Biology subjects

Grandchamp, A.

Publications and source records attributed to Grandchamp, A..

11 recordsLinked to original sources

bioRxiv2025

Detect de novo expressed ORFs in transcriptomes withDESwoMAN

De novo gene emergence refers to the process by which new genes arise from mutations in previously non-coding genomic regions. Prior to becoming fixed in a species, newly expressed open reading frames (neORFs) undergo significant turnover within their species of origin. Investigating these early stages of de novo gene emergence is essential for understanding the mechanisms that enable gene formation from scratch. No software currently exists that can identify and characterise novel, unannotated open reading frames from a transcriptome, and analyse their mutations and fixation patterns within or across species. To address this gap, we introduce DESwoMAN (De novo Emergence Study With Outgroup MutAtioNs), a software tool designed to: (1) detect neORFs in transcriptomes, (2) filter neORFs with no homology to outgroup genes, and (3) search for syntenic sequences homologous to neORFs in outgroup genomes (and optionally transcriptomes) and analyse mutations in coding features between these sequences. We applied DESwoMAN with two different strategies to three setups, using twice human and once fruit fly as query species. Our results highlight the tools capabilities and demonstrate its potential for elucidating the early stages of de novo gene emergence. DESwoMAN is available at https://github.com/AnnaGrBio/DESWOMAN. It is implemented in Python3 and comes with a docker image on DockerHub for easy installation and execution including all (non-Python) dependencies.

bioinformatics↗

bioRxiv2025

DeNoFo: a file format and toolkit for standardised, comparable de novo gene annotation

MotivationDe novo genes emerge from previously non-coding regions of the genome, challenging the traditional view that new genes primarily arise through duplication and adaptation of existing ones. Characterised by their rapid evolution and their novel structural properties or functional roles, de novo genes represent a young area of research. Therefore, the field currently lacks established standards and methodologies, leading to inconsistent terminology and challenges in comparing and reproducing results. ResultsThis work presents a standardised annotation format to document the methodology of de novo gene datasets in a reproducible way. We developed DeNoFo, a toolkit to provide easy access to this format that simplifies annotation of datasets and facilitates comparison across studies. Unifying the different protocols and methods in one standardised format, while providing integration into established file formats, such as fasta or gff, ensures comparability of studies and advances new insights in this rapidly evolving field. Availability and ImplementationDeNoFo is available through the official Python Package Index (PyPI) and at https://github.com/EDohmen/denofo. All tools have a graphical user interface and a command line interface. The toolkit is implemented in Python3, available for all major platforms and installable with pip and uv.

bioinformatics↗

bioRxiv2025

Convergent Evolutionary Traces of Genomic Innovations and Depletions in Socially Parasitic Ants

Parasitism, a common strategy across life, often involves genomic reduction. Socially parasitic "slavemaking" ants provide an excellent model to study the evolution of this lifestyle. Here, we compared the genomes of four closely related, independently evolved parasite-host pairs and their outgroups to identify convergent patterns. While genome size and gene numbers remain relatively stable, parasites show increased positive and relaxed selection, more putative de novo genes which have recently emerged from previously non-coding regions, and a significant loss of chemical receptors, particularly those associated with the evolution of sociality. Hosts, however, retain many duplicated genes. Gene co-expression networks associated with nest-defence in hosts are rather conserved, while the network structure of raiding parasites is much more variable and reflects the independent evolutionary origin of social parasitism. Our findings suggest that while hosts primarily rely on existing molecular mechanisms for defence, parasite genome evolution is characterised by extensive, convergent gene loss, innovation, and network rewiring.

evolutionary biology↗

bioRxiv2024

DE Novo emerged gene SEarch in Eukaryotes with DENSE

The discovery of de novo emerged genes, originating from previously noncoding DNA regions, challenges traditional views of species evolution. Indeed, the hypothesis of neutrally evolving sequences giving rise to functional proteins is highly unlikely. This conundrum has sparked numerous studies to quantify and characterize these genes, aiming to understand their functional roles and contributions to genome evolution. Yet, no fully automated pipeline for their identification is available. Therefore, we introduce DENSE (DE Novo emerged gene Search), an automated Nextflow pipeline based on two distinct steps: detection of Taxonomically Restricted Genes (TRGs) through phylostratigraphy, and filtering of TRGs for de novo emerged genes via genome comparisons and synteny search. DENSE is available as a user-friendly command-line tool, while the second step is accessible through a web server upon providing a list of TRGs. Highly flexible, DENSE provides various strategy and parameter combinations, enabling users to adapt to specific configurations or define their own strategy through a rational framework, facilitating protocol communication, and study interoperability. We apply DENSE to seven model organisms, exploring the impact of its strategies and parameters on de novo gene predictions. This thorough analysis across species with different evolutionary rates reveals useful metrics for users to define input datasets, identify favorable/unfavorable conditions for de novo gene detection, and control potential biases in genome annotations. Additionally, predictions made for the seven model organisms are compiled into a requestable database, that we hope will serve as a reference for de novo emerged gene lists generated with specific criteria combinations. Significance StatementThe identification and classification of de novo genes, which originate from noncoding regions of DNA, remain an ongoing challenge in genomics research. While various approaches have been employed for their identification, the lack of a standardized protocol has resulted in varying lists of de novo genes across studies. This study introduces a novel tool: DENSE, that formalizes the common practices used in the field into a comprehensive and automated pipeline. DENSE streamlines the identification of taxonomically restricted genes, homology searches, and synteny analysis. This standardized methodology aims to enhance the accuracy and reliability of de novo gene identification, fostering a deeper understanding of the evolutionary mechanisms that drive gene birth and shape the genetic diversity of organisms.

genomics↗

bioRxiv2023

DNA Transposons favour de novo transcript emergence through enrichment of transcription factor binding motifs

De novo genes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORFs emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome. In this study we searched for de novo transcripts by using newly assembled genomes and transcriptomes of seven inbred lines of Drosophila melanogaster, originating from six European and one African population. This setup allowed us to detect line specific de novo transcripts, and compare them to their homologous non-transcribed regions in other lines, as well as genic and intergenic control sequences. We studied the association with transposable elements and the enrichment of transcription factor motifs upstream of de novo emerged transcripts and compared them with regulatory elements. We found that de novo transcripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with high CpG islands and regions of TEs activity. Moreover, upstream regions of de novo transcripts are highly enriched with regulatory motifs. Such motifs abound in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstream de novo transcripts than upstream their non-transcribed homologs. Overall, our study demonstrates that TEs insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.

genomics↗

bioRxiv2023

How antisense transcripts can evolve to encode novel proteins

Protein coding features can emerge de novo in non coding transcripts, resulting in emer- gence of new protein coding genes. Studies across many species show that a large frac- tion large fraction of evolutionarily novel non-coding RNAs have an antisense overlap with protein coding genes. The open reading frames (ORFs) in these antisense RNAs could also overlap with existing ORFs. In this study, we investigate how the evolution an ORF could be constrained by its overlap with an existing ORF in three different read- ing frames. Using a combination of mathematical modeling and genome/transcriptome data analysis in two different model organisms, we show that antisense overlap can increase the likelihood of ORF emergence and reduce the likelihood of ORF loss, es- pecially in one of the three reading frames. In addition to rationalising the repeatedly reported prevalence of de novo emerged genes in antisense transcripts, our work also provides a generic modeling and an analytical framework that can be used to under- stand evolution of antisense genes.

evolutionary biology↗

bioRxiv2023

High turnover of de novo transcripts in Drosophila melanogaster

Most of the transcribed eukaryotic genomes are composed of non-coding transcripts. Among these transcripts, some are newly transcribed when compared to outgroups and are referred to as de novo transcripts. De novo transcripts have been shown to play a major role in de novo gene emergence. However, little is known about the rates at which de novo transcripts are gained and lost in individuals of the same species. Here, we address this gap and estimate for the first time the de novo transcript turnover rate. We use DNA long reads and RNA short reads from seven samples of inbred individuals of Drosophila melanogaster to detect de novo transcripts that are (transiently) gained on a short evolutionary time scale. Overall, each sampled individual contains between 2,320 and 2,809 unspliced de novo transcripts with most of them being sample specific. We estimate that around 0.15 transcripts are gained per year, and that each gained transcript is lost at a rate around 5x10-5 per year. This high turnover of transcripts suggests frequent exploration of new genomic sequences within species. These rates provide first empirical estimates to better predict and comprehend the process of de novo gene birth.

genomics↗

bioRxiv2022

Population genomics reveals mechanisms and dynamics of de novo proto-gene emergence in Drosophila melanogaster

Scientific AbstractNovel genes are essential for evolutionary innovations and differ substantially even between closely related species. Recently, multiple studies across many taxa have suggested that some novel genes arise de novo, i.e. from previously non-coding DNA. In order to characterise the underlying mutations that allowed de novo gene emergence and their order of occurrence, homologous regions must be detected within non-coding sequences in closely related sister genomes. So far, most studies do not detect non-coding homologs of de novo genes due to inconsistent data and long evolutionary distances separating genomes. Here we overcome these issues by searching for proto-genes, the not-yet fixed precursors of de novo genes that emerged within a single species. We sequenced and assembled genomes with long-read technology and the corresponding transcriptomes from inbred lines of Drosophila melanogaster, derived from seven geographically diverse populations. We found line-specific proto-genes in abundance but few proto-genes shared by lines, suggesting a rapid turnover. Gain and loss of transcription is more frequent than the creation of Open Reading Frames (ORFs), e.g. by forming new START- and STOP-codons. Consequently, the gain of ORFs becomes rate limiting and is frequently the initial step in proto-gene emergence. Furthermore, Transposable Elements (TEs) are major drivers for intra genomic duplications of proto-genes, yet TE insertions are less important for the emergence of proto-genes. However, highly mutable genomic regions around TEs provide new features that enable gene birth. In conclusion, proto-genes have a high birth-death rate, are rapidly purged, but surviving proto-genes spread neutrally through populations and within genomes.

genomics↗

bioRxiv2022

New genomic signals underlying the emergence of human proto-genes

De novo genes are novel genes which emerge from non-coding DNA. Until now, little is known about de novo genes properties, correlated to their age and mechanisms of emergence. In this study, we investigate four properties: introns, upstream regulatory motifs, 5 UTRs and protein domains, in 23135 human proto-genes. We found that proto-genes contain introns, whose number and position correlates with the genomic position of proto-gene emergence. The origin of these introns is debated, as our result suggest that 41% proto-genes might have captured existing introns, as well as the fact that 13.7% of them do not splice the ORF. We show that proto-genes which emerged via overprinting tend to be more enriched in core promotor motifs, while intergenic and intronic ones are more enriched in enhancers, even if the motif TATA is most expressed upstream these genes. Intergenic and intronic 5 UTRs of protogenes have a lower potential to stabilise mRNA structures than exonic proto-genes and established human genes. Finally, we confirm that proto-genes gain new putative domains with age. Overall, we find that regulatory motifs inducing transcription and translation of previously non-coding sequences may facilitate proto-gene emergence. Our paper demonstrates that introns, 5UTRs, and domains have specific properties in proto-genes. We also show the importance of studying proto-genes in relation to their genomic position, as it strongly impacts these properties.

genomics↗

bioRxiv2021

A putative de novo evolved gene required for spermatid chromatin condensation in Drosophila melanogaster

Comparative genomics has enabled the identification of genes that potentially evolved de novo from non-coding sequences. Many such genes are expressed in male reproductive tissues, but their functions remain poorly understood. To address this, we conducted a functional genetic screen of over 40 putative de novo genes with testis-enriched expression in Drosophila melanogaster and identified one gene, atlas, required for male fertility. Detailed genetic and cytological analyses showed that atlas is required for proper chromatin condensation during the final stages of spermatogenesis. Atlas protein is expressed in spermatid nuclei and facilitates the transition from histone- to protamine-based chromatin packaging. Complementary evolutionary analyses revealed the complex evolutionary history of atlas. The protein-coding portion of the gene likely arose at the base of the Drosophila genus on the X chromosome but was unlikely to be essential, as it was then lost in several independent lineages. Within the last [~]15 million years, however, the gene moved to an autosome, where it fused with a conserved non-coding RNA and evolved a non-redundant role in male fertility. Altogether, this study provides insight into the integration of novel genes into biological processes, the links between genomic innovation and functional evolution, and the genetic control of a fundamental developmental process, gametogenesis. Author SummaryGenomes are in flux, as genes are constantly added and lost throughout evolution. New genes were once thought to arise almost exclusively via the modification or duplication of existing genes. Recently, however, interest has grown in alternative modes of new gene origination, such as de novo evolution from genetic material that previously did not encode proteins. Many de novo genes are expressed in male reproductive tissues, but their significance for fertility is not well understood. We screened likely de novo genes expressed in the Drosophila testis for reproductive roles and found one gene, atlas, essential for male fertility. We leveraged genetic and cell biological experiments to investigate roles for Atlas protein in reproduction and found that it is required during sperm development for proper packaging of DNA in the sperm nucleus. Evolutionary analyses of this gene revealed a complicated history, including loss in some lineages, movement between chromosomes, and fusion with a non-protein-coding gene. Studying both the functions and evolutionary histories of new proteins illustrates how they might evolve critical roles in biological processes despite their relative novelty. Furthermore, the study of atlas identifies an essential genetic player in the fly testis, an important model system for understanding how gametes are produced.

genetics↗

bioRxiv2021

Genes encoding teleost orthologs of human haplo-insufficient and monoallelic genes remain in duplicate more frequently than the whole genome

Gene dosage is important is an important issue both in cell and evolutionary biology. Most genes are present in two copies in eukaryotic cells. The first outstanding exception is monoallelic gene expression (MA) that concerns genes localized on the X chromosome or in regions undergoing parental imprinting in eutherians, and many other genes scattered throughout the genome. The second exception concerns haploinsufficiency (HI), responsible for the fact that a single functional copy of a gene in a diploid organism is insufficient to ensure a normal biological function. One of the most important mechanisms ensuring functional innovation during evolution is Whole genome duplication (WGD). In addition to the two WGDs that have occurred in vertebrate genomes, the teleost genomes underwent an additional WGD, after their divergence from tetrapod. In the present work, we have studied on 57 teleost species whether the orthologs of human MA or HI genes remain more frequently in duplicates or returned more frequently in singleton than the rest of the genome. Our results show that the teleost orthologs of HI human genes remained more frequently in duplicate than the rest of the genome in all the teleost species studied. No signal was observed for the orthologs of genes localized on the human X chromosome or subjected to parental imprinting. Surprisingly, the teleost orthologs of the other human MA genes remained in duplicate more frequently than the rest of the genome for most teleost species. These results suggest that the teleost orthologs of MA and HI human genes also undergo selective pressures either related to absolute protein amounts and/or of dosage balance issues. However, these constraints seem to be different for MA genes in teleost in comparison with human genomes.

evolutionary biology↗