David Rand
Professor:
Ecology & Evolutionary Biology
Phone: +1 401 863 2890
Phone 2: +1 401 863 1063
David_Rand@Brown.EDU
Professor David Rand is interested in how natural selection acts on genes and genomes. One major focus of his research is how the mitochondrial genome and its interactions with the nuclear genome influence animal performance, evolutionary fitness, and aging. A second major interest is how thermal selection influences the genetic composition of populations. The goals of this work are to identify the genetic interactions that allow organisms to adapt to environmental heterogeneity.
Biography
Education
9/83-8/87
Yale University, Department of Biology, Ph. D. September 1987
9/75-6/80
Harvard College, B. A., Biology, cum laude, June 1980
PROFESSIONAL EXPERIENCE
7/03-present
Professor of Biology, Brown University, Providence, RI
7/97-6/03
Associate Professor of Biology, Brown University, Providence, RI
7/91-6/97
Assistant Professor of Biology, Brown University, Providence, RI
1/88-6/91
Postdoctoral Fellow, Population Genetics, Museum of Comparative Zoology Laboratories, Harvard University
9/87-12/87
Postdoctoral Fellow, Institute of Marine Biology, Department of Biology, University of Crete, Greece
9/81-6/93
Biology and Mathematics Teacher, St. Albans School Washington, D.C.
9/80-6/81
Biology Teaching Fellow, Phillips Academy, Andover, MA
Professional Activities
Memberships
Genetics Society of America, Society for the Study of Evolution, Society for Molecular Biology and Evolution, Society of Systematic Biologists
Associate Editor
Molecular Biology and Evolution, 1997-2000; 2000-2003
Genetics, 2004-present
BioScience, 2005-present
Reviewer
American Naturalist, Evolution, Genetics, Journal of Molecular Evolution, Molecular Biology and Evolution, Nature, Science, NSF Population Biology, NSF Systematics, NSF Eukaryotic Genetics, NSERC
Panel Member
NSF Population Biology 10/95, 10/97, 4/98, 4/05
NIH Program Project Advisory Panel, 7/99, SEP 3/05
NIH Genetic Variation and Evolution Study Section 10/2008-10/2012
Interests
Evolutionary Genetics of Mitochondrial Genomes
The mitochondrion is the powerhouse of the eukaryotic cell, consuming 90% of the oxygen we breathe and generating 90% of the energy we need to stay alive. This organelle evolved from a symbiotic association between two divergent microbes that began about 2 billion years ago. Modern day mitochondria house small, circular genomes that have been shaped by reductive evolution through gene loss and transfer to the nuclear genome. As a result, mitochondrial function depends critically on cross talk between hundreds of nuclear-encoded genes and the three-dozen genes encoded in the mitochondrial genome. Thus "mitonuclear" interactions provide rich material for the study of co-evolution and the dissection of metabolic diseases. We are approaching these problems from several angles: 1) the molecular bases of evolutionary change in mitochondrial genes and genomes, 2) the fitness consequences of variation in nuclear-mitochondrial interactions, and 3) the mitochondrial genetics of aging. For this work we use Drosophila as a model system.
Molecular Evolution of mtDNA. DNA sequencing surveys of synonymous and amino acid replacement changes in protein coding genes reveal that mtDNA evolution is not consistent with neutral models of DNA evolution, showing an excess of low frequency amino acid variation consistent with the action of purifying selection. Recent progress with the Drosophila Species Genome Projects has allowed us to mine mtDNA and nuclear gene sequences from the 12 new genome projects, spanning 50 million years of divergence. Comparisons of these protein sequences reveal significant functional variation among the five enzyme complexes of the electron transport chain that generates cellular energy. Future work will involve computational modeling of amino acid substitutions in defined protein structures and functional assays of the genetic interactions governing enzyme activity of these five enzyme complexes.
Fitness Consequences of Mitonuclear Interactions in Drosophila. We examine the functional genomics of joint mitonuclear interactions by placing alternative mtDNAs onto defined nuclear genetic backgrounds. Typical experiments involve population cage competition experiments, or specific chromosome inheritance assays where we can measure the evolutionary fitness of genotypes carrying different combinations of nuclear and mitochondrial genomes. We use genetic crosses to construct strains of flies carrying their own mtDNA on a native set of chromosomes (the "home team") and compare these to a strain of flies carrying a foreign mtDNA on the same set of nuclear chromosomes (the "away team"). The rich genetics of Drosophila offers many ways to manipulate mitonuclear genotypes for functional analysis of whole animals or enzyme activities. Recent studies have identified a specific gene on chromosome 2 that shows strong epistatic interactions with particular mtDNA genotypes. These experiments seek to dissect the genetic interactions underlying metabolic diseases.
Mitochondrial Genetics of Aging. A leading hypothesis for the cause of aging is the production of reactive oxygen species in the mitochondria. We are testing this hypothesis using genetic manipulations of nuclear-mitochondrial interactions. We have shown that alternative mtDNAs alter the patterns of aging in a nuclear-background dependent manner. We have further shown that mitochondrial genotype alters the longevity-extending effects of dietary restriction, and that hypomorphic mutations of insulin signaling (chico) can rescue this mitochondrial defect.
Evolutionary Genetics of Thermal Stress
We have conducted thermal selection experiments that have altered the genetically based thermal tolerance of Drosophila. Through continuous culture at different temperatures, or selective breeding of temperature resistant vs. temperature sensitive flies, we have constructed genetically differentiated strains of Drosophila. Using genomic scans of molecular markers, we have identified a gene region that is responsible for part of this phenotype. We are in the process of fine-scale mapping and mutant analysis to identify the gene involved. Our current candidate gene region also shows latitudinal variation in allele frequency, suggesting that this gene plays a general role in adaptation to different climates.
Ecological Genetics of Barnacles. We have shown that barnacles from different tidal heights in the intertidal zone are genetically differentiated for key enzymes of glycolysis. Alternative homozygotes of the Mpi and Gpi allozyme loci show significant tidal-height zonation, with Mpi exhibiting strong zonation in Maine and Gpi showing zonation in Rhode Island. Survivorship experiments with the substrates of these enzymes (mannose and glucose, or different plankton) indicate that genotype zonation is mediated by the combined effect of thermal stress and the availability of these sugars in the diet. Sequence analyses of the Mpi locus have identified the specific amino acid change that causes the enzyme polymorphism and sequence polymorphism surveys indicate that balancing selection has operated at this locus.
Degrees
Ph. D., Yale University (1987)
Awards
President, American Genetic Association, 2009
Elected Chair, Gordon Research Conference, Molecular Evolution
Marine Biological Laboratory, Summer Research Fellowship, 2005
Editorial Board, Molecular Biology and Evolution, 1997-2000; 2000-2003
Editorial Board, Genetics, 2004–present
Editorial Board, BioScience, 2005-present
NSF 5-year research award, 1991-1996
NIH National Research Service Award Postdoctoral Fellowship
Affiliations
Genetics Society of America
Society for the Study of Evolution
Society for Molecular Biology and Evolution
Teaching
Evolutionary Biology
A broad introduction to the patterns and processes of evolution at diverse levels of biological organization. Topics covered include natural selection, adaptation, speciation, systematics, macroevolution, mass extinction events, and human evolution. Weekly discussion sections involve debates on original research papers. Occasional problem sets involve computer exercises with population genetics and phylogeny reconstruction.
Evolutionary Genetics
This course focuses on selected topics in molecular population genetics, molecular evolution, and comparative genomics. Classic and current primary literature at the interface of evolution and genetics is discussed in a seminar format. The laboratory involves wet-lab exercises (allozymes, PCR-RFLP, sequencing), plus computer labs using DNA analysis packages. Students will prepare a final grant proposal on specific research interests.
Graduate Seminars
Molecular Evolution
Systematics
Quantitative Genetics
Environmental Genomics
The Neutral Theory in Ecology and Evolution
Funded Research
NIH National Institute on Aging, 1R01AG027849
"Mitochondrial Genetics of Aging in Drosophila", $1,614,000, 10/01/09 – 9/30/2014, Dr. David Rand, PI.
NIH General Medicine, 2R01GM067862
"Nuclear-Mitochondrial Fitness Interactions in Drosophila", $1,267,400, 8/01/08 – 7/31/12, Dr. David Rand, PI.
"Evolutionary Response to Nanomaterial Exposure in the Environment: Functional Genomics of C60-Resistance in Drosophila", Brown University Seed Fund Program, $55,000, P.I. D.M Rand, with K. Wharton (MCB) and R. Hurt (Engineering).
NSF EPS 05-54548
"Rhode Island EPSCoR: Catalyzing a Research, Education and Innovation Network"
Dr. Jeff Seeman, PI;
7/2006–6/2009, $6,750,000
D. Rand, Brown University Graduate Director ($375,000 in graduate fellowships)
NIH General Medicine, R01 GM067862
"Nuclear-mitochondrial fitness interactions in Drosophila"
Dr. David Rand, PI; Dr. Bill Ballard, Co-Investigator
8/01/2004–7/31/2008, $1,095,301
NSF Population Biology, DEB 0343464
"Genetic architecture of thermal selection in Drosophila"
Collaborative Research Award with George Gilchirst at William and Mary
3/01/2004–2/28/2007, $536,000 ($281,000 to Brown University)
NSF Population Biology, DEB 0108500
"Nucleotide polymorphism in heterogeneous environments: MPI in Semibalanus"
Dr. David Rand, PI
9/1/2001–8/31/2004, $262,000
NSF Population Biology, DEB 9981497
"Recombination, dominance, and selection on amino acid mutations"
Dr. David Rand, PI; Dan Weinreich, Co-PI
3/1/2000-2/28/2002, $172,367
NIH-1RO1AG16632-01
"Longevity and candidate gene polymorphisms in Drosophila"
Dr. Marc Tatar, PI; Dr. David Rand, Co-PI
7/1/1999-6/30/2004, $1,505,510
NSF International Programs, INT-9815899
"US-France Cooperative Research: Molecular population genetics of New World and Old World Drosophila"
Dr. David Rand, PI; Dr. Michel Veuille, Collaborator, Univ. of Paris
3/1/1999-2/29/2000, $6,740; 3/2001-4/2003, $15,460
NSF Population Biology, DEB 9707676
"Evolutionary dynamics of mitochondrial DNA"
Dr. David Rand, PI
9/1997-8/2000, $210,000
NSF Population Biology, BSR-9527709
"Molecular Ecological Genetics of the Acorn Barnacle"
Dr. David Rand, PI; Dr. Mark Bertness Co-PI
3/1996-2/1999, $215,000
NSF Biological Instrumentation and Resources, BIR-9513001
"An Automated DNA Sequencer for Brown University"
Dr. David Rand, PI; Dr. Edward Hawrot Co-PI
12/1995-11/1996, $70,000
NSF Population Biology, BSR-9120293
"Experimental Population Genetics of Drosophila Mitochondrial DNA"
Dr. David Rand, PI
1/15/1992-6/14/1997, $602,000
Biomedical Research Support Grant, Brown University
"The Evolution and Maintenance of Asexuality in the Planarian Dugesia tigrina"
(with A. Fausto-Sterling, Johanna Schmitt, Lisa Brooks)
7/1991-6/1992, $7,000
NIH NRSA Postdoctoral Fellowship
"Population Genetics of Mitochondrial DNA Size Variation"
1988-1990, $68,000
Grants-in-aid-of-Research, Sigma Xi,
2/1986, $500
NIH Predoctoral Training Grant in Genetics, Yale University
1984-1987
Dudley Leyland Wadsworth Fellowship, Yale University
1983-1984
