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Le Targa, L.

Publications and source records attributed to Le Targa, L..

2 recordsLinked to original sources

Five-year (2017-2022) evolutionary dynamics of human coronavirus OC43 in southern France based on whole genome next-generation sequencing

HCoV-OC43 genomes and their evolution are scarcely studied worldwide and in France with only 361 genomes available as of October 2023. Here we implemented an in-house PCR amplification system to obtain retrospectively by next-generation sequencing then analyze HCoV-OC43 genomes for infections diagnosed with this virus in southern France between 02/2017 and 10/2022. Multiplex PCR amplification using a set of in-house primers designed using the Gemi software was carried out on residues of HCoV-OC43 RNA-positive nasopharyngeal samples, before next-generation sequencing (NGS) using Illumina technology on a NovaSeq 6000 instrument. HCoV-OC43 genome assembly, bioinformatic analyses, and phylogeny reconstruction were then carried out using CLC Genomics, Mafft, BioEdit, Nextstrain, Nextclade, MEGA, iTOL and RDP4 softwares. A total of 34 PCR primer pairs were designed for amplification then NGS of HCoV-OC43 genomes. A total of 185 genomes were obtained, 17, 79 and 89 belonging to genotypes G, J and K, respectively. These three genotypes circulated exclusively or co-circulated according to the year. A total of 303, 940, and 1,300 amino acid substitutions were detected in genotype G, J and K, respectively, compared with reference genomes of the same genotype dating back to 2017-2018. Possible recombinations were detected for 10 HCoV-OC43 genomes classified in genotypes K or J. Overall, the present study more than doubled the set of HCoV-OC43 genomes available worldwide for the 2017-2022 period, and contributed to the monitoring of the HCoV-OC43 evolutionary dynamics.

microbiology↗

Insights into RAG evolution from the identification of "missing link" family A RAGL transposons

A series of "molecular domestication" events are thought to have converted an invertebrate RAG-like (RAGL) transposase into the RAG1-RAG2 (RAG) recombinase, a critical enzyme for adaptive immunity in jawed vertebrates. The timing and order of these events is not well understood, in part because of a dearth of information regarding the invertebrate RAGL-A transposon family. In contrast to the abundant and divergent RAGL-B transposon family, RAGL-A most closely resembles RAG and is represented by a single orphan RAG1-like (RAG1L) gene in the genome of the hemichordate Ptychodera flava (PflRAG1L-A). Here, we provide evidence for the existence of complete RAGL-A transposons in the genomes of P. flava and several echinoderms. The predicted RAG1L-A and RAG2L-A proteins encoded by these transposons intermingle sequence features of jawed vertebrate RAG and RAGL-B transposases, leading to a prediction of DNA binding, catalytic, and transposition activities that are a hybrid of RAG and RAGL-B. Similarly, the terminal inverted repeats (TIRs) of the RAGL-A transposons combine features of both RAGL-B transposon TIRs and RAG recombination signal sequences. Unlike all previously described RAG2L proteins, PflRAG2L-A and echinoderm RAG2L-A contain an acidic hinge region, which we demonstrate is capable of efficiently inhibiting RAG-mediated transposition. Our findings provide evidence for a critical intermediate in RAG evolution and argue that certain adaptations thought to be specific to jawed vertebrates (e.g., the RAG2 acidic hinge) actually arose in invertebrates, thereby focusing attention on other adaptations as the pivotal steps in the completion of RAG domestication in jawed vertebrates.

evolutionary biology↗