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 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 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 Diversity and evolution of the emerging Pandoraviridae family

2017 ◽  
Author(s):  
Matthieu Legendre ◽  
Elisabeth Fabre ◽  
Olivier Poirot ◽  
Sandra Jeudy ◽  
Audrey Lartigue ◽  
...  
Keyword(s):  
Comparative Genomics ◽  
De Novo ◽  
Gene Duplications ◽  
Statistical Features ◽  
Strong Component ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Intergenic Regions ◽  
Comparative Genomics Analysis ◽  
Horizontal Transfers

AbstractWith DNA genomes up to 2.5 Mb packed in particles of bacterium-like shape and dimension, the first two Acanthamoeba-infectingPandoravirusesremained the most spectacular viruses since their description in 2013. Our isolation of three new strains from distant locations and environments allowed us to perform the first comparative genomics analysis of the emerging worldwide-distributed Pandoraviridae family. Thorough annotation of the genomes combining transcriptomic, proteomic, and bioinformatic analyses, led to the discovery of many non-coding transcripts while significantly reducing the former set of predicted protein-coding genes. We found that the Pandoraviridae exhibit an open pan genome, the enormous size of which is not adequately explained by gene duplications or horizontal transfers. As most of the strain specific genes have no extant homolog and exhibit statistical features comparable to intergenic regions, we suggests thatde novogene creation is a strong component in the evolution of the giant Pandoravirus genomes.

scholarly journals Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes

2018 ◽  
Author(s):  
Matthieu Legendre ◽  
Jean-Marie Alempic ◽  
Nadège Philippe ◽  
Audrey Lartigue ◽  
Sandra Jeudy ◽  
...  
Keyword(s):  
De Novo ◽  
Gene Repertoire ◽  
Protein Coding ◽  
Genomic Changes ◽  
Coding Regions ◽  
Protein Coding Genes ◽  
Intergenic Regions ◽  
Mere Existence ◽  
Increasing Functions ◽  
Similar Gene

AbstractWith genomes of up to 2.7 Mb propagated in µm-long oblong particles and initially predicted to encode more than 2000 proteins, members of the Pandoraviridae family display the most extreme features of the known viral world. The mere existence of such giant viruses raises fundamental questions about their origin and the processes governing their evolution. A previous analysis of six newly available isolates, independently confirmed by a study including 3 others, established that the Pandoraviridae pan-genome is open, meaning that each new strain exhibits protein-coding genes not previously identified in other family members. With an average increment of about 60 proteins, the gene repertoire shows no sign of reaching a limit and remains largely coding for proteins without recognizable homologs in other viruses or cells (ORFans). To explain these results, we proposed that most new protein-coding genes were created de novo, from pre-existing non-coding regions of the G+C rich pandoravirus genomes. The comparison of the gene content of a new isolate, P. celtis, closely related (96% identical genome) to the previously described P. quercus is now used to test this hypothesis by studying genomic changes in a microevolution range. Our results confirm that the differences between these two similar gene contents mostly consist of protein-coding genes without known homologs (ORFans), with statistical signatures close to that of intergenic regions. These newborn proteins are under slight negative selection, perhaps to maintain stable folds and prevent protein aggregation pending the eventual emergence of fitness-increasing functions. Our study also unraveled several insertion events mediated by a transposase of the hAT family, 3 copies of which are found in P. celtis and are presumably active. Members of the Pandoraviridae are presently the first viruses known to encode this type of transposase.

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 Yeast de novo genes preferentially emerge from divergently transcribed, GC-rich intergenic regions

2017 ◽  
Author(s):  
Nikolaos Vakirlis N ◽  
Alex S Hebert ◽  
Dana A Opulente ◽  
Guillaume Achaz ◽  
Chris Todd Hittinger ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
De Novo ◽  
Genetic Network ◽  
Protein Coding ◽  
New Genes ◽  
Intergenic Sequences ◽  
Protein Functions ◽  
Intergenic Regions ◽  
Recombination Hot Spots ◽  
Remote Homologs

AbstractNew genes, with novel protein functions, can evolve “from scratch” out of intergenic sequences. These de novo genes can integrate the cell’s genetic network and drive important phenotypic innovations. Therefore, identifying de novo genes and understanding how the transition from noncoding to coding occurs are key problems in evolutionary biology. However, identifying de novo genes is a difficult task, hampered by the presence of remote homologs, fast evolving sequences and erroneously annotated protein coding genes. To overcome these limitations, we developed a procedure that handles the usual pitfalls in de novo gene identification and predicted the emergence of 703 de novo genes in 15 yeast species from two genera whose phylogeny spans at least 100 million years of evolution. We established that de novo gene origination is a widespread phenomenon in yeasts, only a few being ultimately maintained by selection. We validated 82 candidates, by providing new translation evidence for 25 of them through mass spectrometry experiments. We also unambiguously identified the mutations that enabled the transition from non-coding to coding for 30 Saccharomyces de novo genes. We found that de novo genes preferentially emerge next to divergent promoters in GC-rich intergenic regions where the probability of finding a fortuitous and transcribed ORF is the highest. We found a more than 3-fold enrichment of de novo genes at recombination hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic recombination would be a major driving force of de novo gene emergence in yeasts.

scholarly journals Comparative genomic analyses highlight the contribution of pseudogenized protein-coding genes to human lincRNAs

2017 ◽  
Author(s):  
Wan-Hsin Liu ◽  
Zing Tsung-Yeh Tsai ◽  
Huai-Kuang Tsai
Keyword(s):  
Human Genome ◽  
Noncoding Rna ◽  
De Novo ◽  
Systematic Investigation ◽  
Comparative Genomic ◽  
Protein Coding ◽  
Protein Coding Genes ◽  
Competing Endogenous Rnas ◽  
Intergenic Regions ◽  
The Relationship

AbstractBackgroundThe regulatory roles of long intergenic noncoding RNAs (lincRNAs) in humans have been revealed through the use of advanced sequencing technology. Recently, three possible scenarios of lincRNA origin have been proposed: de novo origination from intergenic regions, duplication from long noncoding RNA, and pseudogenization from protein. The first two scenarios are largely studied and supported, yet few studies focused on the evolution from pseudo genized protein-coding sequence to lincRNA. Due to the non-mutually exclusive nature that these three scenarios have, accompanied by the need of systematic investigation of lincRNA origination, we conduct a comparative genomics study to investigate the evolution of human lincRNAs.ResultsCombining with syntenic analysis and stringent Blastn e-value cutoff, we found that the majority of lincRNAs are aligned to the intergenic regions of other species. Interestingly, 193 human lincRNAs could have protein-coding orthologs in at least two of nine vertebrates. Transposable elements in these conserved regions in human genome are much less than expectation. Moreover, 19% of these lincRNAs have overlaps with or are close to pseudogenes in the human genome.ConclusionsWe suggest that a notable portion of lincRNAs could be derived from pseudogenized protein-coding genes. Furthermore, based on our computational analysis, we hypothesize that a subset of these lincRNAs could have potential to regulate their paralogs by functioning as competing endogenous RNAs. Our results provide evolutionary evidence of the relationship between human lincRNAs and protein-coding genes.

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