Mots-Clés

Genome assembly Comparative genomics Soma/germline differentiation Evolution

Description

Context

Some species systematically eliminate parts of their genome in somatic cells, in a process called programmed-DNA elimination (PDE). The germline cells by contrast maintain an intact genome (Figure here: https://www.ens-lyon.fr/LBMC/offres/offres-de-stage/2023_internship_delattre?lang=en). Although PDE has emerged multiple times throughout evolution in animals, we still don’t know how the genome is scanned and excised at specific locations, or what PDE’s ultimate function is (1). We fortuitously discovered PDE in the free-living nematode worms Mesorhabitis (2, 3). In contrast to the other animal species so far described, Mesorhabditis are genetically tractable,offering a unique opportunity to finally understand the mechanism, role and evolution of PDE.

Proposed work

- Using new 3rd generation data (PacBio HiFi; Nanopore; + Hi-C for scaffolding) to separately assemble the somatic and germline genomes of multiple Mesorhabditis species.

- Using these genomes, testing how PDE breakpoints are specified and characterising the eliminated regions in detail (eliminated genes, transposable elements, satellite repeats...)

- Depending on the time available, performing computational searches for the molecular machinery responsible for PDE; and/or probing how PDE evolved in this genus

Prior experience

The successful candidate should be familiar with the basics of genome assembly and molecular evolution and be comfortable with bioinformatic scripting (some or all of python, R, shell). Prior experience in genomic bioinformatics is also a clear plus (genome assembly & annotation, comparative genomics, read mapping & variant calling). The ideal candidate should also be highly curious about biology – in particular genome biology and evolution.

Learning Objectives

Handling 3rd generation (PacBio, Nanopore) and Hi-C sequencing data; genome assembly & annotation; bioinformatic scripting; working in a biology-focussed environment; testing evolutionary hypotheses. Depending on the candidate we can also explore lower-level programming (C, C++, Rust), test-driven development and statistics.

References 

1. J. Wang, R. E. Davis, Programmed DNA elimination in multicellular organisms. Curr. Opin. Genet. Dev. 27, 26–34 (2014).

2. C. Rey, C. Launay, E. Wenger, M. Delattre, bioRxiv, in press, doi:10.1101/2022.03.19.484980.

3. M. Grosmaire, C. Launay, M. Siegwald, T. Brugière, L. Estrada-Virrueta, D. Berger, C. Burny, L. Modolo, M. Blaxter, P. Meister, M.-A. Félix, P.-H. Gouyon, M. Delattre, Males as somatic investment in a parthenogenetic nematode. Science. 363, 1210–1213 (2019).