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Thomas G. Doak

Postdoctoral Research Associate

tdoak(at)indiana.edu

(812) 856-0115

Research Specialist, University of Oregon, Eugene, with Rick Dahlquist: Biochemistry of bacterial chemotaxis in E. coli. 1982-1984
Graduate Student, University of Utah, Salt Lake City, with John Roth: Genetics of vitamin B12 biosynthesis in Salmonella. 1985-1991
Graduate Student, University of Utah, Salt Lake City, with Glenn Herrick:Transposon excision in ciliated protozoa. 1992-2001
Ph.D. in Genetics: Transposons in Ciliated Protozoa. University of Utah, Salt Lake City. 2001
Postdoctoral Work, University of Utah, Salt Lake City, with Glenn Herrick: Analyses of a pilot Oxytricha genome project. 2001-2012
Lead writer, NHGRI & JGI proposals to sequence the Oxytricha trifallax micronuclear & macronuclear genome. Both projects are approved by NHGRI. 2002
Lead writer, NHGRI & JGI proposals to sequence the genomes of multiple species of the dinoflagellate Symbiodinium 2003
Research Staff, Princeton University, Evolution and Ecology, with Laura Landweber: Evolution of protist genomes Fall 2003-Fall 2006
Director, Molecular Genetics Training Lab, Princeton, Evolution and Ecology Training ecologists in molecular methods specific to their research Fall 2003-Fall 2006
Research Associate, Lab of Michael Lynch, Dept. of Biology, Indiana University. The genomics of Paramecium species.
Domain Science Liaison, National Center for Genome Analysis Support (NCGAS.org), Indiana University. The NSF-funded center aids the biological research community in analyzing, understanding, and making use of the vast amount of genomic information now available. NCGAS focuses particularly on genome-level assembly, phylogenetics, metagenomics and community genomics. 2012-present.

Scientific interests

My scientific interests center on protozoa, especially ciliated protozoa, and include several different biological problems. I think of these interests in three categories: 1) The biochemical activities responsible for the differentiation of a micronucleus to a terminally differentiated macronucleus. These activities include site-specific recombination, site-specific chromosome cleavage, and telomere addition. 2) The diversity and evolution of transposons in ciliates. Both the structure and propagation of transposons in ciliate genomes is unique among the eukaryotes. 3) The structure and contents of ciliate genomes. Ciliates are gene-rich, complex eukaryotes, and their genomes have developed novel structures, which are suggested to allow novel pathways of genome evolution. I’m involved in two ongoing projects:
 • Endosymbiotic bacteria are intrinsically interesting, and there is a long history of studying them in Paramecium and other ciliates, where they can have dramatic effects on their host’s biology and ecology. This project proposes to sequence the genomes of several Caedibacter proteobacterial inhabitants of Paramecium, which are well-known for their ability to rapidly kill Caedibacter-free Paramecia without direct contact among host cells. Although the precise killing mechanism is unknown, it is associated with a large bacterial inclusion (the R body, encoded by reb genes), as well as with plasmid and/or phage activity. We have done extensive informatics, to locate reb proteins in published genomes (in collaboration with Simonetta Gribaldo @ the Pasteur) and are collaborating with a consortium of European labs to sequence more Caedibacter genomes.
 • The population biology and speciation of Paramecium species has been actively studied for 80 years, and has made fundamental contributions to the concept of “species.” We are using the genomes of Paramecium species to study the consequences of whole-genome duplications (WGD; polyploidization). WGD can have significant and lasting effects on a species and its descendent lineages, and has played a role in the evolution of many lineages, including vertebrates.  New gene duplicates provide substrates for the evolution of novel genes and gene functions, and differential loss of duplicate genes in subpopulations may lead to reproductive isolation and rapid speciation.  The genomes of Paramecium aurelia species show evidence of at least three past WGDs (Aury et al. 2006), and the most recent genome duplication shortly predates the rise of the P. aurelia species complex of 15 morphologically identical species. We are sequencing the genomes of all P. aurelia species and several out-group species, as well as generating RNA seq data, in order to decipher the outcomes of WGD in each species.
 We hope that this will solve not only long-standing mysteries in Paramecium biology, but be applicable to a general understanding of gene duplication and loss. Clearly, I would like to extend the studies of Paramecium populations into the Oxytricha species. This would pair nicely with the Oxytricha genome project that collaborators and I initiated—just published last year.
While my current interests are perhaps mostly molecular evolution, my background has been in mixed biology departments, and I can generally talk that talk, and my brother Dan and sister Pat are both ecologists.

Publications

Kehry, M.R., T.G. Doak & F.W. Dahlquist. 1984. Stimulus-induced changes in methylesterase activity during chemotaxis in Escherichia coli. J. Biol. Chem. 259:11828- 11836.

Kehry, M.R., T.G. Doak & F.W. Dahlquist. 1985. Aberrant regulation of methylesterase activity in cheD chemotaxis. J. Bact. 163:105-112.

Kehry, M.R., T.G. Doak & F.W. Dahlquist. 1985. Sensory adaptation in bacterial chemotaxis: regulation of demethylation. J. Bact. 163:983-990.

Roth, J.R., C. Grabau & T.G. Doak. 1990. Genetic approaches to the synthesis and physiological significance of B12 in Salmonella typhimurium. Chemical Aspects of Enzyme Biotechnology. Ed. T.O. Baldwin et al., Plenum Press, New York.

Williams, K., T.G. Doak & G. Herrick. 1993. Precise excision of Oxytricha trifallax Telomere-Bearing Elements and formation of circles closed by a copy of the flanking target duplication. EMBO J. 12:4593-4601.

Doak, T.G., F.P. Doerder, C. Jahn & G. Herrick. 1994. A family of transposase genes in transposons found in prokaryotes, multicellular eukaryotes and ciliated protozoans. Proc. Natl. Acad. Sci. USA 91:942-946.

Seegmiller, A., K.R. Williams, R.L. Hammersmith, T.G. Doak, T. Messick, D.J. Witherspoon, L.L. Storjohann & G. Herrick. 1996. Internal eliminated sequences of Oxytricha: allelic fixation, divergence, conservation and conversions. Mol. Biol. Evol. 13:1351-1362.

Witherspoon, D.J., T.G. Doak, K. Williams, J. Seger & G. Herrick. 1997. Selection on the protein-coding genes of the TBE1 family of transposable elements in the ciliates Oxytricha fallax and O. trifallax. Mol Biol Evol. 14:696-706.

Doak, T.G., D.J. Witherspoon, F. Doerder, K. Williams & G. Herrick. 1997. Conserved features of ciliate TBE1 transposons. Genetica 101:75-86.

Doak, T.G. 2001. Ph.D. Dissertation. Transposons in ciliated protozoa. University of Utah, Salt Lake City.

Williams KR, T.G. Doak & G. Herrick 2002. Telomere formation on macronuclear chromosomes of Oxytricha trifallax and O. fallax: alternatively processed regions have multiple telomere addition sites. BMC Genetics 3:16.

Doak T.G., D.J. Witherspoon, C. Jahn & G. Herrick 2003. Selection on the genes of Euplotes crassus Tec1 and Tec2 transposons:evolutionary appearance of a programmed frameshift in a Tec2 gene encoding a tyrosine-family, site-specific recombinase. Eukaryotic Cell, 2:95-102.

Doak T.G., A.R.O. Cavalcanti, N.A. Stover, D.M. Dunn, R. Weiss, G. Herrick & L.F. Landweber. 2003. Sequencing the Oxytricha trifallax macronuclear genome: a pilot project. Trends Genet. 19:603-607.

Cavalcanti ARO, Stover NA, Orecchia L, Doak T.G, Landweber L.F. 2004. Coding properties of Oxytricha trifallax (Sterkiella histriomuscorum) macronuclear chromosomes: analysis of a pilot genome project. Chromosoma. 113:69-76.

Cavalcanti ARO, DM Dunn, R Weiss, G Herrick, LF. Landweber and TG. Doak. 2004. Sequence features of Oxytricha trifallax (Class Spirotrichea) macronuclear telomeric and subtelomeric sequences. Protist 155:311–322.

W-J Chang, TG Doak 2006. Mechanisms and evolution of genome reorganization in ciliated protozoa. Endocytobiosis Cell Res. 17:119-124.

Nowacki M, Vijayan V, Zhou Y, Schotanus K, Doak TG, Landweber LF. 2008. RNA-mediated epigenetic programming of a genome-rearrangement pathway. Nature. 451:153-8.

Moenbeck M, Zhou Y, Cavalcanti ARO, Jonsson F, Chang WJ, Juranek S, Doak TG, Rozenberg G, Lipps HL, and Landweber LF. Submitted. The pathway for detangling a scrambled gene.

Richard A. Holland, Joseph L. Kirschvink, Thomas G. Doak, and Martin Wikelski. Bats use magnetite to detect the earth’s magnetic field. PloS ONE. 3:e1676.

Nowacki M, Higgins BP, Maquilan GM, Swart EC, Doak TG, and Landweber LF. 2009. A functional role for transposases in a large eukaryotic genome. Science 324:935-8

Ye Y, Doak TG. 2009. A Parsimony Approach to Biological Pathway Reconstruction/Inference for Genomes and Metagenomes. PLoS Comput Biol 5(8): e1000465.

Neethu Shah, Haixu Tang, Thomas G. Doak and Yuzhen Ye. 2011. Comparing bacterial communities inferred from 16S rRNA gene sequencing and shotgun metagenomics. Pac Symp Biocomput. 2011:165-176.

Mina Rho, Yu-Wei Wu, Haixu Tang, Thomas G. Doak, Yuzhen Ye. 2011. Diverse CRISPRs evolving in human microbiomes. PLOS Genetics. PLoS Genet 8(6): e1002441. doi:10.1371/journal.pgen.1002441.

Stephen D. Zoller, Robert L. Hammersmith, Brian P. Higgins, Estienne Swart, Thomas G. Doak, Glenn Herrick, and Laura F. Landweber. 2011. Characterization and taxonomic validity of the ciliate Oxytricha trifallax (Class Spirotrichea) based on multiple conserved gene sequences: limitations and problems in identifying ciliate genera by only morphology. Protist. 163:643–657.

Estienne C. Swart, Mariusz Nowacki, Justine Shum, Heather Stiles, Brian P. Higgins, Thomas G. Doak, Klaas Schotanus, Vincent J. Magrini, Patrick Minx, Elaine R. Mardis and Laura F. Landweber1. 2011. The Oxytricha trifallax mitochondrial genome. Genome Biology and Evolution, 4: 136-154.

Quan Zhang, Thomas G. Doak, YuZhan Ye. 2012. Artificial functional differences between microbial communities caused by length differences of sequencing reads. Pac Symp Biocomput. 2012:259-70.

Yu-Wei Wu, Mina Rho, Thomas G. Doak, Yuzhen Ye. 2012. Oral spirochetes implicated in dental diseases are widespread in normal human subjects and carry extremely diverse integron gene cassettes. Appl Environ Microbiol. 78:5288.

Yu-Wei Wu, Mina Rho, Thomas G. Doak, and Yuzhen Ye. 2012. Stitching Gene Fragments with a Network Matching Algorithm Improves Gene Assembly for Metagenomics. ECCB.

Ke Xu, Thomas G. Doak, Hans J. Lipps, Jingmei Wang, Estienne C. Swart, Wei-Jen Chang. 2012. Copy number variations of 11 macronuclear chromosomes and their gene expression in Oxytricha trifallax. Gene. 505:75-80.

Sung W, Tucker AE, Doak TG, Choi E, Thomas WK, Lynch M. 2012. Extraordinary genome stability in the ciliate Paramecium tetraurelia. Proc Natl Acad Sci U S A. 109:19339-19344

Swart EC, Bracht JR, Magrini V, Minx P, Chen X, et al. (2013) The Oxytricha trifallax Macronuclear Genome: A Complex Eukaryotic Genome with 16,000 Tiny Chromosomes. PLoS Biol 11(1): e1001473.

Kasie Raymann, Louis-Marie Bobay, Thomas G. Doak, Michael Lynch, and Simonetta Gribaldo. 2013. A genomic survey of Reb homologues suggests widespread occurrence of R-bodies in Proteobacteria. G3 3:505-516.

Yu-Wei Wu, Thomas G. Doak, and Yuzhen Ye. 2013. The Gain and Loss of Chromosomal Integron Systems in the Treponema Species. BMC Evolutionary Biology 2013, 13:16.

Quan Zhang, Mina Rho, Haixu Tang, Thomas G. Doak, Yuzhen Ye. 2013. CRISPRs target a diverse collection of invasive mobile genetic elements in human microbiomes. Genome Biology, 14:R40.

Christie AE, Roncalli V, Wu LS, Ganote CL, Doak T, Lenz PH. 2013. Peptidergic signaling in Calanus finmarchicus (Crustacea, Copepoda): In silico identification of putative peptide hormones and their receptors using a de novo assembled transcriptome. Gen Comp Endocrinol. 187C:117-135.

Francesco Catania, Casey L. McGrath, Thomas G. Doak and Michael Lynch. 2013. Spliced DNA sequences in the Paramecium germline: their properties and evolutionary potential.. Genome Biol Evol. 2013 Jun 4.

Quan Zhang, Thomas G. Doak, Mina Rho, Yuzhen Ye. 2013. Expanding the Catalog of Cas Proteins by Metagenomes. In preparation.