Lab members:

Charles F. Aquadro

Vanessa Bauer DuMont

Nathan Clark

Heather Flores

Evan Levy

Nadia Singh

Michael C. Turchin

Zhen Wang

Alex Wong

Professor Charles F. Aquadro ("Chip")
cfa1@cornell.edu

My primary interests are in molecular population genetics, molecular evolution, and comparative genomics. Our research efforts are aimed at gaining a conceptual understanding of general principles and processes determining the nature, amount, distribution, and significance of genetic variation within and between natural populations and among related taxa. We draw on the tools of population genetics, molecular evolution, and genomics to study the structure and evolution of the genome, natural populations, and to resolve the evolutionary forces acting on individual genes.  See my faculty page for recent publication list.

Faculty web page including recent publication list: http://www.mbg.cornell.edu/cals/mbg/faculty-staff/faculty/aquadro.cfm
For questions regarding, or access to, published data, please email cfa1@cornell.edu.

Vanessa "Tessa" Bauer DuMont (research support specialist)
vlb2@cornell.edu

Understanding the nature, magnitude, functional targets, and impact of positive and negative selection across a species’ genome is the motivation behind my research.  We have carried out a polymorphism scan of a segment of the genome of Drosophila melanogaster for signals of positive selection (adaptation) that signify functionally important genomic regions.  Our approach compliments those using phylogenetic conservation to predict functional regions.   Much of my research has focused on the Notch locus region of the X chromosome in D. melanogaster where we have detected an acceleration of synonymous substitutions at Notch (favoring classically defined “unpreferred” codons), and an excess of nonsynonymous substitutions in CG18508 consistent with selection for protein diversification.  In addition, we detected a recent selective sweep in non-African populations apparently due to the selective advantage of a new transcriptional binding site predicted upstream of CG18508.  My current work involves computer simulations and functional analyzes to evaluate targets of selection and the evolutionary forces responsible for these signals of selection within the Notch locus region of D. melanogaster.

publications:

• Bauer DuMont VL, EM Hill, JD Jensen and CF Aquadro. Further characterization of patterns of molecular evolution at the Notch locus region of the X chromosome in Drosophila melanogaster. (in preparation)
• Bauer DuMont VL, MH Wright, ND Singh and CF Aquadro. Comparison of GC -increasing and -decreasing substitution rates between synonymous and intron mutations along the Drosophila melanogaster and D. sechellia lineages (in preparation)
• Singh, ND., VL. Bauer DuMont, MJ Hubisz, R. Nielsen, and CF. Aquadro. Patterns of mutation and selection at synonymous sites in Drosophila 2007 Mol Biol Evol 24: 2687-2697
• Jensen JD, VL Bauer DuMont, AB Ashmore, A Gutierrez and CF Aquadro. Patterns of sequence variability and divergecne at the diminutive gene region of Drosophila melangoaster: complex patterns suggest an ancestral selective sweep. 2007 Genetics 177: 1071-1085.
  
• Nielsen, R, VL Bauer DuMont, MJ Hubisz, and CF Aquadro. Maximum likelihood estimation of ancestral codon usage bias parameters in Drosophila. 2007 Mol. Biol. Evol. 24: 228-235
• Bauer DuMont VL, HA Flores, MH Wright, and CF Aquadro. Recurrent positive selection at Bgcn, a key determinant of germline differentiation, does not appear to be driven by simple co-evolution with its partner protein Bam. 2007 Mol Biol Evol 24: 182-191.
  
• Pool JE, Bauer DuMont V, Mueller JL, Aquadro CF. A scan of molecular variation leads to the narrow localization of a selective sweep affecting both Afrotropical and cosmopolitan populations of Drosophila melanogaster. Genetics. 2006 Feb;172(2):1093-105.
• Bauer Dumont V., Aquadro CF. Multiple signatures of positive selection downstream of notch on the X chromosome in Drosophila melanogaster. Genetics. 2005 Oct;171(2):639-53.
• Jensen JD, Kim Y, DuMont VB, Aquadro CF, Bustamante CD. Distinguishing between selective sweeps and demography using DNA polymorphism data. Genetics. 2005 Jul;170(3):1401-10.
  
• Bauer DuMont V., Fay JC, Calabrese PP, Aquadro CF. DNA variability and divergence at the notch locus in Drosophila melanogaster and D. simulans: a case of accelerated synonymous site divergence. Genetics. 2004 May;167(1):171-85.
• Aquadro CF, Bauer DuMont V, Reed FA. Genome-wide variation in the human and fruitfly: a comparison. Curr Opin Genet Dev. 2001 Dec;11(6):627-34. Review.
• Nachman MW, Bauer VL, Crowell SL, Aquadro CF. DNA variability and recombination rates at X-linked loci in humans. Genetics. 1998 Nov;150(3):1133-41.
  
• Bauer VL, Aquadro CF. Rates of DNA sequence evolution are not sex-biased in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1997 Dec;14(12):1252-7. 

Nadia Singh (post-doc)
nds25@cornell.edu

        

The evolution of a genome is governed by the interplay among mutation, natural selection and random genetic drift. My research focuses on characterizing the role of each of these forces in generating heterogeneities in patterns of molecular evolution both within and between genomes, with the long-term goal of understanding the individual and joint contributions of these evolutionary forces. My general approach has been to quantify variation in substitutional patterns and to compare these patterns with the spectrum of genetic changes that have been incorporated into an extant genome. This type of analysis not only helps to illuminate the role of substitution rate heterogeneity in genome evolution, but also is instrumental in identifying instances in which this variation alone is not sufficient to explain patterns of genetic change, potentially implicating the action of natural selection. Currently, I am focusing on assessing the contribution of mutation rate heterogeneity to differences in rates and patterns of evolution within the Drosophila melanogaster genome.

publications:

• Singh, N. D., and D. A. Petrov. DNA loss and Genome Size in Insects: A Synthesis (in preparation).
• Singh, N. D., D. Bensasson, and D. A. Petrov. A Re-evaluation of rates of DNA loss in Podisma grasshoppers (in preparation).
• Singh, N. D., A. M. Larracuente and A. G. Clark. 2008. Contrasting the efficacy of selection on the X and autosomes in Drosophila Molecular Biology and Evolution 25(2):454-467.
• Larracuente, A. M., T. B. Sackton, A. Greenberg, A. Wong, N. D. Singh, D. Sturgill, Y. Zhang, B. Oliver and A. G. Clark. 2007. Protein-coding gene evolution in Drosophila Trends in Genetics 24(3):114-123.
• Singh, N. D., V. L. Bauer DuMont, M. J Hubisz, R. Nielsen, and C. F. Aquadro. Patterns of mutation and selection at synonymous sites in Drosophila 2007 Mol. Biol. Evol. 24: 2687-2697
• Drosophila 12 Genomes Consortium. 2007. Evolution of genes and genomes on the Drosophila phylogeny. Nature 450 (8):203-218.
• Singh, N. D., J. M. Macpherson, J. D. Jensen, and D. A. Petrov. Similar Levels of X-linked and Autosomal Nucleotide Polymorphism in African and non-African strains of Drosophila melanogaster. BMC Evolutionary Biology 7:202.
• Singh, N.D. and D. A. Petrov. 2007. Evolution of gene function on the X chromosome and the autosomes in Jean-Nicolas Volff, ed. Genome Dynamics volume 3: Gene and Protein Evolution. Karger, Wurzburg, Germany.
• Singh, N. D., P. F. Arndt, and D. A. Petrov. 2006. Minor shift in background substitutional patterns in the Drosophila saltans and willistoni lineages is insufficient to explain GC content of coding sequences. BMC Biology 4:37.
• Singh, N. D., J. C. Davis, and D. A. Petrov. 2005. X-linked genes evolve higher codon bias in Drosophila and Caenorhabditis. Genetics 171:145-155.
• Singh, N. D., J. C. Davis, and D. A. Petrov. 2005. Codon bias and Noncoding GC content correlate negatively with recombination rate on the Drosophila X chromosome. Journal of Molecular Evolution 61:315-324.
• Singh, N. D., P. F. Arndt, and D. A. Petrov. 2005. Genomic Heterogeneity of Background Substitutional Patterns in Drosophila melanogaster. Genetics 169:709-722.
• Singh, N. D., and D. A. Petrov. 2004. Rapid sequence turnover at an intergenic locus in Drosophila. Molecular Biology and  Evolution 21:670-680.
• Seielstad, M., N. Yuldasheva, N. Singh, P. Underhill, P. Oefner, P. Shen, and R. S. Wells. 2003. A Novel Y-Chromosome Variant Puts an Upper Limit on the Timing of First Entry into the Americas. American Journal of Human Genetics 73:700-705.
• Srikummool, M., D. Kangwanpong, N. Singh, and M. Seielstad. 2001. Y-Chromosomal Variation in Uxorilocal and Patrilocal Populations in Thailand in L. Jin, M. Seielstad, and C. Xiao, eds. Genetic, Linguistic, and Archeological Perspectives on Human Diversity in Southeast Asia. World Scientific Publishing, River Edge, New Jersey.
• Drici, M. D., S. Ahmad, N. Singh, I. Ducic, R. Glazer, M. Morad, and R. L. Woosley. 1997. Gender difference in I-sK protein in isolated rabbit heart is linked to differences in I-KS in isolated myocytes. Clinical Pharmacology & Therapeutics 61:203.
• Ahmad, S., N. Singh, A. Bellacosa, and R. I. Glazer. 1997. Endogenous regulation of the protooncogene protein serine/threonine kinase, c-AKT by estradiol and insulin growth factor-1 in MCF-7 breast carcinoma cells. Proceedings of the American Association for Cancer Research Annual Meeting 38:232.

Nathan Clark (post-doc)
nlc47@cornell.edu

My research addresses how proteins have adapted during evolution to overcome functional challenges.  Using related coding sequences we can infer which proteins have evolved adaptively, yet our understanding of the forces driving their divergence is not as well developed. Potential forces include functional diversification, co-evolution with an interacting partner, and stabilization of the protein fold.  My work considers evidence for these forces by studying the effects of adaptive substitutions using biochemical, structural, and transgenic approaches. I am currently testing the functional effects of adaptive substitutions in Ovulin, a rapidly evolving reproductive protein in Drosophila.  I also study adaptation among entire protein families using related genome sequences and protein structural models. Finally, I have developed a maximum likelihood method to detect correlated rates of evolution between coevolving protein pairs. Overall, a deeper understanding of the causes behind adaptive substitutions should reveal which protein properties are acted on by natural selection and provide needed clues for many proteins of unknown function.
My publications include:

• Clark, N. L., S. A. Springer, C. F. Aquadro, and W. J. Swanson. 2008. Coevolution of Interacting Fertilization Proteins. (submitted).
• Karn, R. C., N. L. Clark, E. D. Nguyen, W. J. Swanson. 2008. Adaptive Evolution in Rodent Seminal Vesicle Secretion Proteins. (submitted).
• Clark, Nathaniel L. 2008. Adaptive Evolution of Primate Sperm Proteins. In: ENCYCLOPEDIA OF LIFE SCIENCES. John Wiley & Sons, Ltd: Chichester http://www.els.net/ [DOI: 10.1002/9780470015902.a0020775]
• Clark, N. L., G. D. Findlay, X. Yi, M. J. Maccoss, and W. J. Swanson. 2007. Duplication and selection on abalone sperm lysin in an allopatric population. Molecular biology and evolution 24:2081-2090.
• Clark, N. L., J. E. Aagaard, and W. J. Swanson. 2006. Evolution of reproductive proteins from animals and plants. Reproduction 131:11-22.
• Panhuis, T. M., N. L. Clark, and W. J. Swanson. 2006. Rapid evolution of reproductive proteins in abalone and Drosophila. Philosophical transactions of the Royal Society of London.Series B, Biological sciences 361:261-268.
• Clark, N. L., and W. J. Swanson. 2005. Pervasive adaptive evolution in primate seminal proteins. PLoS genetics 1:e35.
• Stewart, M. K., N. L. Clark, G. Merrihew, E. M. Galloway, and J. H. Thomas. 2005. High genetic diversity in the chemoreceptor superfamily of Caenorhabditis elegans. Genetics 169:1985-96.

Heather Flores
haf22@cornell.edu

I am interested in using population genetic inference and functional analyses to understand the evolution of genes involved in germline stem cell maintenance and differentiation in Drosophila. Previous work by our lab and others has identified numerous proteins involved in these processes to be undergoing rapid, adaptive evolution. I am currently working to characterize this pathway in terms of which proteins are and are not rapidly evolving and what role coevolution has played.  Once such proteins are identified, I plan to test the functional consequences of this rapid evolution. By combining these methods, I ultimately want to identify the biological force causing the evolution of this pathway.

publications:

• Lazzaro, B.P., Flores, H.A., Lorigan, J.G., and C. P. Yourth.  Genotype by Environment Interactions and Adaptation to Local Temperature Affect Immunity and Fecundity in Drosophila melanogaster (submitted).
• Bauer DuMont, V.L., Flores, H.A., Wright, M.H., and C.F. Aquadro. 2007. Recurrent positive selection at Bgcn, a key determinant of germline differentiation, does not appear to be driven by simple co-evolution with its partner protein Bam.  Molecular Biology and Evolution 24: 182-91.
• Brideau, N.J., Flores, H.A., Wang, J., Maheshwari, S., Wang, X., and D.A. Barbash. 2006.  Two Dobzhansky-Muller genes interact to cause hybrid lethality in Drosophila.  Science, 314: 1292 - 1295.
• Flores, H., Lobaton, E., Mendez-Diez, S., Tlupova, S., and R. Cortez, 2005. A Study of Bacterial Flagellar Bundling. Bulletin of Mathematical Biology, 67:137-168.

Alex Wong (graduate student)
aw246@cornell.edu

I am interested in the molecular evolution of reproductive proteins, a class of molecules that shows an abundance of positive selection  in many organisms.  It has been suggested that interactions between male and female derived molecules may drive the rapid, adaptive evolution of some reproductive proteins, such as the Drosophila seminal fluid protein ovulin. In order to gain further insight into this hypothesis, I am studying the molecular evolution of candidate reproductive genes from both the male and female reproductive tracts of D. melanogaster. In addition, I am characterizing the self-interaction domain of ovulin (an egg-laying hormone), particularly with regard to the role of conserved tertiary structure in determining ovulin's evolvability.

publications:

• Larracuente AM, Sackton TB, Greenberg AJ, Wong A, Singh ND, Sturgill D, Zhang Y, Oliver B, Clark AG. In press. Evolution of protein-coding genes in Drosophila. Trends in Genetics.
• Wong A, Turchin MC, Wolfner MF, Aquadro CF. Epub. 2007. Evidence for positive selection on Drosophila melanogaster seminal fluid protease homologs. Molecular Biology and Evolution 25:497-506.
  
• Drosophila 12 Genomes Consortium. 2007.  Evolution of Genes and Genomes on the Drosophila Phylogeny.  Nature 450: 203-18.
• Haerty S, Jagadeeshan S, Kulathinal R, Wong A, Ravi Ram K, Sirot LK, Levesque L, Artieri C, Wolfner MF, Civetta A, Singh R. 2007. Evolution in the fast lane: rapidly evolving sex-and reproduction-related genes in species of the genus Drosophila. Genetics 177: 1321-35.
• Williams BC, Leung G, Maiato H, Wong A, Li Z, Williams E, Kirkpatrick C, Aquadro C, Rieder CL, Goldberg ML. 2007. Mitch: A Rapidly Evolving Component of the Ndc80 Kinetochore Complex Required for Proper Chromosome Segregation in Drosophila. Journal of Cell Science 120: 3522-33.
• Jensen JD, Wong A, Aquadro CF. On statistical and functional approaches for identifying targets of positive selection. Trends in Genetics 23: 568-77.
• Buston PM, Bogdanowicz SM, Wong A, Harrison RG. 2007. Are clownfish groups composed of close relatives?  An analysis of microsatellite DNA variation in Amphiprion percula. Molecular Ecology 16(17): 3671-8.
• Wong A, Jensen JD, Pool JE, Aquadro CF. 2007. Phylogenetic incongruence in the melanogaster species group. Mol Phy Evol 43(3): 1138-50. Epub. 2006 Sep 9.
• Wong A, Albright SN, Wolfner MF. 2006. Evidence for structural constraint on ovulin, a rapidly evolving Drosophila melanogaster seminal protein. Proc Natl Acad Sci USA 103:18644-9.
• Wong A, Wolfner MF. 2006. Sexual behavior: a seminal peptide stimulates appetites. Current Biology 16(7):R256-7.
• Pool JE, Wong A, Aquadro CF. 2006. Finding of male-killing Spiroplasma infecting Drosophila melanogaster in Africa implies transatlantic migration of this endosymbiont. Heredity 97(1): 27-32.
• Swanson WJ, Wong A, Wolfner MF, Aquadro CF. 2004. Evolutionary EST analysis of Drosophila female reproductive tracts identifies several genes subjected to positive selection. Genetics 168(3): 1457-65.
• Wong A, Smith ML, Forbes MR.  2003.  Differentiation between subpopulations of a polychromatic damselfly with respect to morph frequencies, but not neutral genetic markers.  Molecular Ecology 12(12):3505-13.
• Yan H, Aziz E, Shillabeer G, Wong A, Shanghavi D, Kermouni A, Abdel-Hafez M, Lau DC. 2002. Nitric oxide promotes differentiation of rat white preadipocytes in culture. Journal of Lipid Research 43(12): 2123-9.
• Wong A, Forbes MR, Smith ML.  2001.  Characterization of AFLP markers in damselflies: prevalence of codominant markers and implications for population genetic applications.  Genome 44: 677-84.

Zhen Wang (graduate student)
zw47@cornell.edu

  new student

Michael C. Turchin  (undergraduate student)
mct42@cornell.edu

       

I am currently working with graduate student Alex Wong to help identify genes undergoing positive selection. It has been previously hypothesized that sexual conflict can lead to adaptive evolution. Within Drosophila, accessory gland proteins in males have a wide range of effects upon the female, including decreased sexual receptivity, increased egg laying and decreased life span. Positive selection and adaptive evolution may be occurring in this sexual interaction, as previous research on accessory gland genes suggest. To further elucidate the forms of selection acting on this system, I am specifically looking at genes involved with the accessory gland protein processing.

publications:

• Wong, A., M.C. Turchin, M.F. Wolfner and C.F. Aquadro. 2008.  Evidence for positive selection on Drosophila melanogaster seminal fluid protease homologs. Molecular Biology and Evolution 25(3):497-506

Evan Levy (undergraduate student)
ejl33@cornell.edu