Post-Doc: Development of a new method to study the distribution of the effect sizes of QTL

Summary

We offer a 2-years position, working as post-doctoral fellow to improve our ability to study the genetic architecture of complex traits, by developing a new method to study the distribution of the effect sizes of Quantitative Trait Loci (QTL). The job will be mostly computational, based on statistical modelling and development, as well as assessing the performance of the method using simulated data. The candidate will work for the École Pratique des Hautes Études (PSL University), joining Pierre de Villemereuil’s team, at the Institute for Systematics, Evolution, Biodiversity (ISYEB), located within theMuséum National d’Histoire Naturelle (MNHN) in Paris. This position is funded as part of the EvoGenArch ERC Starting Grant. The position starts on 2024-09-16.

Scientific context

Most traits of ecological and evolutionary relevance are complex traits, i.e. influenced by a large number of loci (named Quantitative Trait Loci, or QTL) in the genomes. The features of the QTL are often referred to as the genetic architecture of the trait. One of the most important collective feature to characterise such architecture is the distribution of the effect sizes (i.e. the phenotypic impact of replacing one allele for the other) of QTL. Current methods allowing for the study of such distribution of effect sizes make the same core assumption: all QTL are a subset of the genetic markers (generally SNPs) available in the genome. However, QTL should come in all possible variety of genetic variants. This distinction between markers and QTL is generally not problematic if the aim is to locate a region of interest in the genome, or perform genomic predictions. However, if the goal is to infer the distribution of effect sizes from an evolutionary perspective, this distinction between markers and QTL becomes highly important. Indeed, if many, or most, markers are only linked to causal QTL, then the amount of linkage disequilibrium between each QTL and the markers will distort the inferred distribution of effect sizes. If we want to have a chance to empirically test the evolutionary predictions from the theoretical models, it is thus necessary to develop new methods that are focused on the inference of the distribution of QTL. The aim of this post-doctoral project is thus to develop such a new method, using the relation between linkage disequilibrium among markers nearby a QTL and the trait variance each of them “explain”, which is linked to the effect size of the QTL.

Job description

The job will be mostly computational, heavily based on statistical modelling and development, as well as assessing the performance of the method using simulated data. Under the supervision of Pierre de Villemereuil, in remote collaboration with Olivier François et Bertrand Servin, the candidate will:

• Develop the statistical method (including implementation, either as a package or as a compiled software) to infer the distribution of the effect sizes of QTL, using phenotypic and genomic data on a set of individuals. As a first approach, the method will follow the principles described in the EvoGenArch project, but the candidate will be at full liberty to put forward original ideas relevant to the project aim.

• Test the performance of the method, compared to existing state-of-the-art methods that are not distinguishing between markers and QTL, using phenotypic and genomic data simulated according to a set of scenarios.

• Empirically test the relevance of the new method by re-analysing a published dataset.

Hosting lab & team

Pierre de Villemereuil’s research focuses on the genetics of adaptation, trying to understand how the levels of the genotype, phenotype and environment interacts to drive evolution in wild populations, notably in response to anthropic pressures. A combination of evolutionary ecology, quantitative genetics, population genomics and statistical modelling is necessary to unveil the patterns and processes of adaptation in the wild. The Institute for Systematics, Evolution, Biodiversity (ISYEB), located in the beautiful Jardin des Plantes of the Muséum National d’Histoire Naturelle in Paris,is one of the largest labs studying evolution in the city. ISYEB hosts worldwide leading science in evolution, systematics, phylogeny, genomics and ecology.