Biology subjects

Le Meur, A.

Publications and source records attributed to Le Meur, A..

4 recordsLinked to original sources

bioRxiv2025

Ancestry, admixture, and pathogens in contemporaneous Neolithic farmers and foragers on the Island of Gotland

Two archaeological cultural complexes coexisted on Gotland for over 500 years, between [~]3300 and 2800 calBCE, i.e. the Neolithic Funnelbeaker culture (FBC), and the Pitted ware culture (PWC). The ancestry of the FBC farmers and PWC marine foragers largely aligns with European Neolithic Farmers and European Mesolithic foragers, respectively, but the direct interactions between the groups on Gotland is not understood. We present a Middle Neolithic (MN) high-coverage genome and a Late Neolithic (LN) low-coverage genome from the Ansarve FBC dolmen. We investigate ancestry, admixture, and pathogens among these MN farmers (n =6), foragers (n=19), and a LN individual. We find that recent gene-flow between farmers and foragers could have taken place, although most gene-flow happened prior to their coexistence on the island. We also find evidence of different Yersinia pestis strains in the three cultural groups, showing that the pestis was widespread among groups with different subsistence strategies.

genomics↗

bioRxiv2025

Improving the benchmark of variant calling in clonal bacteria using more realistic in silico genomes, the case of Mycobacterium tuberculosis

The democratisation of Whole Genome Sequencing data in bacterial genomics requires the benchmarking of associated analytical methodologies such as reference-based variant calling. Current variant calling benchmarks rely either on de novo assembled natural genomes, for which true variants are inferred using a genome aligner, or on genomes evolved in silico by incorporating short variants on reference genomes. We introduce Maketube, a method for evolving realistic genomes of the Mycobacterium tuberculosis complex with the full diversity of variants verified in natural isolates, and describe benchmarking results using Maketube-evolved genomes. We document that Maketube-evolved genomes satisfyingly mimic Mtbc complex genomes. Using Maketube-evolved genomes, we show that genome aligners miss up to 7.5% of the variants, which implies that benchmarkings with natural de novo assembled genomes are biased. Second, we show that recall of popular variant calling pipelines MTBseq, TB-Profiler, and our in-house genomic pipeline genotube, was overestimated by 1 to 10% in benchmarkings relying on simplistic in silico-evolved genomes, and that slight but significant differences in performance exist between pipelines. Finally, we provide evidence that variants are missed in duplicated regions and in regions flanking sequences absent in the reference (displaced insertion sequences or sequences deleted during the evolution of the reference). Altogether, realistic in silico-evolved genomes such as Maketube-derived ones are precious tools for reliable genomic tools benchmarking. We provide new evidence that structural variants interfere with variant-calling, both because of the additional sequences they contain, but also because of misalignments around insertions.

bioinformatics↗

bioRxiv2025

Genome wide analyses reveal the role of mutator phenotypes in the emergence of drug resistance in Mycobacterium tuberculosis

Antimicrobial combination therapy is widely used to combat Mycobacterium tuberculosis (Mtb), yet resistance rates continue to rise. Mutator strains, with defects in DNA repair genes, are a known source of resistance in other bacterial infections, but their global role in Mtb remains unclear. Here, we provide a comprehensive overview of the contribution of single nucleotide polymorphisms (SNPs) in DNA Repair, Replication, and Recombination (3R) genes to resistance in Mtb. Through large-scale bioinformatics analysis of 53,589 whole-genomes, we identified 18 novel SNPs linked to genotypic drug resistance in 3R genes, covering 12.5% of clinical isolates/strains with available genome sequences. Notably, a number of the detected SNPs were positively selected during Mtb evolution. Experimental mutation frequency tests further indicated functional defects of these sequence variants in key DNA repair pathways. Our findings indicate that the role of mutability in 3R genes plays a significant role in Mtb resistance at the global level.

evolutionary biology↗

bioRxiv2022

Mycobacterium tuberculosis genetic features associated with pulmonary tuberculosis severity

Mycobacterium tuberculosis (Mtb) infections result in a wide spectrum of clinical presentations but without proven Mtb genetic determinants. Herein, 234 pulmonary tuberculosis (TB) patients were stratified according to TB disease severity and Mtb genetic features were explored using whole genome sequencing, including heterologous single nucleotide polymorphism (SNP) calling to explore micro-diversity. Clinical isolates from patients with mild TB carried mutations in genes associated with host-pathogen interaction, while those from patients with moderate/severe TB carried mutations associated with regulatory mechanisms. Genome-wide association study identified a SNP in the promoter of the gene coding for the virulence regulator EspR associated with moderate/severe disease. Structural equation modelling and model comparisons indicated that TB severity was associated with the detection of Mtb micro-diversity within clinical isolates and to the espR SNP. Taken together, these results provide a new insight to better understand TB pathophysiology and could provide new prognosis tool for pulmonary TB severity.

microbiology↗