CE02 - Terre vivante

Mito-Nuclear Interactions and Gyodioecy in ANimals – MINIGAN

Mitochondria that manipulate sex

We study cytoplasmic male sterility (CMS) in a freshwater snail. This species is normally hermaphroditic, however individuals lose the male function when they carry a particular type of mitochondria. This system is well-known and has been modelled in flowering plants, we discovered it for the first time in animals. The animal system authorizes many new experimental approaches to explore this example of genomic conflict over dex determination.

A unique model system to study genomic conflicts

MINIGAN is the first study of an animal example of cytoplasmic male sterility (CMS). This example will aloow us to observe in real time, how a set of genes in conflict evolve. The conflict here comes from the different modes of transmission of genomic compartments. The mitochondrial genome is transmitted only by the mother, while the nuclear genome is thransmitted by both male and female parents equally. As a consequence, mitochondrial genes have no interest in the aintenance of a male function; in a hermaphroditic individual they may even be selected to suppress the male function if this suppresion saves energy that can be re-invested into the female function. In this situation nuclear genes are selected to restore the male function, hence the conflict over sex determination. <br />To better understand how this conflict takes place, we must first explore the distribution of the different types of mitochondria (male-sterilizing of not) and their effects on sexual reproduction in natural populations. Then we will experimentally measure the joint effect of mitochondria and conflicting nuclear gene on male and femle reproduction, physiology, anatomy, behavior in the laboratory. We will set up a protocol to observe the evolution of both types of genes (mitochondrial and nuclear) over several generations. his direct approach of evolutionary dynamics will be compleed by an indirect approach. The latter will consist in observeing genomic consequences of historical presence and absence of CMS-bearing mitochondria in natural populations.

Our methodology combines sevral complementary levels of analysis of our biologica system.

- The first is fieldwork; we sample many natural populations, genotype and phenotype them in order to quantify the freuency and distribution of CMS-bearing mitochondria and the actual rate of phenotypic male sterility in the carriers.

- We use laboratory experments to make controlled crosses, measure life-history and fitness in standardized conditions, and maintain experimental populations over several generations (experimental evolution)

- Molecular techniques include genotyping by PCR on mitochondrial DNA, sequencing, transciptomics, re-sequencing of accessions from natural populations.

- bioinformatic treatment of omics data (genome assembly, genome scan)

- mathematical modelling will be made to understand and predict the evolutionary dynamics of our CMS system.

Our main result so far is the discovery of two mitochondrial types that induce male sterility. Both types are characterized by high rates of molecular evolution, due to an elevated mutation rate. For one of these types we have also show the existence of nuclear genes that antagonize the male-sterilizing effect (called restorers beaus they restore the hermaphroditic phenotype). Indeed, the male-sterile phenotype is present when the CMS mitochondria are associated with some types of nuclear background and absent with other backgrounds. We also demonstrated the existence of a female beefit to CMS, as individuas that lose the male function enjoy an increased female fertility. We have started to model the evolution of this type of CMS system.

Our study is still ongoing and many ongoing experiments will yield results that provide a better comprehension of cytoplasmic male sterility. This way we will better characterize the genetic nature of nuclear restorers of the male function, its specific or unspecific character with respect to the various CMS mitotypes, We have passed the first few generations of experimental evolution succesfully and this work will be continued to provide a detailed view of evolutionary dynamics of this system.
Finally, we will have to intensify even more our field approach to describe the distribution and stability of CMS mitotypes in natural populations.
This work will shed a new light on one of the most important known genomic conflicts in hermaphroditic orgaisms, but also on issues applicable to separate-sex orgabisms, including humans. Indeed in such organisms, mitochondrial mutations have been repeatedly involved in hereditary defects of male fertility.

This ongoing project is still to be published.

The concept of genetic conflict is one of the most important legacies of twentieth century evolutionary biology, and has now become, in the era of massive sequencing, a major foundation of our understanding of genome evolution. Genetic conflicts occur within organisms between different genes that maximize their transmission in different ways. A spectacular example is cytoplasmic male sterility (CMS), whereby maternally transmitted mitochondrial genes suppress the male function in hermaphrodites, to the detriment of nuclear genes. The result is a sexual polymorphism called gynodioecy, whereby hermaphrodites coexist with females in populations. CMS and gynodioecy have been well studied theoretically, and empirically in plants. They have become one of the textbook examples of genetic conflicts. However CMS has surprisingly never been described in animals. In addition, tests of the evolutionary theory of gynodioecy remained indirect, as the long generation time of most gynodioecious plants made it complicated to observe evolutionary dynamics over generations, in real time.

We recently discovered the first animal example of CMS in a hermaphroditic freshwater snail Physa acuta (Pa) and propose to use this species as a new model to study genetic conflicts. Capitilizing on the short generation time of this snail - easy to breed in the lab-, and on the preliminary data accumulated in the past two years, we propose a project that will not only open this field of evolutionary genetics to a new clade (animals), but also follow hitherto unexplored, exciting research avenues, such as experimental evolution. MINIGAN is organized along four axes / questions. (i) What is the geographical distribution of CMS and does it occur in specific environmental conditions? (ii) Is male sterility compensated by a female advantage, how and when is this advantage expressed ? (iii) Can we directly observe the co-evolutionary cycles of mitochondrial and nuclear genomes predicted by models, as a consequence of mtDNA suppressing male function while some nuclear genes restore it ? (iv) What is the genomic signature of gynodioecy ? How does CMS affect mitochondrial and nuclear genomes and transcriptomes?

We will rely on a variety of approaches already used in plant models including field sampling, PCR, intensive lab experiments, together with more innovative methods such as experimental evolution, genome scans, and transcriptomics. This project is ambitious, requiring long-term (2yr) experimental evolution and a de-novo assembly of the snail genome, and a large re-sequencing effort. This combination of various techniques results in a balanced mix of relatively low-risk and high-risk, high-gain approaches.

The diversity of methods also echoes the complementarity of competences present in the three different partners of the consortium and their respective scientific leaders. The project is coordinated by P. David in CEFE (Montpellier), broad-spectrum evolutionary biologist, quantitative and population geneticist, and specialist of animal mating systems with long experience with working with snails as model systems. A whole team, including a specialist of gynodioecy in plants, will assist him in the CEFE. Both E. Luquet and J. Romiguier (respectively leaders of the LEHNA partner in Lyon and ISEM partner in Montpellier) are talented young researchers who, together with their associated teams, will bring their knowledge in life-history evolution, transcriptomics and genomics. Collaboration will be facilitated by geographical proximity, and the succesful past collaborations between the partners on the snail model, already materialized by common publications and by the obtention of the preliminary results forming the basis of this project.

Gathering a well-integrated consortium of high-profile research teams with complementary skills, MINIGAN has the potential to shed a new light on the dynamics of CMS, and more generally on genetic conflicts.

Project coordinator

Monsieur Patrice DAVID (Centre d'Ecologie Fonctionnelle et Evolutive)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

CEFE Centre d'Ecologie Fonctionnelle et Evolutive
LEHNA LABORATOIRE D'ECOLOGIE DES HYDROSYSTEMES NATURELS ANTHROPISES
ISEM Institut des Sciences de l'Evolution de Montpellier

Help of the ANR 605,639 euros
Beginning and duration of the scientific project: January 2020 - 42 Months

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