Professor Weinreich received his bachelor's degree in computer science from the University of Michigan in 1983. Computer science has a long tradition of interest in the algorithmics of Darwin's paradigm and this provides the formal framework for Weinreich's research. After nine years as a software engineer, he began his graduate studies in evolutionary and population genetics at Harvard University. He received his PhD in 1998 and did postdoctoral work at Brown University (1998-2000), the University of California (2000-2001) and at Harvard University (2001-2006).
Professor Weinreich was appointed an Assistant Professor in the Department of Ecology and Evolutionary Biology at Brown in January 2007, and was promoted to Associate Professor in July 2013. He is also a member of the Center for Computational Molecular Biology at Brown.
|Ogbunugafor, C. Brandon, Wylie, C. Scott, Diakite, Ibrahim, Weinreich, Daniel M., Hartl, Daniel L. Adaptive Landscape by Environment Interactions Dictate Evolutionary Dynamics in Models of Drug Resistance. PLOS Computational Biology. 2016; 12 (1) : e1004710.|
|Baker, C. W., Miller, C. R., Thaweethai, T., Yuan, J., Hollibaugh Baker, M., Joyce, P., Weinreich, D. M. Genetically Determined Variation in Lysis Time Variance in the Bacteriophage X174.. G3&#58; Genes|Genomes|Genetics. 2016;|
|Baker CW, Miller CR, Thaweethai T, Yuan J, Baker MH, Joyce P, Weinreich DM Genetically Determined Variation in Lysis Time Variance in the Bacteriophage φX174.. G3 (Bethesda, Md.). 2016; 6 (4) : 939-55.|
|Ferretti L, Schmiegelt B, Weinreich D, Yamauchi A, Kobayashi Y, Tajima F, Achaz G Measuring epistasis in fitness landscapes: The correlation of fitness effects of mutations.. Journal of Theoretical Biology. 2016; 396 : 132-43.|
|Meini MR, Tomatis PE, Weinreich DM, Vila AJ Quantitative Description of a Protein Fitness Landscape Based on Molecular Features.. Molecular biology and evolution. 2015; 32 (7) : 1774-87.|
|Watson RA, Wagner GP, Pavlicev M, Weinreich DM, Mills R The evolution of phenotypic correlations and "developmental memory".. Evolution. 2014; 68 (4) : 1124-38.|
|Weinreich, Daniel M, Sindi, Suzanne, Watson, Richard A Finding the boundary between evolutionary basins of attraction, and implications for Wright’s fitness landscape analogy. J. Stat. Mech.. 2013; 2013 (01) : P01001.|
|Weinreich DM, Knies JL Fisher's geometric model of adaptation meets the functional synthesis: data on pairwise epistasis for fitness yields insights into the shape and size of phenotype space.. Evolution. 2013; 67 (10) : 2957-72.|
|Weinreich DM, Lan Y, Wylie CS, Heckendorn RB Should evolutionary geneticists worry about higher-order epistasis?. Current opinion in genetics & development. 2013; 23 (6) : 700-7.|
|Liberles DA, Teichmann SA, Bahar I, Bastolla U, Bloom J, Bornberg-Bauer E, Colwell LJ, de Koning AP, Dokholyan NV, Echave J, Elofsson A, Gerloff DL, Goldstein RA, Grahnen JA, Holder MT, Lakner C, Lartillot N, Lovell SC, Naylor G, Perica T, Pollock DD, Pupko T, Regan L, Roger A, Rubinstein N, Shakhnovich E, Sjölander K, Sunyaev S, Teufel AI, Thorne JL, Thornton JW, Weinreich DM, Whelan S The interface of protein structure, protein biophysics, and molecular evolution.. Protein Sci.. 2012; 21 (6) : 769-85.|
|Watson RA, Weinreich DM, Wakeley J Genome structure and the benefit of sex.. Evolution. 2011; 65 (2) : 523-36.|
|Weinreich DM High-throughput identification of genetic interactions in HIV-1.. Nature genetics. 2011; 43 (5) : 398-400.|
|Christin PA, Weinreich DM, Besnard G Causes and evolutionary significance of genetic convergence.. Trends in Genetics. 2010; 26 (9) : 400-5.|
|O'Keefe KJ, Silander OK, McCreery H, Weinreich DM, Wright KM, Chao L, Edwards SV, Remold SK, Turner PE Geographic differences in sexual reassortment in RNA phage.. Evolution. 2010; 64 (10) : 3010-23.|
|Rand DM, Weinreich DM, Lerman D, Folk D, Gilchrist GW Three selections are better than one: clinal variation of thermal QTL from independent selection experiments in Drosophila.. Evolution. 2010; 64 (10) : 2921-34.|
|Lozovsky ER, Chookajorn T, Brown KM, Imwong M, Shaw PJ, Kamchonwongpaisan S, Neafsey DE, Weinreich DM, Hartl DL Stepwise acquisition of pyrimethamine resistance in the malaria parasite.. Proceedings of the National Academy of Sciences. 2009; 106 (29) : 12025-30.|
|Brown KM, Depristo MA, Weinreich DM, Hartl DL Temporal constraints on the incorporation of regulatory mutants in evolutionary pathways.. Molecular biology and evolution. 2009; 26 (11) : 2455-62.|
|Poelwijk FJ, Kiviet DJ, Weinreich DM, Tans SJ Empirical fitness landscapes reveal accessible evolutionary paths.. J. Geophys. Res.. 2007; 445 (7126) : 383-6.|
|DePristo MA, Hartl DL, Weinreich DM Mutational reversions during adaptive protein evolution.. Molecular biology and evolution. 2007; 24 (8) : 1608-10.|
|Weinreich DM, Delaney NF, Depristo MA, Hartl DL Darwinian evolution can follow only very few mutational paths to fitter proteins.. Science. 2006; 312 (5770) : 111-4.|
|Watson RA, Weinreich DM, Wakeley J Effects of intra-gene fitness interactions on the benefit of sexual recombination.. Biochemical Society transactions. 2006; 34 (Pt 4) : 560-1.|
|Polz MF, Hunt DE, Preheim SP, Weinreich DM Patterns and mechanisms of genetic and phenotypic differentiation in marine microbes.. Philosophical Transactions of the Royal Society B: Biological Sciences. 2006; 361 (1475) : 2009-21.|
|DePristo MA, Weinreich DM, Hartl DL Missense meanderings in sequence space: a biophysical view of protein evolution.. Nature reviews. Genetics. 2005; 6 (9) : 678-87.|
|Weinreich DM, Watson RA, Chao L Perspective: Sign epistasis and genetic constraint on evolutionary trajectories.. Evolution. 2005; 59 (6) : 1165-74.|
|Weinreich, Daniel M., Watson, Richard A., Chao, Lin PERSPECTIVE: SIGN EPISTASIS AND GENETIC COSTRAINT ON EVOLUTIONARY TRAJECTORIES. Evolution. 2005; 59 (6) : 1165-1174.|
|Weinreich, Daniel M., Watson, Richard A., Chao, Lin PERSPECTIVE:SIGN EPISTASIS AND GENETIC CONSTRAINT ON EVOLUTIONARY TRAJECTORIES. Evolution. 2005; 59 (6) : 1165.|
|Weinreich, Daniel M., Chao, Lin RAPID EVOLUTIONARY ESCAPE BY LARGE POPULATIONS FROM LOCAL FITNESS PEAKS IS LIKELY IN NATURE. Evolution. 2005; 59 (6) : 1175.|
|Weinreich DM, Chao L Rapid evolutionary escape by large populations from local fitness peaks is likely in nature.. Evolution. 2005; 59 (6) : 1175-82.|
|Weinreich DM The rank ordering of genotypic fitness values predicts genetic constraint on natural selection on landscapes lacking sign epistasis.. Genetics. 2005; 171 (3) : 1397-405.|
|Silander OK, Weinreich DM, Wright KM, O'Keefe KJ, Rang CU, Turner PE, Chao L Widespread genetic exchange among terrestrial bacteriophages.. Proceedings of the National Academy of Sciences. 2005; 102 (52) : 19009-14.|
|Sheldahl LA, Weinreich DM, Rand DM Recombination, dominance and selection on amino acid polymorphism in the Drosophila genome: contrasting patterns on the X and fourth chromosomes.. Genetics. 2003; 165 (3) : 1195-208.|
|Weinreich DM The rates of molecular evolution in rodent and primate mitochondrial DNA.. Journal of molecular evolution. 2001; 52 (1) : 40-50.|
|Weinreich DM, Rand DM Contrasting patterns of nonneutral evolution in proteins encoded in nuclear and mitochondrial genomes.. Genetics. 2000; 156 (1) : 385-99.|
|Rand DM, Weinreich DM, Cezairliyan BO Neutrality tests of conservative-radical amino acid changes in nuclear- and mitochondrially-encoded proteins.. Gene. 2000; 261 (1) : 115-25.|
|Nielsen R, Weinreich DM The age of nonsynonymous and synonymous mutations in animal mtDNA and implications for the mildly deleterious theory.. Genetics. 1999; 153 (1) : 497-506.|
I work on the evolutionary genetics of biological adaptation, in theory and in laboratory populations of microbes.
I am actively seeking new lab members at all levels from High School interns to postdocs. Please click the Teaching tab above and see the BIOL 1950/1960/2980 description for ongoing student projects. Click here to visit the lab web page. Or send me an email describing your background and interests if you would like to join us.
Some time ago I developed novel theory to describe the evolutionary constraints that that mutational interactions impose ( Weinreich 2005 , Weinreich et al. 2005 , Weinreich and Chao 2005 ). Specifically I pointed out that if mutation X unconditionally improves an organism's fitness but Y improves it only in the presence of X, a population's evolutionary trajectory would be constrainted because mutations would only be favored in some temporal order (here, Y must follow X). We designated this form of mutational interaction sign epistasis ( Weinreich et al. 2005 ).
Microbes offer several technical advantages that render them an excellent experimental complement to this theoretical framework. For example, the ease of reverse genetics in E. coli allowed us to construct all 32 combinations of five point mutations in a β-lactamase gene known to jointly increase antibiotic resistance ~100,000-fold. We showed that four of these five mutations exhibit sign epistasis and that as a result, only 18 of the 5! = 120 possible mutational trajectories to this high-resistance quintuple-mutant are selectively accessible ( Weinreich et al. 2006 ).
This finding raises the question of mechanism: what are the functional interactions among these five mutations responsible for this sign epistasis? A simple biophysical model of protein evolution suggests that sign epistasis may occur if mutations pleiotropically perturb multiple phenotypes, each under stabilizing selection ( DePristo, Weinreich and Hartl 2005 ) and we are testing this hypothesis using β-lactamase. We imagine that the drug resistance conferred by each β-lactamase sequence may be decomposed into it's expression level, it's protein product's folding stability, enzymatic properties, etc.
This and several other current projects are detailed under RESEARCH PROJECTS at the top of this page.
Weinreich, Daniel M. (2011) High-throughput identification of genetic interactions in HIV-1. Nature Genetics 43: 398-400. [pdf]
Watson, Richard A., Daniel M. Weinreich and John Wakeley (2010). Genome Structure and the Benefit of Sex. Evolution 65:523 – 536. [pdf]
Lozovsky, Elena, Thanat Chookajorn, Kyle Brown, Daniel M. Weinreich and Daniel Hartl (2009). Stepwise acquisition of pyrimethamine resistance in the malaria parasite. PNAS 106:12015 – 12030. [pdf]
Poelwijk, Frank J., Daniel J. Kivet, Daniel M. Weinreich and Sander J. Tans (2007) Empirical fitness landscapes reveal accessible paths. Nature 445:383-386. doi:10.1038/nature05451
Weinreich, Daniel M., Nigel Delaney, Mark A. DePristo and Daniel L. Hartl (2006). Darwinian evolution can follow only very few mutational paths to fitter proteins. Science 312:111-114.
[pdf] [Supporting Online Material] [Research Highlight in Nature Reviews Genetics]
Weinreich, Daniel M., Richard A. Watson and Lin Chao (2005). Perspectives: Sign epistasis and constraint on evolutionary trajectories. (Cover article) Evolution 59:1165-1174.
DePristo, Mark A, Daniel M. Weinreich and Daniel L. Hartl (2005). Missense meanderings through sequence space: a biophysical perspective on protein evolution. Nature Reviews Genetics 6:678-687.
|Dunn, Casey||Adjunct Professor of Ecology and Evolutionary Biology|
|Edwards, Erika||Adjunct Professor of Ecology and Evolutionary Biology|
|Peti, Wolfgang||Adjunct Professor of Molecular Pharmacology, Physiology and Biotechnology|
|Sello, Jason||Associate Professor of Chemistry|
Society for the Study of Evolution
Member, Faculty of 1000, Evolutionary & Comparative Genetics section in Genomics & Genetics
|BIOL 0370 - Experimental Evolution: Seeing Darwin in Real Time|
|BIOL 0380 - The Ecology and Evolution of Infectious Disease|
|BIOL 1430 - Computational Theory of Molecular Evolution and Population Genetics|
|BIOL 2430 - Topics in Ecology and Evolutionary Biology|
|BIOL 2440 - Topics in Ecology and Evolutionary Biology|