Research The aim of our research is to understand phenotypic evolution by studying the processes by which the genetic networks underlying development diverge. Our major experimental system is sexual differentiation in Drosophila melanogaster and related flies. Sexual differentiation is a powerful model system for studying the evolution of development because many aspects of sexual morphology, physiology and behavior differ between closely related species, thereby enabling high resolution comparative analysis. In recent work, we have studied the evolution of intersex, a key regulatory gene required for female differentiation. We have cloned homologs of intersex from invertebrates and vertebrates, and used transgenics to show that, unlike other sex-determination factors, the function of the Intersex protein is broadly conserved. Interestingly, mammalian Intersex has recently been shown to be a component of the Mediator transcriptional co-activation complex. Thus, it appears that a general transcription factor evolved a sex-specific role in the lineage leading to Drosophila.  We are also interested in the divergence of the downstream programs of sex-specific gene expression. We combine genome-wide analysis of sex-biased gene expression with functional assays across closely related species to identify cases of interesting regulatory evolution.  We
complement our experimental work with theoretical investigations into
the evolution of gene networks. A central question is how networks
achieve robustness against environmental and genetic variation, so that
development leads to reliable phenotypic outcomes. A crucial related
question is how this robustness then modulates phenotypic divergence
between species. Our work suggests that gene networks of sufficient
complexity have an inherent robustness that need not be the product of
natural selection for robustness per se. It also suggests that many
genes might act as “phenotypic capacitors,” normally buffering genetic
and environmental variation, but revealing this variation
phenotypically when their function is impaired.
We also plan to test ideas about phenotypic capacitance in flies, by using a quantitative genomics approach to identify genes involved in sexual differentiation that harbor allelic variation, and then to investigate how variation in these genes is buffered and how these genes contribute to phenotypic differences between species. Areas of Research/Interest Genomic, genetic and computational approaches to the evolution of development, with a focus on sexual differentiation in Drosophila
Publications
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We are testing the prediction that a large number of genes might be phenotypic capacitors by systematically screening the Saccharomyces cerevisiae
genome for single-gene deletions that increase phenotypic variation.
Yeast is an advantageous system for this work because of its wealth of
genetic and genomic resources, and because it lends itself to
high-throughput analyses.