Dr Frederic Fyon

Personal profile

You can find more on my profile and research projects on: https://fredericfyon.github.io/Home/

 

Research interests

As a population geneticist and a theoretician, I use models to understand the evolution of genetic odditities. I have been mostly interested in various new forms of intragenomic conflict. Conflicts - contrarily to what we tend to imagine - are a tremendous source of creation. It is becoming increasingly clear that the genome is not an harmonious cooperative entity; on the contrary, it is a battlefield of selfish interests and counter-tactics. These oppositions have given it the complex organization we know today. Although genomic data is piling, we still lack evolutionary theories to understand much of it - and that's where I hope that my work brings significant contribution.

 

Selfish cis-regulatory elements compete for transcription

Gene expression is regulated by cis-regulators (enhancers, promoters), which are non-coding sequences located upstream of the gene they regulate, and whose role is to be bound by transcription factors (trans-regulators). Importantly, cis-regulators only regulate one gene copy located on the same chromosome, and not the homologous one.

During my phD, I showed that cis-regulatory polymorphism should not only be selected to optimize individuals. In addition, I demonstrated using population genetics equations and stochastic forward simulations that "stronger" cis-regulators manage to get associated with better genetic background by revealing their associatd gene copy to selection. This provides them with indirect benefits, and they manage to selfishly spread in populations, though it incurs various costs to the host individuals. We named the process Enhancer Runaway because it relies on relative enhancer strengths, such that new stronger enhancers should recurrently invade as long as enhancer strength can physically be increased.The process can be slowed down by stabilizing selection on expression levels, but compensatory mutations in other elements of the regulatory network can give enhancers the freedom to increase in strength while maintaining optimal expression levels. This process thus could explain for example why regulatory networks as a whole tend to diverge rapidly between diverging, closely related species.

Interestingly, I also showed that this same runaway process should lead to the haploidization of expression when recombination between gene loci is completely shut down - for example due to clonal reproduction. Indeed, in such a case, I showed that the same intragenomic conflict leads to one homologous gene copy to accumulate deleterious mutations and be under-expressed, while the other gets purged from deleterious mutations and accounts for an increasingly high proportion of gene expression. We dubbed that process Enhancer Divergence. Most importantly, we showed that this other process should take place in sex chromosomes once recombination is shut down, and leads automatically to the degeneration and under-expression of Y (or W) chromosomes. We thus provided with an alternative theory to explain such degeneration, one that does no rely on selective interference, and is thus applicable more broadly.

 

Evolution of Asexual Reproduction in Hybrids

Though it was originally thought that asexuals should easily invade sexual populations due to a number of short-term benefits, this vision has been considerably revised in recent years. It has been proven mathematically that sexuals should benefit from widespread genetic advantages, and it has also been suggested that it is not physiologically easy for a sexual species to turn asexual. As a result, the task now resides in understanding why and how asexuality has managed to evolved several independent times in a diversity of eukaryotic taxa. Because so many asexuals are hybrid species, one key to the answer might be found in hybridization. Some are arguing that this is merely the mechanistic result of genetic incompatibilities between the parental species - however, the failure to produce readily asexual hybrids in a number of cases including the Poeciliid fish Amazon Molly (Poecilia formosa) might indicate that there may be other reasons why asexuality would appear in hybrid species.

In my postdoctoral project at the Royal Holloway, under the supervision of Pr. Úbeda and in collaboration with Pr. Ingo Schlupp's team at the University of Oklahoma, I have built a population dynamics model of sexual and asexual hybrids competing for resources. I am showing that asexual mutants may gain a selective advantage against sexual wild-types under a number of conditions, among which that the hybrid males be sterile (which is often the case in hybrid species due to genetic incompatibilities between the parental species). When fertilization is limited because many matings occur with males that are sterile as a result of hybridization, asexual, fertilization-independent mutants gain a reproductive advantage and spread. Although this model focuses on the example of the gynogenetic (sperm-dependent parthenogenetic) Amazon Molly, it is really extendable to any asexual hybrid species.

 

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