral sequences. We highlighted sequence and structural factors determining de novo gene birth and protein evolution. Finally, we showed a strong correlation between the fold potential of de novo genes and their ancestral ORFs reflecting the relationship between the noncoding genome and the protein structure universe.
2021-09-13 | GSE173861 | GEO
Project description:Proteins are among the most important constituents of biological systems. Because all protein-coding genes have a noncoding ancestral form, the properties of noncoding sequences and how they shape the birth of novel proteins may influence the structure and function of all proteins. Differences between the properties of young proteins and random expectations from noncoding sequences have previously been interpreted as the result of natural selection. However, interpreting such deviations requires a yet-unattained understanding of the raw material of de novo gene birth and its relation to novel functional proteins. We mathematically show that the average properties and selective filtering of the "junk" polypeptides of which this raw material is composed are not the only factors influencing the properties of novel functional proteins. We find that in some biological scenarios, they also depend on the variance of the properties of junk polypeptides and their correlation with the rate of allelic turnover, which may itself depend on mutational biases. This suggests for instance that any property of polypeptides that accelerates their exploration of the sequence space could be overrepresented in novel functional proteins, even if it has a limited effect on adaptive value. To exemplify the use of our general theoretical results, we build a simple model that predicts the mean length and mean intrinsic disorder of novel functional proteins from the genomic GC content and a single evolutionary parameter. This work provides a theoretical framework that can guide the prediction and interpretation of results when studying the de novo emergence of protein-coding genes.
| S-EPMC6707459 | biostudies-literature