Associate Professor of Biology
B.A. Kenyon College
Ph.D. Stanford University
Richard Clark's Lab Page
Richard Clark's PubMed Literature Search
Molecular Biology Program
Genetics and Gene Expression
We are interested in understanding the effect of genotype and environment on phenotypic variation at both molecular and whole organism scales. To do this, we employ the reference plant, Arabidopsis thaliana (thale cress). Arabidopsis is an excellent choice for our studies, as exceptional molecular-genetic resources are available. Moreover, thousands of wild inbred strains have been collected, and harbor extensive phenotypic variation for traits of relevance to both medicine and ecology/agriculture (e.g., DNA methylation and flowering time).
As a step to understand the genetic contribution to phenotype, as well as the genotype by environment interaction, I began work as a postdoc to systematically describe the complement of common sequence polymorphisms in the Arabidopsis population. Working with colleagues, we initially identified more than a million SNPs in Arabidopsis using microarray methods, and as part of several ongoing collaborations we have extended these initial studies with high-throughput sequencing to describe structural variation as well (our ultimate goal is complete sequence information). More recently, a central focus of the lab is to generate and analyze deep transcriptome data for hundreds of sequenced Arabidopsis strains (cDNA sequencing, also called RNA-seq). Here, our goals are several. The first is to provide experimental data to support genome re-annotation independent of the reference sequence. This is critical in most organisms, but especially in plants like Arabidopsis, as levels of intra-specific variation are high, and we have found that many genes differ markedly in structure (or presence or absence) between strains. A second goal is to use the well-annotated genomes to understand the evolution of gene structure and function, and in turn how genetic differences impact gene expression and expression networks to underlie variation in organismal phenotypes. To answer these questions, and along with collaborators, we are performing these studies with sufficient sample sizes to enable comprehensive, genome-wide association mapping of both molecular phenotypes and organismal traits.
Since we address fundamental questions about the relationships between sequence variation, complex traits, and evolution, our work should generalize well to other species. A long-term goal is the transfer of detailed methods and biological insights from Arabidopsis to plant or animal species of environmental and economic importance.
- Van Leeuwen T, Demaeght P, Osborne EJ, Dermauw W, Gohlke S, Nauen R, Grbic M, Tirry L, Merzendorfer H, Clark RM (2012) Population bulk segregant mapping uncovers resistance mutations and the mode of action of a chitin synthesis inhibitor in arthropods. Proc Natl Acad Sci U S A, Epub ahead of print
- Grbić M, Van Leeuwen T, Clark RM, Rombauts S, Rouzé P, Grbi? V, Osborne EJ, Dermauw W, Ngoc PC, Orteg F, Hernández-Crespo P, Diaz I, Martinez M, Navajas M, Sucena E, Magalhães S, Nagy L, Pace RM, Djuranovi? S, Smagghe G, Iga M, Christiaens O, Veenstra JA, Ewer J, Villalobos RM, Hutter JL, Hudson SD, Velez M, Yi SV, Zeng J, Pires-daSilva A, Roch F, Cazaux M, Navarro M, Zhurov V, Acevedo G, Bjelica A, Fawcett JA, Bonnet E, Martens C, Baele G, Wissler L, Sanchez-Rodriguez A, Tirry L, Blais C, Demeestere K, Henz SR, Gregory TR, Mathieu J, Verdon L, Farinelli L, Schmutz J, Lindquist E, Feyereisen R, Van de Peer Y (2011) The genome of Tetranychus urticae reveals herbivorous pest adaptations. Nature, 479(7374):487-92
- Gan X, Stegle O, Behr J, Steffen JG, Drewe P, Hildebrand KL, Lyngsoe R, Schultheiss SJ, Osborne EJ, Sreedharan VT, Kahles A, Bohnert R, Jean G, Derwent P, Kersey P, Belfield E, Harberd N, Kemen E, Kover P, Toomajian C, Clark RM, Rätsch M, Mott R (2011) Multiple reference genomes and transcriptomes for Arabidopsis thaliana. Nature, 477(7365):419-23
- Hu TT, Pattyn P, Bakker EG, Cao J, Cheng JF, Clark RM, Fahlgren N, Fawcett JA, Grimwood J, Gundlach H, Haberer G, Hollister JD, Ossowski S, Ottilar RP, Salamov AA, Schneeberger K, Spannagl M, Wang X, Yang L, Nasrallah ME, Bergelson J, Carrington JC, Gaut BS, Schmutz J, Mayer KF, Van de Peer Y, Grigoriev IV, Nordborg M, Weigel D, Guo YL (2011) The Arabidopsis lyrata genome sequence and the basis of rapid genome size change. Nat Genet, 43(5):476-81
- Ossowski S, Schneeberger K, Lucas-Lledó JI, Warthmann N, Clark RM, Shaw RG, Weigel D, Lynch M (2010) The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana. Science, 327(5961):92-4
- McNally KL, Childs KL, Bohnert R, Davidson RM, Zhao K, Ulat VJ, Zeller G, Clark RM, Hoen DR, Bureau TE, Stokowski R, Ballinger DG, Frazer KA, Cox DR, Padhukasahasram B, Bustamante CD, Weigel D, Mackill DJ, Bruskiewich RM, Rätsch G, Buell CR, Leung H, Leach JE (2009) Genomewide SNP variation reveals relationships among landraces and modern varieties of rice. Proc Natl Acad Sci U S A, 106(30): 12273-8
- Ossowski S, Schneeberger K, Clark RM, Lanz C, Warthmann N, Weigel D (2008) Sequencing of natural strains of Arabidopsis thaliana with short reads. Genome Research, 18:2024-2033
- Zeller G, Clark RM, Schneeberger K, Bohlen A, Weigel D, Rätsch G (2008) Detecting polymorphic regions in Arabidopsis thaliana with resequencing microarrays. Genome Research, 18(6):918-29
- Weber A, Clark RM, Vaughn L, Sánchez-Gonzalez JJ, Yu J, Yandell BS, Bradbury P, Doebley J (2007) Major regulatory genes in maize contribute to standing variation in teosinte (Zea mays ssp. parviglumis). Genetics, 177(4):2349-59
- Kim S, Plagnol V, Hu TT, Toomajian C, Clark RM, Ossowski S, Ecker JR, Weigel D, Nordborg M (2007) Recombination and linkage disequilibrium in Arabidopsis thaliana. Nature Genetics, 39(9):1151-5
- Clark RM, Schweikert G, Toomajian C, Ossowski S, Zeller G, Shinn P, Warthmann N, Hu TT, Fu G, Hinds DA, Chen H, Frazer KA, Huson DH, Scholkopf B, Nordborg M, Rätsch G, Ecker JR, Weigel D (2007) Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana. Science, 317(5836):338-42
- Tang C, Toomajian C, Sherman-Broyles S, Plagnol V, Guo YL, Hu TT, Clark RM, Nasrallah JB, Weigel D, Nordborg M (2007) The evolution of selfing in Arabidopsis thaliana. Science, 317(5841):1070-2
- Balasubramanian S, Sureshkumar S, Agrawal M, Michael TP, Wessinger C, Maloof JN, Clark R, Warthmann N, Chory J, Weigel D (2006) The PHYTOCHROME C photoreceptor gene mediates natural variation in flowering and growth responses of Arabidopsis thaliana. Nature Genetics, 38(6):711-5