Testing new hypotheses on the evolution of sex-related chromosomes

Project Information

EvolSexChrom

Grant agreement ID: 832352

DOI

10.3030/832352

Project closed

EC signature date 4 June 2019

Start date 1 October 2019

End date 30 September 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 500 000,00

EU contribution

€ 2 500 000,00

Coordinated by

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
France

Periodic Reporting for period 4 - EvolSexChrom (Testing new hypotheses on the evolution of sex-related chromosomes)

Reporting period: 2024-04-01 to 2025-09-30

Summary of the context and overall objectives of the project

The sex chromosomes of plants and animals often contain large non-recombining regions due to a stepwise cessation of recombination generating “evolutionary strata” of genetic differentiation. This is the case for example for the XY chromosomes in mammals. The reasons for the extension of recombination suppression beyond sex-determining genes remained however unclear. Sexual antagonism, based on differences between males and females, has long been the prevailing hypothesis. However, decades of research have unearthed little evidence to support this hypothesis. The aims of this project are to assess whether chromosomes involved in sexual compatibility in systems lacking male and female functions can nevertheless display a stepwise suppression of recombination beyond mating-compatibility genes, and to explore hypotheses alternative to sexual antagonism to explain such stepwise extension, both experimentally and theoretically.
This project revealed many cases of evolutionary strata in organisms without sexual antagonism, in multiple distant lineages, by generating and analysing genomic data in fungi. We revealed multiple independent events of recombination suppression in the Microbotryum fungi, causing anther-smut disease, as well as in several distant lineages of Sordariales fungi, found in soil. This shows that other mechanisms than sexual antagonistic are able to generate evolutionary strata.
We showed, by mathematical modeling and simulations, that recombination suppression on sex chromosomes can expand because of evolutionary phenomena linked to the presence of recessive deleterious mutations in genomes. We developped two theoretical models with different mechanisms based on the fact that recessive deleterious mutations are sheltered by permanently heterozygous alleles such as in the Y chromosome or mating-type alleles. We thus developed a new theory of sex chromosome evolution to explain the stepwise extensions of recombination suppression on sex-like chromosomes. We validated two predictions of these models : i) that stepwise recombination suppression around mating-type loci in fungi should only occur in diploid-like lineages, and ii) a a sheltered load exist in mating-type chromosomes.
Leveraging on the dataset of dozens of independent events of recombination suppression in Microbotryum fungi, we have elucidated how fast sex chromosomes degenerate, in terms of accumulation of non-synonymous substitutions, non-optimal codon usage and transposable element accumulation.
This project thus used a combination of different approaches and biological systems to refine and test hypotheses to broaden the theory of sex-related chromosome evolution. The EvolSexChrom project challenges the current theory, opening up new avenues of research and creating a paradigm shift in the dynamic research field focusing on the evolution of sex-related chromosomes, relevant to diverse traits and organisms. Because degeneration of the non-recombining chromosomes can impact health and fertility, this can have medical and societal relevance beyond academic importance.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Using new high-quality genome assemblies, we have revealed more than 35 independent events of recombination suppression across the Microbotryum genus and the existence of stepwise recombination suppression on many fungal mating-type chromosomes from distant lineages, and also in plants and oomycetes. We have written two reviews showing that stepwise evolution of recombination suppression is prevalent around mating-type genes in fungi, and we have reviewed the possible evolutionary causes. We have generated and analysed genomic data showing that the size of the non-recombining region around the mating-type locus was variable within and among species in Sordariales fungi. We have generated and analysed genomic data showing that a very large non-recombining region was present around the mating-type locus in the oomycete Plasmopara viticola, causing the downy mildiew disease on grapes.
We also analysed several features of degeneration following recombination suppression, thanks to the unique system we had revealed in the project, with dozens of independent events of recombination suppression of different ages. We showed that transposable elements accumulate rapidly after the onset of recombination suppression, and then less rapidly, while non-synonymous substitutions accumulate linearly with time. In vitro experiments revealed the existence of a sheltered load in mating-type chromosomes in Sordariales, i.e. recessive deleterious mutations impacting mycelial growth. We also revealed that the mating-type genes themselves can degenerate and become non-functional.
We have developed two theoretical models that show that recombination suppression can extend stepwise around a permanently heterozygous allele for sheltering deleterious mutations ; the models have generated predictions that we have tested using genomic data. In particular, we have shown that recombination suppression was strongly associated with a diploid-like life cycle in fungi, as predicted by our models.
By investigating genomic regions around fungal mating-type loci, we discovered an unexpected supergene in Cryphonectria parasitica, the fungal pathogen responsible for the chestnut blight disease. This is a non-recombining inversion of 1 Mb that is maintained polymorphic and contains starships (fungal giant mobile transposable elements carrying genes potentially playing roles in adaptation).
Our work has led so far to 25 scientific publications, including in highly accessed journals (Science, Current Biol, Mol Biol Evol, Nature Comm) and I have organized an international conference. We have presented results at international conferences and seminars and performed outreach movies on the project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

In this project, we have shown that other mechanisms than sexual antagonism are able to generate evolutionary strata on sex-like chromosomes, using genomic data, experiments and theoretical modeling. We have generated predictions to test our model. Altogether, we have thereby generated a new theory for the evolution of sex chromosomes. We have also used comparative and population genomic approaches to test predictions, which yielded results consistent with our models. The EvolSexChrom project challenges the current wisdom, opening up new avenues of research and creating a paradigm shift in the dynamic research field focusing on the evolution of sex-like chromosomes, relevant to diverse traits and organisms.

The unexpected high numbers of independent recombination suppression events across the Microbotryum phylogeny allowed us to investigate the temporal dynamics of transposable elements with time since recombination suppression, which had never been done before. The unique life cycle of the fungi allowed validating some of the predictions using experiments.

By investigating genomic regions around fungal mating-type loci, we further discovered an unexpected huge supergene in Cryphonectria parasitica, the fungal pathogen responsible for the chestnut blight disease. This supergene is a non-recombining inversion of 1 Mb that is maintained polymorphic in invasive European populations and contains starships, i.e. fungal giant mobile transposable elements carrying genes potentially playing roles in adaptation. This suggests a major role of this supergene in the adaptation of the invasive devastating chestnut blight pathogen.

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