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David Rand, Ph. D., Yale University (1987)

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Title: Professor of Biology
Department: Department of Ecology & Evolutionary Biology

David_Rand@Brown.EDU
+1 401 863 2890, +1 401 863 1063

 
Overview | Research | Grants/Awards | Teaching | Publications

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

7/2013 - present
Chair, Department of Ecology and Evolutionary Biology

7/2003-present
Professor of Biology, Brown University, Providence, RI

7/97-6/03
Associate Professor of Biology, Brown University, Providence, RI

7/1991-6/1997
Assistant Professor of Biology, Brown University, Providence, RI

1/1988-6/1991
Postdoctoral Fellow, Population Genetics, Museum of Comparative Zoology Laboratories, Harvard University

9/1987-12/1987
Postdoctoral Fellow, Institute of Marine Biology, Department of Biology, University of Crete, Greece

9/1981-6/1983
Biology and Mathematics Teacher, St. Albans School Washington, D.C.

9/1980-6/1981
Biology Teaching Fellow, Phillips Academy, Andover, MA


Professional Activities
President, American Genetic Association 2009
Director, IGERT training program in Reverse Ecology 2010-2015
Director, Center for Computational Molecular Biology 2011-present

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, 2004-2009
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

Institutions

Bu

Research Description

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.

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

Funded Research

NIH General Medicine, 2R01GM067862-09
"Nuclear-Mitochondrial Fitness Interactions in Drosophila", $1,351,682, 8/01/12 – 7/31/16, Dr. David Rand, PI., Dr.Zhijin Wu, co-PI

NSF IGERT: Reverse Ecology: Computational Integration of Genomes, Organisms, and Environments, DGE 0966060, $2,900,000 9/2010 - 8/2015
Dr. David Rand, PI.

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

Teaching Experience

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
Reverse Ecology: Computational Integration of Genomes, Organisms and Environments

Courses Taught

  • Current Topics in Ecology and Evolutionary Biology (bi0243)
  • Evolutionary Biology (bi0048)
  • Evolutionary Genetics (bi0141)

Selected Publications

  • Parmakelis A., Kotsakiozi P., Rand D. M. 2013. Animal mitochondria, positive selection and cyto-nuclear coevolution: insights from pulmonates. PLoS One 8(4):e61970. doi: 10.1371/journal.pone.0061970.(2013)
  • Meiklejohn, C. D., Holmbeck, M. A., Siddiq, M. A., Abt, D. A., Rand, D. M., and K. L. Montooth. 2013. An incompatibility between a mitochondrial tRNA and its nuclear tRNA synthetase compromises development and fitness in Drosophila. PLoS Genet. 2013 Jan;9(1):e1003238. doi: 10.1371/journal.pgen.1003238.(2013)
  • Zhu, C. T. and D. M. Rand. 2012. A hydrazine coupled cycling assay validates the decrease in redox ratio under starvation in Drosophila. PLoS ONE 7(10): e47584. doi:10.1371/journal.pone.0047584(2012)
  • Flight, P.A. and D. M. Rand. 2012. Genetic variation in the acorn barnacle from allozymes to population genomics. Integrative and Comparative Biology 52(3):418-29. doi:10.1093/icb/ics099.(2012)
  • Flight P.A., O'Brien, M., Schmidt, P.S., D. M. Rand. 2012. Genetic structure and the North American postglacial expansion of the barnacle, Semibalanus balanoides. J of Heredity 103(2):153-65 doi: 10.1093/jhered/esr083(2012)
  • Pesole, G., J. F. Allen, N. Lane, W. Martin, D. M. Rand, G. Schatz and C. Saccone. 2012. The neglected genome. EMBO Reports 13(6):473-4. doi:10.1038/embor.2012.57. [Epub ahead of print](2012)
  • Flight, P.A., D. Nacci, D. Champlin, A. Whitehead, D. M. Rand. 2011. The effects of mitochondrial genotype on hypoxic survival and gene expression in a hybrid population of the killifish, Fundulus heteroclitus. Molecular Ecology 20:4503–4520. doi: 10.1111/j.1365-294X.2011.05290.x(2011)
  • Gorth, D.J., Rand D.M., Webster TJ . 2011. Silver nanoparticle toxicity in Drosophila: size does matter. Int J Nanomedicine. 20116:343-50(2011)
  • Rand, D. M. 2011. Mitochondrial genome size, population genetics of the germline cytoplasm and the units of selection on Drosophila mtDNA. Genetica 139(5):685-97.(2011)
  • Haney, R.A., B. R. Silliman and D. M. Rand. 2010. Effects of selection and mutation on mitochondrial variation and inferences of historical population expansion in a Caribbean reef fish, Molecular Phylogenetics and Evolution 57: 821–828. doi:10.1016/j.ympev.2010.07.014(2010)
  • Rand, D.M., D. M. Weinreich, Lerman, D., Folk, D. A., G. W. Gilchrist. 2010. Three selections are better than one: Clinal variation of thermal QTL from independent selection experiments in Drosophila. Evolution 64(10):2921-34. doi: 10.1111/j.1558-5646.2010.01039.x.(2010)
  • Mahapatra, C., Bond, J., Rand, D. M., M. D. Rand. 2010. Identification of Methylmercury Tolerance Genes in Drosophila. Toxicological Sciences Sci. 2010 Jul;116(1):225-38.(2010)
  • Flight, P. A., Schoepfer, S., and D. M. Rand. 2010. Physiological stress and the fitness effects of Mpi genotypes in the acorn barnacle Semibalanus balanoides. Marine Ecology Progress Series 404: 139-149.(2010)
  • Montooth, K. L., Meiklejohn, C. D., Abt, D. N., and D. M. Rand. 2010. Mitochondrial-nuclear epistasis affects fitness within species but does not contribute to incompatibilities between species in Drosophila. Evolution 64(12):3364-79. doi: 10.1111/j.1558-5646.2010.01077.x.(2010)
  • Liu, X., Vinson, D., Abt, D., Hurt, R, and D. M. Rand. 2009. Differential toxicity of carbon nanomaterials in Drosophila: Larval dietary uptake is benign but adult exposure causes locomotor impairment and mortality. Environmental Science and Technology, 43(16): 6357–6363.(2009)
  • Montooth, K. L., Abt, D., Hofmann, J, and D. M. Rand. 2009. Comparative genomics of Drosophila mtDNA: variation in evolutionary rates across regulatory elements, oxidative phosphorylation complexes and lineages. Journal of Molecular Evolution 69(1):94-114.(2009)
  • Rand, D. M. 2009. Why genomes in pieces? revisited: Sucking lice do their own thing in mtDNA circle game. Genome Research 19:700-702.(2009)
  • Haney, R. A., Dionne, M. Puritz, J. and Rand, D. M. 2009. The comparative phylogeography of east coast estuarine fishes in formerly glaciated sites: persistence versus recolonization in Cyprinodon variegatus ovinus and Fundulus heteroclitus macrolepidotus. Journal of Heredity 100(3):284-96. PMID: 19091690(2009)
  • Haney, R. A., Turner, B. J. and Rand, D. M. 2009. A cryptic lineage within the pupfish Cyprinodon dearborni suggests multiple colonizations of South America. Journal of Fish Biology 75: 1108-1114.(2009)
  • Schmidt, P.S., Serrão, E. A., Pearson, G. A., Riginos, C. Rawson, P.D., Hilbish, T. J., Brawley, S.H. Trussell, G.C. Carrington, E. Wethey, D.S. Grahame, J.W., Bonhomme, F. and D.M. Rand. 2008. Ecological genetics in the north Atlantic: environmental gradients and adaptation at specific loci. Ecology: 89(11):S91-S107. doi: 10.1890/07-1162.1(2008)
  • Montooth, K, L. and D. M. Rand. 2008. The spectrum of mitochondrial mutations differs across species. PLoS Biology 6(8): e213 doi:10.1371/journal.pbio.0060213(2008)
  • Rand, D. M. 2008. Mitigating mutational meltdown in mammalian mitochondria. PLoS Biology 19;6(2):e35 doi:10.1371/journal.pbio.0060035(2008)
  • Meiklejohn, C. D., Montooth, K, L. and D. M. Rand. 2007. Positive and negative selection on the mitochondrial genome. Trends in Genetics 23(6):259-63.(2007)
  • Haney, R.A., B. R. Silliman and D. M. Rand. 2007. A multi-locus assessment of gene flow and historical demography in the bluehead wrasse (Thalassoma bifasciatum). Heredity 98(5):294-302(2007)
  • Haney, R. A. B. R. Silliman, A. J. Fry, C. Layman and D. M. Rand. 2007. The Pleistocene history of the sheepshead minnow (Cyprinodon variegatus): Non-equilibrium evolutionary dynamics within a diversifying species complex. Molecular Phylogenetics and Evolution 43(3):743-54(2007)
  • Drosophila Comparative Genomics Sequencing and Analysis Consortium (141 authors including Montooth, K. L., Abt, D., D. M. Rand). 2007. Evolution of genes and genomes in the context of the Drosophila phylogeny. Nature, 450(7167):203-18.(2007)
  • Sanford, E., S. B. Holzman, R. A. Haney, D. M. Rand, M. D. Bertness. 2006. Thermal Tolerance of Larvae Regulates the Northern Geographic Range Limit of Fiddler Crabs. Ecology 87(11): 2882-2894.(2006)
  • Rand, D. M., A. J. Fry, and L. A. Sheldahl. 2006. Nuclear-mitochondrial epistasis and Drosophila aging: Introgression of D. simulans mtDNA alters longevity in D. melanogaster nuclear backgrounds. Genetics 172: (1):329-41(2006)
  • Folk, D. A., P. Zwollo, D. M. Rand, G. W. Gilchrist. 2006. Selection for knockdown performance in Drosophila melanogaster impacts thermotolerance and heatshock response differentially in males and females. Journal of Experimental Biology 209(Pt 20):3964-73.(2006)
  • Rand, D.M. 2005. Mitochondrial genetics of aging: Inter-genomic conflict resolution. Science Vol. 2005, Issue 45, Sci. Aging Knowl. Environ., [DOI:10.1126/sageke.2005.45.re5].(2005)
  • Ballard. J. W. O. and D. M. Rand. 2005. The population biology mitochondrial DNA and its phylogenetic implications. Annual Review of Ecology, Evolution and Systematics 36:621-642.(2005)
  • Rand, D. M., R. A. Haney, A. J. Fry. 2004. Cytonuclear coevolution: the genomics of cooperation. Trends in Ecology and Evolution, 19(12):645-653(2004)
  • Fry, A.F., M. R. Palmer, and D. M. Rand. 2004. Variable fitness effects of Wolbachia infection in Drosophila melanogaster. Heredity 93(4):379-389.(2004)
  • Townsend, J. P and D. M. Rand. 2004. Mitochondrial genome size variation in New World and Old World populations of Drosophila melanogaster. Heredity, 93(1):98-103(2004)
  • Comegys, M. M., S.-H. Lin, D. M. Rand, D. E. Britt, D. L. Flanagan, H. M. Callanan, K. Brilliant, D. C. Hixson, 2004 Two variable regions in carcinoembryonic antigen-related cell adhesion molecule1 N-terminal domains located in or next to monoclonal antibody and adhesion epitopes show evidence of recombination in rat but not in human.. Journal of Biological Chemistry 279(33):35063-78(2004)
  • Sheldahl, L. S., D. M. Weinreich, and D. M. Rand. 2003. Recombination, dominance and selection on amino acid polymorphisms in the Drosophila genome. Genetics 165: 1195-1208.(2003)
  • Sackton, T. B., R. Haney, and D. M. Rand. 2003. Cytonuclear coadaptation in Drosophila: Disruptions of cytochrome c oxidase activity in backcross genotypes. Evolution 57:2315-2325(2003)
  • Kingan, S. B., M. Tatar, and D. M. Rand. 2003. Reduced Polymorphism in the Chimpanzee Semen Coagulating Protein, Semenogelin I. J. Mol. Evol. 57:159-169.(2003)
  • Rand, D. M., Spaeth, P. S., Sackton, T, Schmidt, P. S. 2002. Ecological genetics of the Mpi and Gpi polymorphisms in the northern acorn barnacle and the spatial scale of neutral and non-neutral variation. Integrative and Comparative Biology 42:825-836.(2002)
  • Fry, A. F. and D. M. Rand. 2002. Wolbachia interactions that determine Drosophila melanogaster survival. Evolution 56(10): :1976-81(2002)
  • Tatar, M. and D. M. Rand. 2002. Aging: Dietary advice on Q. Science 295:54-55.(2002)
  • Schmidt, P. S., and D. M. Rand. 2001 Adaptive maintenance of genetic polymorphism in an intertidal barnacle: Habitat and life history stage-specific survivorship of Mpi genotypes. Evolution 55(7):1336-44.(2001)
  • Rand, D. M., A. G. Clark, and L. M. Kann 2001. Sexually antagonistic cytonuclear fitness interactions in Drosophila melanogaster. Genetics 2001 159: 173-187.(2001)
  • Rand, D. M. 2001. The units of selection on mitochondrial DNA. Annual Review of Ecology and Systematics 32: 415-448.(2001)
  • Rand, D. M. 2001. Mitochondrial genomics flies high. Trends in Ecology and Evolution 16:2-4(2001)
  • Brown, A. F. L. M. Kann and D. M. Rand, 2001. Gene flow versus local adaptation in the Northern acorn barnacle, Semibalanus balanoides: insights from mtDNA control regions polymorphisms. Evolution 55: 1972–1979.(2001)
  • Rand, D. M., D. M. Weinreich, and B. O Cezairliyan. 2000. Neutrality tests of conservative and radical amino acid changes in nuclear- and mitochondrially-encoded proteins. Gene 291:115-125.(2000)
  • Weinreich, D. M. and D. M. Rand, 2000 Contrasting patterns of non-neutral evolution in proteins encoded in nuclear and mitochondrial genomes. Genetics 2000 156: 385-399.(2000)