Charles F. Aquadro
Vanessa Bauer DuMont
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.
For questions regarding, or access to, published data, please email email@example.com.
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Vanessa "Tessa" Bauer DuMont (Research Support Specialist)
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.
- 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 2009 Gen. Biol. Evol. 2009: 67-74.
- 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.
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My overarching goal is to understand how the function of proteins and their networks change over time, and I develop novel evolutionary tools to this end. I work in a variety of organisms ranging from single cells to primates. Currently I perform experiments in yeast and bacterial cells to retrace the evolution of protein function, while my computational studies are based in yeast species, Drosophila, and mammals.
In January 2012, I will open the Clark Lab in the Department of Computational and Systems Biology at the University of Pittsburgh.
Inferring Functional Relationships through Correlation Evolution
I have developed novel methods to identify protein pairs that exhibit correlation of variation in evolutionary rate. I use this sequence-based signature to create links between functionally related proteins, which can then be experimentally verified. The method can also be used to provide quantitative support for evolutionary hypotheses of coevolution.
Functional Characterization of Adaptive Changes.
Throughout evolution organisms have overcome new challenges through novel adaptations encoded in their DNA. My research dissects historical episodes of adaptive evolution using computational and experimental techniques. The main goals are to understand the functional mechanisms behind protein adaptation and to identify the pressures that are driving them to change. I perform DNA sequence analysis to identify specific genes undergoing positive selection and characterize them with the tools of population genetics and protein structural analysis.
1. Kelleher ES, Clark NL, Markow TA. 2011. Diversity Enhancing Selection Acts on a Female Reproductive Protease Family in Four Sub-Species of Drosophila mojavensis. Genetics. 187(3):865-76. PubMedID 21212232.
2. Clark NL, Aquadro CF. 2010. A novel method to detect proteins evolving at correlated rates: Identifying new functional relationships between coevolving proteins. Molecular Biology and Evolution 27(5):1152-61. Recommended on ‘Faculty of 1000’ website. PubMedID 20044587.
3. Clark NL, Gasper J, Sekino M, Springer SA, Aquadro CF, Swanson WJ. 2009. Coevolution of interacting fertilization proteins. PLoS Genetics 5(7): e1000570. PubMedID 19629160.
4. Dean MD, Clark NL, Findlay GD, Karn RC, Yi X, Swanson WJ, MacCoss MJ, Nachman MJ. 2009. Proteomics and comparative genomic investigations reveal heterogeneity in evolutionary rate of male reproductive proteins in mice (Mus domesticus). Molecular Biology and Evolution. 26(8): 1733. PubMedID 19420050.
5. Karn RC, Clark NL, Nguyen ED, Swanson WJ. 2008. Adaptive evolution in rodent seminal vesicle proteins. Molecular Biology and Evolution. 25(11): 2301. PubMedID 18718917.
6. Clark NL. 2008. Adaptive evolution of primate sperm proteins. In: Encyclopedia of Life Sciences (ELS). John Wiley and Sons, Ltd: Chichester.
7. Clark NL, Findlay GD, Yi X, MacCoss MJ, Swanson WJ. 2007. Duplication and selection on abalone sperm lysin in an allopatric population. Molecular Biology and Evolution. 24(9): 2081. PubMedID 17630281.
8. Clark NL, Aagaard JE, Swanson WJ. 2006. Evolution of reproductive proteins from animals and plants. Reproduction 131(1): 11-22. PubMedID 16388004.
9. Panhuis, TM, Clark, NL & Swanson, WJ. 2006. Rapid evolution of reproductive proteins in abalone and Drosophila. Philosophical Transactions of the Royal Society B 361: 261-268. PubMedID 16612885.
10. Clark NL, Swanson WJ. 2005. Pervasive adaptive evolution in primate seminal proteins. PLoS Genetics 1(3): e35. PubMedID 16170411.
11. Stewart MK, Clark NL, Merrihew G, Galloway EM, Thomas JH. 2005. High genetic diversity in the chemoreceptor superfamily of Caenorhabditis elegans. Genetics 169(4): 1985-1996. PubMedID 15520260.
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Heather Flores (Graduate Student)
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.
- Aruna, S., Flores, H.A., and D. Barbash. 2009. Reduced fertility of Drosophila melanogaster Hybrid male rescue (Hmr) mutant females is partially complemented by Hmr orthologs from sibling species. Genetics: 181(4):1437-50.
- Lazzaro, B.P., Flores, H.A., Lorigan, J.G., and C.P. Yourth. 2008. Genotype-by-environment interactions and adaptation to local temperatureaffect immunity and fecundity in Drosophila melanogaster. PLoS Pathog4(3): e1000025. doi:10.1371/journal.ppat.1000025
- 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: 1291-1295. [* Equal Contribution]
- H. Flores, E. Lobaton, S. Méndez-Diez, S. Tlupova and R. Cortez. 2005. A Study of Bacterial Flagellar Bundling. Bulletin of Mathematical Biology 67:137-168.
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Zhen Wang (Graduate Student)
The Solexa whole-genome sequencing population data recently released (9/14/09) by
Drosophila Population Genomics Project (DPGP) for 37 inbred lines of Drosophila melanogaster from North Carolina is an example of rapid increasing amount of information using next-generation sequencing technologies. With these datasets, it is possible to explore recent evolutionary history in flies with these new short-read resequencing datasets. However, the sequence quality of such datasets is usually low due to the error-prone nature of high-throughput sequencing technologies. Given the large size and low quality/coverage of the data with regard to individual calls for any individual base across all lines, it is necessary to explore which methods can still be used to identify genome-scale selected regions. Haplotype-based methods depend most heavily on common SNPs, thus these approaches might be promising for use on low quality short-read population datasets where a large proportion of sites must be eliminated from the analysis due to missing or poor base calls. I am interested to explore if such haplotype-based methods can be applied on such low-quality data, or if we need to put more efforts on collecting data with better quality in order to identify selection.
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Jae Choi (Graduate Student)
Recently the Aquadro Lab and other labs have found signatures of positive selection across genes that regulate germ line stem cell differentiation and maintenance in Drosophila melanogaster and D. simulans. A crude hypothesis to describe this phenomenon is that germ line parasites such as Wolbachia or Spiroplasm takes advantage of the host germ line and this facilitates adaptive evolution for the host (i.e Drosophila). Specifically Wolbachia is a highly successful endosymbiont/parasite of insects and it is estimated that over 60% of all insect species carry it. Its main effects to the host consist of male-killing, feminization, parthenogenesis, and cytoplasmic incompatibility, which may also be the reason why it is widely dispersed in insects. My main interest is Wolbachia and its coevolution with its host Drosophila. As a first year graduate student, I have a broad interest in the Wolbachia-Drosophila relationship which includes population genetics of the Wolbachia-Drosophila interactions, molecular mechanism of host manipulations induced by Wolbachia, and Wolbachia mediated bidirectional cytoplasmic incompatibility and its possibility as a source of speciation. Currently I am investigating the population genetics of germ line stem cell regulating genes in a range of Drosophila species.
Cutter, A.D. and J.Y. Choi. 2010. Natural selection shapes nucleotide polymorphism across the genome of the nematode Caenorhabditis briggsae. Genome Research 20: 1103-1111.
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Clair Han (Undergraduate)firstname.lastname@example.org
The first part of my project aims to determine whether the unpreferred substitutions observed in D. melanogaster for each of the 100 genes are fixed and caused by selection. I conduct analyses to determine whether the previously observed decouplings between substitutions at synonymous sites and introns are still significant with only fixed differences included in the analyses.
For the second part of the project, I aid the lab in determining the cause of selection for the accumulation of the unpreferred codon at D. melanogaster synonymous sites by making comparisons in expression levels at Notch between D. melanogaster, D. simulans and D. sechellia. The expression level of the Notch gene is crucial to the development of a wide array of organisms, including D. melanogaster and humans. The purpose of such accumulation of unpreferred codons in D. melanogaster might lead to reduction in the efficiency of transcription or translation. It has been hypothesized that the accumulation of unpreferred codons was to reduce translation rate in D. melanogaster, compared to D. simulans and D. sechellia. To test this hypothesis, I monitor the expression of Notch throughout development in D. melanogaster, D. simulans, and D. sechellia and extract mRNA and the protein product of the gene from all three species to compare them against each other in pairs.
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Lisebeth Forbes (Undergraduate)
I am a junior in the College of Arts and Sciences at Cornell University. My academic interests are represented in my double major of biology with a concentration in genetics and development and Classics with a concentration in classical civilization. I have become very interested in research projects that involve both the sciences as well as subjects of the humanities: history, classics, anthropology and archeology. Last semester, I worked as an analyst in the The Malcolm and Carolyn Wiener Laboratory for Aegean and Near Eastern Dendrochronology – Cornell's tree-ring laboratory. This year, I was also a participant in the first Cornell University Genetic Ancestry Project, which functioned within National Geographic's Genographic Project. My interest in this project, which used the principles and techniques of genetics to reveal more about the history of humankind, inspired me to participate in the Aqaudro Lab.
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Alex Han (Undergraduate)
I am a sophomore in the College of Arts and Sciences with a planned major in Biological Sciences with a concentration in genetics and a minor in Computer Sciences. I am largely interested in making genetics more practical for the general public, particularly in the form of medicine. I joined the Aquadro Lab to learn more about the theoretical and procedural aspects of population genetics research. Currently, I assist the other projects in the lab as well as the general maintenance of fly cultures before starting a project of my own.
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Pavitra Muralidhar (Undergraduate Student)
I am a junior in the College of Arts and Sciences in the biology major, with a strong interest in population genetics and evolutionary biology in general. My project has focused on the role of the nanos gene in Drosophila germ line stem cell evolution. Nanos regulates germ line stem cell development in Drosophila species, and along with the pumilo gene, controls the development of the anterior posterior axis in later embreyogenesis. Given the previous signatures of selection found by lab members in genes regulating for germ line stem cell development, my project tries to check the nanos sequence for a similar signature. To accomplish this, I have been sequencing the D. pseudoobscura gene to compare it to the D. melanogaster sequence and thereby test for evidence of positive selection.
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