Our research focuses on understanding (a) the genetic basis of between-individual variation in complex traits and (b) how such complex genetic architectures, instead of being static properties of a trait, get re-shaped when populations are exposed to different environments (genotype-by-environment interactions or GxE). In addition, we are particularly interested in (c) understanding how phenotypic robustness is regulated in such traits. That is, we aim to understand not only why individuals in a population look different from each other, but also why some individuals are more vulnerable than others when exposed to perturbations like stressful or new environments.
To explore these questions within the context of natural genetic variation, we use wild-derived outbred Drosophila melanogaster populations as model system. We integrate experimental and analytical tools across the fields of quantitative and population genetics, molecular and computational biology, and use experimental evolution to generate and analyze large-scale genomics datasets.
Conceptually, our research tackles long-standing questions in evolutionary biology including the genotype-phenotype map and its context-dependent nature, and the (apparent) conflict between robustness and evolvability.
Genetic architecture of morphological variation within populations
A prime example of a complex trait that is highly evolvable and at the same time highly constrained, is the vertebrate skull. Such dichotomy makes it a perfect system to study the interplay between genetic and environmental factor in determining phenotypic differences between individuals. Using wild-derived and outbred populations of the house mouse (Mus musculus) as a model system, I ask: What is the genetic architecture of craniofacial shape and size? To what extent is such variation heritable? What are the individual loci associated with between-individual variation, and what is their functional relationship to the phenotype? To answer these and other questions, I combine 3D Geometric Morphometrics, genome-wide mapping (GWAS), and functional genomic approaches.
Genotype-by-Environment interactions and their role in the regulation of complex traits
We mostly think about complex traits as having a defined and static genetic architecture, however, genetic effects are indeed highly dynamic, being modulated by environmental conditions. As a result, individuals with different genotypes will have different responses to environmental challenges, being more or less robust to such perturbations. Given the strong fitness-related effects associated with dietary composition, I’ve focused on diet as the environmental context in which to ask: How do different diets modify the phenotypic landscape of a population? how is the genetic architecture of such traits modulated by diet? what is the genetic basis for robustness?
Using outbred Drosophila melanogaster as a model system, I explore GxE interactions regulating the transcriptional response to dietary conditions. For this I’ve collected thousands of individual transcriptomes (using the high-throughput and cost-effective RNAseq protocol we’ve developed – TM3’seq) and am currently assessing the perturbations in gene co-expression patterns due to dietary differences and their underlying genetic regulation (eQTLs, vQTL, and GxE_eQTLs).
Dietary composition has also been associated with lifespan variation in a wide range of organisms, from C. elegans to humans. To understand to what extent Genotype-by-Diet interactions underlie lifespan variation in the D. melanogaster, I’ve quantified allele frequency and gene expression changes across the lifetime of a outbred D. melanogaster population consisting on thousands in individuals. [watch out for the pre-print coming out soon!]