Abstracts guest speakers - FOR 1078 Meeting 2013
Dissecting gene regulatory principles using Drosophila and human population genomics
Institute of Bioengineering
Swiss Federal Institute of Technology (EPFL)
The accurate control of molecular and cellular processes is fundamental to organismal development and homeostasis. DNA sequence variation has been associated with quantitative changes in several of these processes. Here, I will present two studies aiming to exploit this form of variation as a valuable resource to unravel gene regulatory mechanisms.
In the first part, I will discuss our efforts to generate a catalog of single-nucleotide, multi-nucleotide, and structural variants in Drosophila melanogaster Genetic Reference Panel inbred lines. We then used this variant catalog to provide insights into the regulatory architecture of gene expression variation in adult flies by mapping cis-expression quantitative trait loci (cis-eQTLs) for more than 2,000 genes. Indels comprise around 10% of all cis-eQTLs and show larger effects than SNP cis-eQTLs. In addition, we identified two-fold more gene associations in males as compared to females and found that most cis-eQTLs are sex-specific, revealing a partial decoupling of the genomic architecture between the sexes as well as the importance of genetic factors in mediating sex-biased gene expression.
In the second part, I will present our efforts to understand both DNA sequence-dependent and independent variation in DNA binding, chromatin state, and transcription, and their interplay in an allele-specific framework. Specifically, we generated genome-wide enrichment profiles of transcription factor binding, chromatin marks, and different measures of transcription in lymphoblastoid cell lines from 14 human samples and quantified inter-individual variability in these phenotypes. We find that different organizational layers of the genome show abundant allelic effects and strong allelic coordination between layers, with the genetic control of this coordination acting primarily through transcription factor binding. Our findings support the notion of transcription factors being the primary determinants of gene expression programs, with the overall chromatin state reflecting but not necessarily driving gene expression activity.top
Institute of Evolutionary Sciences
CNTS – University Montpellier 2
The population genomic literature has been so far dominated by a handful of model organisms in which the available genomic resources were concentrated. Next-generation sequencing (NGS) in principle offers the opportunity to investigate the molecular diversity of non-model species genome-wide in absence of any prior knowledge. The PopPhyl project takes a comparative approach to population genomics across animals. It aims at investigating the relationship between species biology and genome variation patterns based on RNA-seq data in >30 metazoan species (10 individuals each) and their outgroups, and de novo SNP and genotype calling. I will present the technical, theoretical and bioinformatic challenges that we have faced, illustrate the potential of the approach through the case study of the giant Galapagos tortoise, and present the first comparative results regarding the ecological and life-history determinants of species genetic diversity in metazoans (http://kimura.univ-montp2.fr/PopPhyl).
Wellcome Trust Centre for Human Genetics
The selective forces experienced by individuals within a species, for example those arising from environment and pathogens, are often spatially structured. Patterns of genetic variation observed within and between populations and species provide an opportunity to learn about such forces, though there are multiple challenges to rigorously testing the hypothesis of local adaptation or other selective regimes. I will discuss what we have learned from whole-genome sequencing studies about the structuring of human genetic variation, including evidence for local adaptation and long-term balancing selection since before the human-chimpanzee split. I will also discuss how longitudinal sampling of genetic variation from a species can be used to infer spatially-varying selection coefficients and how such approaches might be used to learn about the history of a species.top
Ecology & Evolution
University of Fribourg
In Daphnia, parthenogenetic reproduction alternates with sexual reproduction, and the sex is usually determined by the environment. However, some lines never produce males, and these non-male producing ("NMP") genotypes can only persist through phases of sexual reproduction if they co-occur with normal ("MP") genotypes that produce both males and females. The distinction between MP and NMP is genetically determined by a single chromosomal region carrying a dominant NMP allele and showing characteristics of a young sex chromosome. In particular, there is evidence for strong suppression of recombination in this region, which may favor the accumulation of further sex-specific loci. However, surprisingly, recombination in this region is also suppressed between the normal MP-chromosomes (analogous of Z-chromosomes in birds). Thus, contrary to the common assumption, recombination suppression may not necessarily evolve after the appearance of sex-determining mutations, but, rather, sex determining mutations may have an advantage if the happen to occur in a region in which recombination is already suppressed. In my talk I will give an overview of these results on recombination suppression, and show how the breeding system polymorphism can be exploited to answer questions about sex chromosome evolution and evolution of genetic sex determination in general.