scholarly journals New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation

2015 ◽  
Vol 370 (1678) ◽  
pp. 20140332 ◽  
Author(s):  
Aoife McLysaght ◽  
Daniele Guerzoni
Keyword(s):  
De Novo ◽  
Complex Structure ◽  
Protein Coding ◽  
Functional Roles ◽  
Protein Coding Genes ◽  
Evolutionary Innovation ◽  
New Genes ◽  
De Novo Genes ◽  
Novel Protein

The origin of novel protein-coding genes de novo was once considered so improbable as to be impossible. In less than a decade, and especially in the last five years, this view has been overturned by extensive evidence from diverse eukaryotic lineages. There is now evidence that this mechanism has contributed a significant number of genes to genomes of organisms as diverse as Saccharomyces , Drosophila , Plasmodium , Arabidopisis and human. From simple beginnings, these genes have in some instances acquired complex structure, regulated expression and important functional roles. New genes are often thought of as dispensable late additions; however, some recent de novo genes in human can play a role in disease. Rather than an extremely rare occurrence, it is now evident that there is a relatively constant trickle of proto-genes released into the testing ground of natural selection. It is currently unknown whether de novo genes arise primarily through an ‘RNA-first’ or ‘ORF-first’ pathway. Either way, evolutionary tinkering with this pool of genetic potential may have been a significant player in the origins of lineage-specific traits and adaptations.

scholarly journals De novoemergence of adaptive membrane proteins from thymine-rich intergenic sequences

2019 ◽  
Author(s):  
Nikolaos Vakirlis ◽  
Omer Acar ◽  
Brian Hsu ◽  
Nelson Castilho Coelho ◽  
S. Branden Van Oss ◽  
...  
Keyword(s):  
De Novo ◽  
Transmembrane Proteins ◽  
Protein Coding ◽  
Coding Sequences ◽  
Beneficial Effects ◽  
Protein Coding Genes ◽  
Evolutionary Innovation ◽  
Intergenic Sequences ◽  
Intergenic Regions ◽  
Novel Protein

SummaryRecent evidence demonstrates that novel protein-coding genes can arisede novofrom intergenic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of intergenic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Do intergenic translation events yield polypeptides with useful biochemical capacities? The answer to this question remains controversial. Here, we systematically characterized howde novoemerging coding sequences impact fitness. In budding yeast, overexpression of these sequences was enriched in beneficial effects, while their disruption was generally inconsequential. We found that beneficial emerging sequences have a strong tendency to encode putative transmembrane proteins, which appears to stem from a cryptic propensity for transmembrane signals throughout thymine-rich intergenic regions of the genome. These findings suggest that novel genes with useful biochemical capacities, such as transmembrane domains, tend to evolvede novowithin intergenic loci that already harbored a blueprint for these capacities.

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 A de novo evolved gene in the house mouse regulates female pregnancy cycles

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Chen Xie ◽  
Cemalettin Bekpen ◽  
Sven Künzel ◽  
Maryam Keshavarz ◽  
Rebecca Krebs-Wheaton ◽  
...  
Keyword(s):  
House Mouse ◽  
De Novo ◽  
Specific Protein ◽  
Ribosome Profiling ◽  
Mass Spectrometry Data ◽  
Preimplantation Embryos ◽  
Protein Coding ◽  
Reading Frame ◽  
Protein Coding Genes ◽  
New Genes

The de novo emergence of new genes has been well documented through genomic analyses. However, a functional analysis, especially of very young protein-coding genes, is still largely lacking. Here, we identify a set of house mouse-specific protein-coding genes and assess their translation by ribosome profiling and mass spectrometry data. We functionally analyze one of them, Gm13030, which is specifically expressed in females in the oviduct. The interruption of the reading frame affects the transcriptional network in the oviducts at a specific stage of the estrous cycle. This includes the upregulation of Dcpp genes, which are known to stimulate the growth of preimplantation embryos. As a consequence, knockout females have their second litters after shorter times and have a higher infanticide rate. Given that Gm13030 shows no signs of positive selection, our findings support the hypothesis that a de novo evolved gene can directly adopt a function without much sequence adaptation.

scholarly journals De novo emergence of adaptive membrane proteins from thymine-rich genomic sequences

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Nikolaos Vakirlis ◽  
Omer Acar ◽  
Brian Hsu ◽  
Nelson Castilho Coelho ◽  
S. Branden Van Oss ◽  
...  
Keyword(s):  
Natural Selection ◽  
De Novo ◽  
Natural Populations ◽  
Evolutionary Model ◽  
Transmembrane Domains ◽  
Protein Coding ◽  
Fitness Effects ◽  
Evolutionary Innovation ◽  
Intergenic Regions ◽  
Novel Protein

AbstractRecent evidence demonstrates that novel protein-coding genes can arise de novo from non-genic loci. This evolutionary innovation is thought to be facilitated by the pervasive translation of non-genic transcripts, which exposes a reservoir of variable polypeptides to natural selection. Here, we systematically characterize how these de novo emerging coding sequences impact fitness in budding yeast. Disruption of emerging sequences is generally inconsequential for fitness in the laboratory and in natural populations. Overexpression of emerging sequences, however, is enriched in adaptive fitness effects compared to overexpression of established genes. We find that adaptive emerging sequences tend to encode putative transmembrane domains, and that thymine-rich intergenic regions harbor a widespread potential to produce transmembrane domains. These findings, together with in-depth examination of the de novo emerging YBR196C-A locus, suggest a novel evolutionary model whereby adaptive transmembrane polypeptides emerge de novo from thymine-rich non-genic regions and subsequently accumulate changes molded by natural selection.

scholarly journals Contribution of Retrotransposition to Developmental Disorders

2018 ◽  
Author(s):  
Eugene J. Gardner ◽  
Elena Prigmore ◽  
Giuseppe Gallone ◽  
Petr Danecek ◽  
Kaitlin E. Samocha ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Purifying Selection ◽  
Mobile Genetic Elements ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Genome Wide ◽  
The Impact ◽  
Transcribed Sequences

AbstractMobile genetic Elements (MEs) are segments of DNA which, through an RNA intermediate, can generate new copies of themselves and other transcribed sequences through the process of retrotransposition (RT). In humans several disorders have been attributed to RT, but the role of RT in severe developmental disorders (DD) has not yet been explored. As such, we have identified RT-derived events in 9,738 exome sequenced trios with DD-affected probands as part of the Deciphering Developmental Disorders (DDD) study. We have ascertained 9 de novo MEs, 4 of which are likely causative of the patient’s symptoms (0.04% of probands), as well as 2 de novo gene retroduplications. Beyond identifying likely diagnostic RT events, we have estimated genome-wide germline ME mutagenesis and constraint and demonstrated that coding RT events have signatures of purifying selection equivalent to those of truncating mutations. Overall, our analysis represents a comprehensive interrogation of the impact of retrotransposition on protein coding genes and a framework for future evolutionary and disease studies.

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.

scholarly journals New genes and functional innovation in mammals

2016 ◽  
Author(s):  
José Luis Villanueva-Cañas ◽  
Jorge Ruiz-Orera ◽  
M.Isabel Agea ◽  
Maria Gallo ◽  
David Andreu ◽  
...  
Keyword(s):  
De Novo ◽  
Gene Families ◽  
Specific Gene ◽  
Protein Coding ◽  
Evolutionary Innovation ◽  
New Genes ◽  
Recent Origin ◽  
Mammalian Genes ◽  
Genomic Regions ◽  
New Protein

ABSTRACTThe birth of genes that encode new protein sequences is a major source of evolutionary innovation. However, we still understand relatively little about how these genes come into being and which functions they are selected for. To address these questions we have obtained a large collection of mammalian-specific gene families that lack homologues in other eukaryotic groups. We have combined gene annotations and de novo transcript assemblies from 30 different mamalian species, obtaining about 6,000 gene families. In general, the proteins in mammalian-specific gene families tend to be short and depleted in aromatic and negatively charged residues. Proteins which arose early in mammalian evolution include milk and skin polypeptides, immune response components, and proteins involved in reproduction. In contrast, the functions of proteins which have a more recent origin remain largely unknown, despite the fact that these proteins also have extensive proteomics support. We identify several previously described cases of genes originated de novo from non-coding genomic regions, supporting the idea that this mechanism frequently underlies the evolution of new protein-coding genes in mammals. Finally, we show that most young mammalian genes are preferentially expressed in testis, suggesting that sexual selection plays an important role in the emergence of new functional genes.

scholarly journals Positive natural selection of N6-methyladenosine on the RNAs of processed pseudogenes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Liqiang Tan ◽  
Weisheng Cheng ◽  
Fang Liu ◽  
Dan Ohtan Wang ◽  
Linwei Wu ◽  
...  
Keyword(s):  
De Novo ◽  
Rna Degradation ◽  
Rna Modification ◽  
Protein Coding ◽  
Nonsense Mediated Decay ◽  
Protein Coding Genes ◽  
Processed Pseudogene ◽  
Processed Pseudogenes ◽  
Cognate Protein

Abstract Background Canonical nonsense-mediated decay (NMD) is an important splicing-dependent process for mRNA surveillance in mammals. However, processed pseudogenes are not able to trigger NMD due to their lack of introns. It is largely unknown whether they have evolved other surveillance mechanisms. Results Here, we find that the RNAs of pseudogenes, especially processed pseudogenes, have dramatically higher m6A levels than their cognate protein-coding genes, associated with de novo m6A peaks and motifs in human cells. Furthermore, pseudogenes have rapidly accumulated m6A motifs during evolution. The m6A sites of pseudogenes are evolutionarily younger than neutral sites and their m6A levels are increasing, supporting the idea that m6A on the RNAs of pseudogenes is under positive selection. We then find that the m6A RNA modification of processed, rather than unprocessed, pseudogenes promotes cytosolic RNA degradation and attenuates interference with the RNAs of their cognate protein-coding genes. We experimentally validate the m6A RNA modification of two processed pseudogenes, DSTNP2 and NAP1L4P1, which promotes the RNA degradation of both pseudogenes and their cognate protein-coding genes DSTN and NAP1L4. In addition, the m6A of DSTNP2 regulation of DSTN is partially dependent on the miRNA miR-362-5p. Conclusions Our discovery reveals a novel evolutionary role of m6A RNA modification in cleaning up the unnecessary processed pseudogene transcripts to attenuate their interference with the regulatory network of protein-coding genes.

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