Mechanisms and Evolutionary Significance of

il y a 3 semaines


Montpellier, France Université de MontpellierUMR5244-UMR5554 Temps plein

**Mechanisms and evolutionary significance of hyperploidy variations in blue mussel transmissible cancer**:

- Réf **ABG-123538**
- Sujet de Thèse- 30/04/2024- Financement de l'Union européenne- Université de Montpellier/UMR5244-UMR5554- Lieu de travail- MONTPELLIER - Occitanie - France- Intitulé du sujet- Mechanisms and evolutionary significance of hyperploidy variations in blue mussel transmissible cancer- Champs scientifiques- Biologie
- Mots clés- Cancer transmissible, Hyperploïdie, Duplication du Génome, Dynamiques Evolutives, Diversité Génétique, Moule bleue/Transmissible Cancer, Evolutionary Dynamics, Hyperploidy, Whole Genome Duplication, Genetic Diversity, blue mussel**Description du sujet**:

- Les cancers transmissibles sont des entités biologiques étonnantes qui se propagent d’un animal à un autre par le transfert direct de cellules cancéreuses, se comportant ainsi comme des formes de vie parasitaires. Ils sont rares chez les mammifères, n’ayant en effet été décrits à ce jour que chez le chien et le diable de Tasmanie, mais sont plus fréquents chez les bivalves marins où 8 émergences distinctes sont connues aujourd’hui comme celle affectant les moules bleues européennes et nommée MtrBTN2. Ces lignées cancéreuses transmissibles persistent plusieurs centaines voire milliers d’années dans les populations d’hôtes comme c’est le cas pour la tumeur vénérienne canine apparue il y a plus de 4000 ans et aujourd’hui présente dans le monde entier. Durant cette longue évolution, ces lignées clonales sont soumises à des événements mutationnels stochastiques qui introduisent des variations génétiques somatiques dans la population de cellules. Si certaines mutations confèrent un avantage sélectif la plupart des mutations qui s’accumulent lors de cette évolution clonale sont délétères. Ainsi une question se pose : par quels mécanismes ces cancers font-ils face à la dégénérescence clonale qui pourrait conduire à leur extinction et comment génèrent-ils une diversité génétique suffisante pour garantir leur persistance en l’absence de reproduction sexuée ?- Ce projet doctoral se propose de répondre à cette question en étudiant les mécanismes évolutifs qui opèrent dans le cancer transmissible MtrBTN2 des moules communes _Mytilus edulis_. MtrBTN2, comme tous les autres cancers transmissibles des bivalves, est hyperploïde. De plus, nous avons identifié des sous-lignées divergentes de MtrBTN2 qui présentent des niveaux de ploïdie différents et spécifiques. L'hypothèse que nous avançons est que l'hyperploïdie contribue à amplifier l'hétérogénéité clonale, favorise la redondance génétique et allège transitoirement la charge génétique.- Dans le cadre de ce projet de thèse, nous proposons de nous concentrer sur les sous-lignées de MtrBTN2 pour i) déterminer si le degré d'hyperploïdie influence la fitness des cancers transmissibles, ii) comprendre comment l'hyperploïdie est générée et iii) déterminer quel est le devenir des lignées hyperploïdes nouvellement évoluées en termes de réorganisation du génome et d’acquisition de nouvelles caractéristiques phénotypiques.- Ces résultats pourraient contribuer à la prédiction des trajectoires évolutives des cancers transmissibles mais aussi conventionnels.- Ce projet doctoral sera réalisé dans le cadre du projet HYPERCAN financé par l’ERC Starting Grant.- This doctoral project aims to answer this question by studying the evolutionary mechanisms at work in the transmissible cancer of the blue mussel Mytilus edulis MtrBTN2. In particular, MtrBTN2, like all other bivalve transmissible cancers, is hyperploid. In addition, we have identified divergent sub-lineages of MtrBTN2 that display different and specific levels of ploidy. Our hypothesis is that hyperploidy contributes to the amplification of clonal heterogeneity, promotes genetic redundancy and transiently alleviates the genetic burden.
- In this PhD project, we propose to focus on MtrBTN2 sub-lineages to i) determine whether the degree of hyperploidy influences the fitness of transmissible cancers, ii) understand how hyperploidy is generated and iii) determine what is the fate of newly evolved hyperploid lineages in terms of genome reorganization and acquisition of new phenotypic traits.
- These results could contribute to predicting the evolutionary trajectories of both transmissible and conventional cancers.
- This doctoral project will be carried out as part of the HYPERCAN project funded by the ERC Starting Grant.**Prise de fonction**:

- 01/11/2024**Nature du financement**:

- Financement de l'Union européenne**Précisions sur le financement**:

- ERC Starting Grant (HYPERCAN 101116945)**Présentation établissement et labo d'accueil**:

- Université de Montpellier/UMR5244-UMR5554Co-direction IHPE et ISEM.

IHPE développe des recherches intégratives sur les interactions entre les animaux, leurs


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