Evolution of the genotype-phenotype relationship in natural population of yeast – EvoPheno

In the past 5 years, new generation sequencing technologies have emerged. These strategies allow the determination of the complete genome sequences of a large number of individuals. It is now possible to explore the genetic diversity within a species.
In addition, new methods were developed to study the variation of observable characteristics or traits. As an example, it is now possible to follow the growth rate of large collection of yeast isolates in a broad variety of conditions.
Datasets generated using these strategies will allow to have a global view of the impact of genetic diversity on the observable trait variation.

In our project, two major and unrelated results came out of the species-wide surveys we conducted. First, we have unveiled the multiplicity of the mechanisms involved in the reproductive isolation at the intraspecific level. They range from large-scale chromosomal rearrangements to genetic incompatibilities. Second, we have clearly shown that monogenic mutations can have a variable impact on a population. These deviations from the Mendelian expectation ranged from intermediate to high complexities illustrating the hidden complexity of a monogenic mutation across a natural population.

By using Saccharomyces cerevisiae as a model organism, we plan to have a better insight into the relation between genetic diversity and variation of traits of interest. Today, this relation is still unclear and difficult to study in human or other model organisms.

Selected publications

1. Hou J, Friedrich A, Gounot JS, Schacherer J. Comprehensive survey of condition specific reproductive isolation reveals genetic incompatibility in yeast. Nat Commun. 2015. 6: 7214.
2. Brion C, Pflieger D, Friedrich A, Schacherer J. Evolution of intraspecific transcriptomic landscapes in yeasts. Nucleic Acids Res. 2015. 43: 4558-68.
3. Friedrich A, Jung P, Reisser C, Fischer G, Schacherer J. Population genomics reveals chromosome-scale heterogeneous evolution in a protoploid yeast. Mol Biol Evol. 2015. 32: 184-92.
4. Freel KC, Friedrich A, Hou J, Schacherer J. Population genomic analysis reveals highly conserved mitochondrial genomes in the yeast species Lachancea thermotolerans. Genome Biol Evol. 2014. 6: 2586-2594.
5. Hou J, Friedrich A, de Montigny J, Schacherer J. Chromosomal rearrangements as a major mechanism in the onset of reproductive isolation in Saccharomyces cerevisiae. Current biology. 2014. 24: 1153-1159.
6. Bleykasten-Grosshans C, Friedrich A, Schacherer J. Genome-wide analysis of intraspecific transposon diversity in yeast. BMC Genomics. 2013. 14: 399.
7. Reisser C, Dick C, Kruglyak L, Botstein D, Schacherer J, Hess D. Genetic basis of ammonium toxicity resistance in a sake strain of yeast: a mendelian case. G3 (Bethesda). 2013. 3:733-740.
8. Friedrich A, Jung PP, Hou J, Neuvéglise C, Schacherer J. Comparative mitochondrial genomics within and among yeast species of the Lachancea genus. PLoS ONE. 2012. 7: e47834.
9. Jung PP, Friedrich A, Reisser C, Hou J, Schacherer J. Mitochondrial genome evolution in a single protoploid yeast species. G3 (Bethesda). 2012. 2: 1103-1111.

Identification of the genetic variation between individuals within a species is valuable to understanding the genetic basis of phenotypic differences and the patterns of molecular evolution. Therefore we sought to generate a comprehensive view of sequence polymorphism in S. cerevisiae. We generated a genomic map at the nucleotide level of a collection of 63 S. cerevisiae strains sampled from different ecological niches (beer, bread, vineyards, immunocompromised individuals, various fermentations and nature) and from locations on different continents. These results and the polymorphism resource we have generated lay the foundation for genome-wide association studies in yeast.
Our research proposal will obviously focus on the phenotypic characterization to determine their genetic basis. Based on this large collection of S. cerevisiae strains and a unique set of data, our ultimate aim will be to get a better insight into the general rules that govern the genotype-phenotype relationship within a species, using approaches based on new techniques such as deep sequencing and microfluidics. The goal is to combine high-throughput phenotyping, sequencing and computational methods to identify a large set of functional polymorphisms in yeast. Nevertheless proper integration of the multiple levels of information is without doubt the toughest challenge in genomic studies. For the purpose of technical and biological validation, we will initially focus experiments on a small set of well-defined phenotypes: reproductive isolation and multidrug resistance (ketoconazole, rhodamine 6G, cycloheximide for example). First, we will focus on quantitative measurement of the phenotypes. Second, we will be to map the genetic basis of them. Based on existing sequence data (complete and partial sequences of hemiascomycete genomes), we will also have the opportunity to evaluate DNA sequence variation and genome evolution.