Comparative genomics of alpha satellite DNA and the evolution of centromeric DNA
Stage · Stage M2 · 6 mois Bac+5 / Master Laboratoire Structure et Snstabilité des Génomes · Paris (France)
Date de prise de poste : 6 janvier 2025
Mots-Clés
alpha satellite DNA, centromeres, long read DNA sequencing, genome annotation, sequence classification, Primates
Description
The centromeres of eukaryotic chromosomes are made up of tandemly repeated DNA sequences, also known as satellite DNA. Thousands of copies of monomers are found next to each other in a head to tail configuration. The best studied satellite DNA, which represents around 3% of the human genome, is called alpha satellite DNA and has a monomer length of 171/172 bp. Many families of diverged monomers can be distinguished that differ in their distribution along chromosomes. Their peculiar diversity and distribution are thought to result from various mechanisms (recombination, amplification, insertion of new sequences..) that have not been yet fully elucidated.
The recent publication of the first human T2T (Telomere to Telomere) chromosome sequences (Logsdon et al 2024) enables for the first time a complete description of those sequences in the human genome. One can observe many local organizational patterns (so-called higher order repeats) as well as symmetric and chronologically distributed layers around centromeres. The most distant (and most ancient) layers have been proposed to be shared with other primates such as Old World monkeys, consistent with a model where new sequences are inserted at the centromere core and push older ones towards chromosome arms.
Our team addresses the evolution of centromeric DNA, using cercopithecini, a clade of Old World monkeys, as a model (Cacheux et al 2016, Cacheux et al 2018, Haschka et al 2020). In the context of an ongoing thesis work, we have developped new tools for studying the linear distribution of monomers on long DNA sequences.
In this context, the main objectives of the internship will be to :
1) use our tools for analyzing the diversity and organizational patterns of human alpha satellite DNA and compare the results with the current description.
2) compare the diversity and organizational patterns of alpha satellite DNA found in some Old World monkeys with those in the human genome.
The outputs of this project will be an improved description of the human alpha satellitome as well as new insights into the evolutionary mechanisms of those sequences as well as their contribution to centromere function and heterochromatin assembly.
References:
Cacheux et al (2016) Diversity and distribution of alpha satellite DNA in the genome of an Old World monkey: Cercopithecus solatus. BMC Genomics 17:916.
Cacheux et al (2018) The Targeted Sequencing of Alpha Satellite DNA in Cercopithecus pogonias Provides New Insight into the Diversity and Dynamics of Centromeric Repeats in Old World monkeys. Genome Biol. Evol. 10, 1837-1851.
Haschka et al (2021) MNHN-Tree-Tools: a toolbox for tree inference using multi-scale clustering of a set of sequences. Bioinformatics 37, 3947-3949.
Logsdon et al (2024) The variation and evolution of complete human centromeres. Nature.
Candidature
Procédure : Envoyer par mail votre CV ainsi qu'une lettre de motivation à christophe.escude@mnhn.fr et loic.ponger@mnhn.fr
Date limite : 31 décembre 2024
Contacts
Christophe ESCUDE
chNOSPAMristophe.escude@mnhn.fr
Offre publiée le 17 septembre 2024, affichage jusqu'au 31 décembre 2024