Biology subjects

Massip, F.

Publications and source records attributed to Massip, F..

9 recordsLinked to original sources

bioRxiv2026

Inferring evolutionary distances from whole prokaryotic genome alignments, accounting for among-locus substitution rate heterogeneity

Ever since the rise of next generation sequencing technologies, the number of prokaryotic genomes in databases has increased tremendously. In order to leverage those vast quantities of data, an approach was previously introduced to estimate evolutionary divergences by modeling the genomic distances between substitutions in many whole genome alignments. However, this proof of concept study was conducted on the Enterobacterales clade only, such that its applicability to other clades remained to be established. In this study, we demonstrate the broad applicability of this method to a wider range of clades and to species with larger evolutionary divergences. We also show that relaxing a hypothesis on the substitution rate distribution, with a single additional free parameter, drastically improves both the estimation of evolutionary divergences and the quality of the inferred trees. We use simulations to show that our method can correctly recover the tree topology in cases where substitution rates evolve along the tree. Finally, our results also have theoretical implications for our understanding of substitution rate heterogeneity in genomes, since we found differences in the range of substitution rate distribution in our three examples Bacillales, Enterobacterales and Methanobacteriota whose causes remain to be identified.

evolutionary biology↗

bioRxiv2025

Reconstructing the network of horizontal gene exchange in bacteria to differentiate direct and indirect transfers

Horizontal gene transfer (HGT) plays a central role in bacterial evolution. Yet, its large-scale dynamics and underlying network structure remain poorly characterized. We present a theoretical framework that models HGT as a continuous stochastic process over a network of bacterial genera and analyze its genomic footprint via the distribution of exact sequence matches shared across taxa--the match length distribution (MLD). We show that different evolutionary regimes imprint distinct statistical signatures on the MLD: single episodic gene transfer events yield exponential distributions, while continuous sustained HGT processes lead to power-law tails. The power-law exponent is analytically linked to the topology of the transfer network, distinguishing between intraclade transfers and hub-mediated dissemination. Empirical MLDs derived from bacterial genomes recapitulate these predicted patterns. Moreover, we find that defining a genus-specific "transferability" parameter that governs pairwise HGT rates and incorporating a high-transferability hub accurately reproduces the observed data. Our approach provides a general framework for inferring hidden structure in genomic horizontal transfer processes, enabling quantitative analysis of microbial evolution.

genomics↗

bioRxiv2023

A point cloud segmentation framework for image-based spatial transcriptomics

Recent progress in image-based spatial RNA profiling enables to spatially resolve tens to hundreds of distinct RNA species with high spatial resolution. It hence presents new avenues for comprehending tissue organization. In this context, the ability to assign detected RNA transcripts to individual cells is crucial for downstream analyses, such as in-situ cell type calling. Yet, accurate cell segmentation can be challenging in tissue data, in particular in the absence of a high-quality membrane marker. To address this issue, we introduce ComSeg, a segmentation algorithm that operates directly on single RNA positions and that does not come with implicit or explicit priors on cell shape. ComSeg is thus applicable in complex tissues with arbitrary cell shapes. Through comprehensive evaluations on simulated datasets, we show that ComSeg outperforms existing state-of-the-art methods for in-situ single-cell RNA profiling and cell type calling. On experimental data, our method also demonstrates proficiency in estimating RNA profiles that align with established scRNA-seq datasets. Importantly, ComSeg exhibits a particular efficiency in handling complex tissue, positioning it as a valuable tool for the community.

bioinformatics↗

bioRxiv2023

An analytical derivation of the distribution of distances between heterozygous sites in diploid species to efficiently infer demographic history

Heterozygous sites are not uniformly distributed along a diploid genome. Rather, their density varies as a result of recombination events, and their local density reflects the time to the last common ancestor of the maternal and paternal copies of a genomic region. The distribution of the density of heterozygous sites therefore carries information about the history of the population size. Despite previous efforts, an exact derivation of the distribution of heterozygous sites is still lacking. As a consequence, the estimation of population size variation is difficult and requires several simplifying assumptions. Using a novel theoretical framework, we are able to derive an analytical formula for the distribution of distances between heterozygous sites. Our theory can account for arbitrary demographic histories, including bottlenecks. In the case of a constant population size the distribution follows a simple function and exhibits a power-law tail proportional to r with =-3, where r is the distance between heterozygous sites. This prediction is accurately validated when considering heterozygous sites in individuals of African descent. Other populations migrated out of Africa and underwent at least one bottleneck which left a distinct mark on their interval distribution between heterozygous sites, i.e., an overrepresentation of intervals between 10 and 100 kbp in length. Our analytical theory for non-constant population sizes reproduces this behavior and can be used to study historical changes in population size with high accuracy. The simplicity of our approach facilitates the analysis of demographic histories for diploid species, requiring only a single unphased genome.

genomics↗

bioRxiv2023

Modeling the mosaic structure of bacterial genomes to infer their evolutionary history

The timing and phylogeny of bacterial evolution is difficult to reconstruct because of a scarce fossil record, deep genomic divergences and complexities associated with molecular clocks. Studying bacterial evolutionary history using rich and rapidly accumulating genomic data requires accurate modeling of genome evolution, taking into account that different parts of bacterial genomes have different history. In particular, along the genome, different loci are subject to different selective pressure. In addition, some are horizontally transferred from one bacterium to another, resulting in a mosaic-like genome structure. An important technical aspect is that loci with high effective mutation rates can diverge beyond the aligner detection limit, biasing the genome-wide divergence estimate towards more conserved loci. Therefore, the genome-wide molecular clock cannot be directly applied to study bacterial evolutionary history. In this article, we propose a novel method to gain insight into bacterial evolution based on statistical properties of genomic sequences comparisons. The length distribution of the sequence matches is shaped by the effective mutation rates of different loci, by the horizontal transfers and by the aligner sensitivity. Based on these inputs we build a model and demonstrate that it accounts for the empirically observed distributions, taking the Enterobacteriaceae family as an example. Using the model and the empirical data we fit the evolutionary parameters: time divergences and horizontal transfer rates. Based on the estimated time divergences we build a time-calibrated phylogenetic tree, demonstrating the accuracy of the method and its ability to unravel vertical and horizontal transfers in bacterial genomes.

evolutionary biology↗

bioRxiv2022

Dimeric G-quadruplex motifs determine a large fraction of strong replication origins in vertebrates

Replication of vertebrate genomes is tightly regulated to ensure accurate duplication, but our understanding of the interplay between genetic and epigenetic factors in this regulation remains incomplete. Here, we investigated the involvement of three elements enriched at gene promoters and replication origins: guanine-rich motifs potentially forming G-quadruplexes (pG4s), nucleosome-free regions (NFRs), and the histone variant H2A.Z, in the firing of origins of replication in vertebrates. We show that two pG4s on the same DNA strand (dimeric pG4s) are sufficient to induce assembly of an efficient minimal replication origin without inducing transcription. Dimeric pG4s in replication origins trigger formation of an NFR next to precisely-positioned nucleosomes enriched in H2A.Z on this minimal origin and genome-wide. Thus, our data suggest a crucial role for dimeric pG4s in the organization and duplication of vertebrate genomes. It supports the hypothesis that a nucleosome close to an NFR is a shared signal for the formation of replication origins in eukaryotes.

genomics↗

bioRxiv2021

Locus specific epigenetic modalities of random allelic expression imbalance

Most autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression was not observed in ESCs, but when we assessed expression status in more than 200 clones of neuronal progenitor cells, we observed high frequencies of monoallelism. We uncovered unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up novel therapeutic perspectives.

molecular biology↗

bioRxiv2020

Long identical sequences found in multiple bacterial genomes reveal frequent and widespread exchange of genetic material between distant species.

Horizontal transfer of genomic elements is an essential force that shapes microbial genome evolution. Horizontal Gene Transfer (HGT) occurs via various mechanisms and has been studied in detail for a variety of systems. However, a coarse-grained, global picture of HGT in the microbial world is still missing. One reason is the difficulty to process large amounts of genomic microbial data to find and characterise HGT events, especially for highly distant organisms. Here, we exploit the fact that HGT between distant species creates long identical DNA sequences in genomes of distant species, which can be found efficiently using alignment-free methods. We analysed over 90 000 bacterial genomes and thus identified over 100 000 events of HGT. We further developed a mathematical model to analyse the statistical properties of those long exact matches and thus estimate the transfer rate between any pair of taxa. Our results demonstrate that long-distance gene exchange (across phyla) is very frequent, as more than 8% of the bacterial genomes analysed have been involved in at least one such event. Finally, we confirm that the function of the transferred sequences strongly impact the transfer rate, as we observe a 3.5 order of magnitude variation between the most and the least transferred categories. Overall, we provide a unique view of horizontal transfer across the bacterial tree of life, illuminating a fundamental process driving bacterial evolution.

bioinformatics↗

bioRxiv2018

Evolution of Replication Origins in Vertebrate Genomes: Rapid Turnover Despite Selective Constraints.

BackgroundThe replication programme of vertebrate genomes is driven by the chro-mosomal distribution and timing of activation of tens of thousands of replication origins. Genome-wide studies have shown the frequent association of origins with promoters and CpG islands, and their enrichment in G-quadruplex sequence motifs (G4). However, the genetic determinants driving their activity remain poorly understood. To gain insight on the functional constraints operating on replication origins and their spatial distribution, we conducted the first evolutionary comparison of genome-wide origins maps across vertebrates.\n\nResultsWe generated a high resolution genome-wide map of chicken replication origins (the first of a bird genome), and performed an extensive comparison with human and mouse maps. The analysis of intra-species polymorphism revealed a strong depletion of genetic diversity on an ~ 40 bp region centred on the replication initiation loci. Surprisingly, this depletion in genetic diversity was not linked to the presence of G4 motifs, nor to the association with promoters or CpG islands. In contrast, we also showed that origins experienced a rapid turnover during vertebrates evolution, since pairwise comparisons of origin maps revealed that only 4 to 24% of them were conserved between any two species.\n\nConclusionsThis study unravels the existence of a novel genetic determinant of replication origins, the precise functional role of which remains to be determined. Despite the importance of replication initiation activity for the fitness of organisms, the distribution of replication origins along vertebrate chromosomes is highly flexible.

evolutionary biology↗