The aim of our research is to understand phenotypic evolution by
studying the processes by which the genetic networks underlying
development diverge. Our lab uses two major experimental systems, as
well as computational modeling.
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One 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. |
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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. |
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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. |
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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, our
second major experimental system, is advantageous for this work because of its
wealth of genetic and genomic
resources, and because it lends itself to high-throughput analyses. 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. |