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Assistant Professor of Biology
Ph.D. 1998, (Biology), Harvard University; B.S. 1993 (Biology), Brown University.
Office Address:
| New York University |
| Center for Genomics and Systems Biology |
| Department of Biology |
| 1009 Silver Center |
| 100 Washington Square East |
| New York, NY 10003-6688 |
Email:
Phone: (212) 998-7908 Fax: (212) 995-4015
List of Publications from Pubmed
Lab Homepage
|
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 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.
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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Reexamining microRNA site accessibility in Drosophila: a population genomics study.
PLoS One
Chen K, Maaskola J, Siegal ML, Rajewsky N
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Network hubs buffer environmental variation in Saccharomyces cerevisiae.
PLoS Biol
Levy SF, Siegal ML
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Functional and evolutionary inference in gene networks: does topology matter?
Genetica
Siegal ML, Promislow DE, Bergman A
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Functional conservation and divergence of intersex, a gene required for female differentiation in Drosophila melanogaster.
Dev Genes Evol
Siegal ML, Baker BS
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A genomic analysis of Drosophila somatic sexual differentiation and its regulation.
Development
Arbeitman MN, Fleming AA, Siegal ML, Null BH, Baker BS
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Evolutionary capacitance as a general feature of complex gene networks.
Nature
Bergman A, Siegal ML
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intersex, a gene required for female sexual development in Drosophila, is expressed in both sexes and functions together with doublesex to regulate terminal differentiation.
Development
Garrett-Engele CM, Siegal ML, Manoli DS, Williams BC, Li H, Baker BS
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Waddington's canalization revisited: developmental stability and evolution.
Proc Natl Acad Sci U S A
Siegal ML, Bergman A
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The evolution of dosage-compensation mechanisms.
Bioessays
Marín I, Siegal ML, Baker BS
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Application of Cre/loxP in Drosophila. Site-specific recombination and transgene coplacement.
Methods Mol Biol
Siegal ML, Hartl DL
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Oviposition-site preference in Drosophila following interspecific gene transfer of the Alcohol dehydrogenase locus.
Behav Genet
Siegal ML, Hartl DL
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An experimental test for lineage-specific position effects on alcohol dehydrogenase (Adh) genes in Drosophila.
Proc Natl Acad Sci U S A
Siegal ML, Hartl DL
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Triple-ligation strategy with advantages over directional cloning.
Biotechniques
Siegal ML, Petrov DA, De Aguiar D
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Transgene Coplacement and high efficiency site-specific recombination with the Cre/loxP system in Drosophila.
Genetics
Siegal ML, Hartl DL