scholarly journals Uncovering de novo gene birth in yeast using deep transcriptomics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
William R. Blevins ◽  
Jorge Ruiz-Orera ◽  
Xavier Messeguer ◽  
Bernat Blasco-Moreno ◽  
José Luis Villanueva-Cañas ◽  
...  
Keyword(s):  
De Novo ◽  
Yeast Species ◽  
Large Fraction ◽  
Raw Material ◽  
Opposite Orientation ◽  
New Genes ◽  
Small Proteins ◽  
De Novo Genes ◽  
De Novo Gene ◽  
Response To Stress

AbstractDe 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.

scholarly journals Fast turnover of genome transcription across evolutionary time exposes entire non-coding DNA to de novo gene emergence

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Rafik Neme ◽  
Diethard Tautz
Keyword(s):  
De Novo ◽  
Gene Evolution ◽  
Large Fraction ◽  
Phylogenetic Distance ◽  
Evolutionary Time ◽  
High Turnover ◽  
Entire Genome ◽  
De Novo Gene ◽  
Phylogenetic Level ◽  
Transcriptome Coverage

Deep sequencing analyses have shown that a large fraction of genomes is transcribed, but the significance of this transcription is much debated. Here, we characterize the phylogenetic turnover of poly-adenylated transcripts in a comprehensive sampling of taxa of the mouse (genus Mus), spanning a phylogenetic distance of 10 Myr. Using deep RNA sequencing we find that at a given sequencing depth transcriptome coverage becomes saturated within a taxon, but keeps extending when compared between taxa, even at this very shallow phylogenetic level. Our data show a high turnover of transcriptional states between taxa and that no major transcript-free islands exist across evolutionary time. This suggests that the entire genome can be transcribed into poly-adenylated RNA when viewed at an evolutionary time scale. We conclude that any part of the non-coding genome can potentially become subject to evolutionary functionalization via de novo gene evolution within relatively short evolutionary time spans.

scholarly journals De novo birth of functional, human-specific microproteins

2021 ◽  
Author(s):  
Nikolaos Vakirlis ◽  
Kate M. Duggan ◽  
Aoife McLysaght
Keyword(s):  
Transcriptional Activation ◽  
De Novo ◽  
Genomic Analysis ◽  
Open Reading Frames ◽  
Animal Evolution ◽  
Evolutionary Origins ◽  
Small Proteins ◽  
De Novo Gene ◽  
Small Open Reading Frames ◽  
Human Specific

We now have a growing understanding that functional short proteins can be translated out of small Open Reading Frames (sORF). Such ″microproteins″ can perform crucial biological tasks and can have considerable phenotypic consequences. However, their size makes them less amenable to genomic analysis, and their evolutionary 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 non-coding sequence. Here we test the possibility that de novo gene birth can produce microproteins that are functional ″out-of-the-box″. We reconstructed the evolutionary origins of human microproteins previously found to have measurable, statistically significant fitness effects. By tracing the appearance of each ORF and its transcriptional activation, we were able to show that, indeed, novel small proteins with significant phenotypic effects have emerged de novo throughout animal evolution, including many after the human-chimpanzee split. We show that traditional methods for assessing the coding potential of such sequences often fall short, due to the high variability present in the alignments and the absence of telltale evolutionary signatures that are not yet measurable. Thus we provide evidence that the functional potential intrinsic to sORFs can be rapidly, and frequently realised through de novo gene birth.

scholarly journals Comparative transcriptomics and ribo-seq: Looking at de novo gene emergence in Saccharomycotina

2017 ◽  
Author(s):  
William Blevins ◽  
Mar Albà ◽  
Lucas Carey
Keyword(s):  
De Novo ◽  
Ribosome Profiling ◽  
Rna Seq ◽  
De Novo Genes ◽  
De Novo Gene ◽  
Rich Media ◽  
Conserved Genes ◽  
Different Depths ◽  
Yeast Phylogeny ◽  
And Oxidative Stress

In de novo gene emergence, a segment of non-coding DNA undergoes a series of changes which enables transcription, potentially leading to a new protein that could eventually acquire a novel function. Due to their recent origins, young de novo genes have no homology with other genes. Furthermore, de novo genes may not initially be under the same selective constraints as other genes. Dozens of de novo genes have recently been identified in many diverse species; however, the mechanisms leading to their appearance are not yet well understood. To study this phenomenon, we have performed deep RNA sequencing (RNA-seq) on 11 species of yeast from the phylum of Ascomycota in both rich media and oxidative stress conditions. Furthermore, we performed ribosome profiling (Ribo-seq) experiments in both conditions with S. cerevisiae. These data have been used to classify the conservation of genes at different depths in the yeast phylogeny. Hundreds of genes in each species were novel (unannotated), and many were identified as putative de novo genes; these candidates were then tested for signals of translation using our Ribo-seq data. We show that putative de novo genes have different properties relative to phylogenetically conserved genes. This comparative phylotranscriptomic analysis advances our understanding of de novo gene origins.

scholarly journals Run or Die in the Evolution of New MicroRNAs—Testing the Red Queen Hypothesis on De Novo New Genes

2020 ◽  
Author(s):  
Yixin Zhao ◽  
Guang-An Lu ◽  
Hao Yang ◽  
Pei Lin ◽  
Zhongqi Liufu ◽  
...  
Keyword(s):  
De Novo ◽  
Red Queen Hypothesis ◽  
Knockout Mutant ◽  
Red Queen ◽  
Fitness Components ◽  
New Genes ◽  
Rates Of Evolution ◽  
De Novo Genes ◽  
The Red Queen ◽  
Very High

Abstract The Red Queen hypothesis depicts evolution as the continual struggle to adapt. According to this hypothesis, new genes, especially those originating from nongenic sequences (i.e., de novo genes), are eliminated unless they evolve continually in adaptation to a changing environment. Here, we analyze two Drosophila de novo miRNAs that are expressed in a testis-specific manner with very high rates of evolution in their DNA sequence. We knocked out these miRNAs in two sibling species and investigated their contributions to different fitness components. We observed that the fitness contributions of miR-975 in Drosophila simulans seem positive, in contrast to its neutral contributions in D. melanogaster, whereas miR-983 appears to have negative contributions in both species, as the fitness of the knockout mutant increases. As predicted by the Red Queen hypothesis, the fitness difference of these de novo miRNAs indicates their different fates.

scholarly journals Comparative transcriptomics and ribo-seq: Looking at de novo gene emergence in Saccharomycotina

2017 ◽  
Author(s):  
William Blevins ◽  
Mar Albà ◽  
Lucas Carey
Keyword(s):  
De Novo ◽  
Ribosome Profiling ◽  
Rna Seq ◽  
De Novo Genes ◽  
De Novo Gene ◽  
Rich Media ◽  
Conserved Genes ◽  
Different Depths ◽  
Yeast Phylogeny ◽  
And Oxidative Stress

In de novo gene emergence, a segment of non-coding DNA undergoes a series of changes which enables transcription, potentially leading to a new protein that could eventually acquire a novel function. Due to their recent origins, young de novo genes have no homology with other genes. Furthermore, de novo genes may not initially be under the same selective constraints as other genes. Dozens of de novo genes have recently been identified in many diverse species; however, the mechanisms leading to their appearance are not yet well understood. To study this phenomenon, we have performed deep RNA sequencing (RNA-seq) on 11 species of yeast from the phylum of Ascomycota in both rich media and oxidative stress conditions. Furthermore, we performed ribosome profiling (Ribo-seq) experiments in both conditions with S. cerevisiae. These data have been used to classify the conservation of genes at different depths in the yeast phylogeny. Hundreds of genes in each species were novel (unannotated), and many were identified as putative de novo genes; these candidates were then tested for signals of translation using our Ribo-seq data. We show that putative de novo genes have different properties relative to phylogenetically conserved genes. This comparative phylotranscriptomic analysis advances our understanding of de novo gene origins.

scholarly journals Testis single-cell RNA-seq reveals the dynamics of de novo gene transcription and germline mutational bias in Drosophila

2019 ◽  
Author(s):  
Evan Witt ◽  
Sigi Benjamin ◽  
Nicolas Svetec ◽  
Li Zhao
Keyword(s):  
Single Cell ◽  
De Novo ◽  
Gene Evolution ◽  
Expression Patterns ◽  
Reproductive Function ◽  
Cell Types ◽  
Mutational Bias ◽  
Evolutionary Innovation ◽  
New Genes ◽  
De Novo Gene

SummaryThe testis is a peculiar tissue in many respects. It shows patterns of rapid gene evolution and provides a hotspot for the origination of genetic novelties such as de novo genes, duplications and mutations. To investigate the expression patterns of genetic novelties across cell types, we performed single-cell RNA-sequencing of adult Drosophila testis. We found that new genes were expressed in various cell types, the patterns of which may be influenced by their mode of origination. In particular, lineage-specific de novo genes are commonly expressed in early spermatocytes, while young duplicated genes are often bimodally expressed. Analysis of germline substitutions suggests that spermatogenesis is a highly reparative process, with the mutational load of germ cells decreasing as spermatogenesis progresses. By elucidating the distribution of genetic novelties across spermatogenesis, this study provides a deeper understanding of how the testis maintains its core reproductive function while being a hotbed of evolutionary innovation.

scholarly journals De novo gene evolution: How do we transition from non-coding to coding?

2017 ◽  
Author(s):  
Jorge Ruiz-Orera ◽  
José Luis Villanueva-Cañas ◽  
William Blevins ◽  
M.Mar Albà
Keyword(s):  
De Novo ◽  
Gene Evolution ◽  
Neutral Evolution ◽  
Functional Protein ◽  
Protein Coding ◽  
Coding Sequences ◽  
Sequence Composition ◽  
Protein Coding Genes ◽  
Small Proteins ◽  
De Novo Gene

Recent years have witnessed the discovery of protein–coding genes which appear to have evolved de novo from previously non-coding sequences. This has changed the long-standing view that coding sequences can only evolve from other coding sequences. However, there are still many open questions regarding how new protein-coding sequences can arise from non-genic DNA. Two prerequisites for the birth of a new functional protein-coding gene are that the corresponding DNA fragment is transcribed and that it is also translated. Transcription is known to be pervasive in the genome, producing a large number of transcripts that do not correspond to conserved protein-coding genes, and which are usually annotated as long non-coding RNAs (lncRNA). Recently, sequencing of ribosome protected fragments (Ribo-Seq) has provided evidence that many of these transcripts actually translate small proteins. We have used mouse non-synonymous and synonymous variation data to estimate the strength of purifying selection acting on the translated open reading frames (ORFs). Whereas a subset of the lncRNAs are likely to actually be true protein-coding genes (and thus previously misclassified), the bulk of lncRNAs code for proteins which show variation patterns consistent with neutral evolution. We also show that the ORFs that have a more favorable, coding-like, sequence composition are more likely to be translated than other ORFs in lncRNAs. This study provides strong evidence that there is a large and ever-changing reservoir of lowly abundant proteins; some of these peptides may become useful and act as seeds for de novo gene evolution.

scholarly journals From de novo to ‘de nono’: most novel protein coding genes identified with phylostratigraphy represent old genes or recent duplicates

2018 ◽  
Author(s):  
Claudio Casola
Keyword(s):  
De Novo ◽  
Sequence Similarity ◽  
Gc Content ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Gene Sets ◽  
De Novo Genes ◽  
De Novo Gene ◽  
Similarity Searches ◽  
Novel Protein

AbstractThe evolution of novel protein-coding genes from noncoding regions of the genome is one of the most compelling evidence for genetic innovations in nature. One popular approach to identify de novo genes is phylostratigraphy, which consists of determining the approximate time of origin (age) of a gene based on its distribution along a species phylogeny. Several studies have revealed significant flaws in determining the age of genes, including de novo genes, using phylostratigraphy alone. However, the rate of false positives in de novo gene surveys, based on phylostratigraphy, remains unknown. Here, I re-analyze the findings from three studies, two of which identified tens to hundreds of rodent-specific de novo genes adopting a phylostratigraphy-centered approach. Most of the putative de novo genes discovered in these investigations are no longer included in recently updated mouse gene sets. Using a combination of synteny information and sequence similarity searches, I show that about 60% of the remaining 381 putative de novo genes share homology with genes from other vertebrates, originated through gene duplication, and/or share no synteny information with non-rodent mammals. These results led to an estimated rate of ∼12 de novo genes per million year in mouse. Contrary to a previous study (Wilson et al. 2017), I found no evidence supporting the preadaptation hypothesis of de novo gene formation. Nearly half of the de novo genes confirmed in this study are within older genes, indicating that co-option of preexisting regulatory regions and a higher GC content may facilitate the origin of novel genes.

scholarly journals Testis single-cell RNA-seq reveals the dynamics of de novo gene transcription and germline mutational bias in Drosophila

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Evan Witt ◽  
Sigi Benjamin ◽  
Nicolas Svetec ◽  
Li Zhao
Keyword(s):  
Single Cell ◽  
De Novo ◽  
Gene Evolution ◽  
Expression Patterns ◽  
Reproductive Function ◽  
Cell Types ◽  
Mutational Bias ◽  
Evolutionary Innovation ◽  
New Genes ◽  
De Novo Genes

The testis is a peculiar tissue in many respects. It shows patterns of rapid gene evolution and provides a hotspot for the origination of genetic novelties such as de novo genes, duplications and mutations. To investigate the expression patterns of genetic novelties across cell types, we performed single-cell RNA-sequencing of adult Drosophila testis. We found that new genes were expressed in various cell types, the patterns of which may be influenced by their mode of origination. In particular, lineage-specific de novo genes are commonly expressed in early spermatocytes, while young duplicated genes are often bimodally expressed. Analysis of germline substitutions suggests that spermatogenesis is a highly reparative process, with the mutational load of germ cells decreasing as spermatogenesis progresses. By elucidating the distribution of genetic novelties across spermatogenesis, this study provides a deeper understanding of how the testis maintains its core reproductive function while being a hotbed of evolutionary innovation.

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