Richard M. Clark
Assistant Professor of Biology
B.A. Kenyon College
Ph.D. Stanford University
Richard Clark's Lab Page
Richard Clark's PubMed Literature Search
Research
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 agriculture (e.g., DNA methylation and flowering time, respectively).
As a first 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 at the Max Planck Institute in Tuebingen, Germany, I identified over 1 million single nucleotide polymorphisms (SNPs), as well as thousands of deletions, in a global Arabidopsis population sample. This dense polymorphism data, collected with microarray methods, has become the basis for establishing a haplotype map (HapMap) resource for the species. An end goal of creating this resource is to enable the application of whole genome association (WGA) studies to quickly describe quantitative trait variation in the species. Beyond establishing the resource, we identified families of genes and sequence types that show extreme variation, potentially as a result of selection. As for human, such genes were enriched for those involved in response to pathogens.
Despite the large number of polymorphisms we discovered in our array studies, we identified only a fraction of all polymorphisms in given strains. To extend this work, I am now using so-called “second-generation” sequencing techniques (e.g., the Illumina/Solexa method) to more fully describe variation in Arabidopsis and other genomes. These ongoing studies will be expanded in future to characterize the effect of sequence variation on gene expression, and to understand how both genotype and environment alter regulatory networks to lead to phenotypic differences between strains and individuals.
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 methodology and biological insights from Arabidopsis to plant or animal species of environmental and economic importance.
References
1. 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
2. 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
3. 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
4. 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
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
6. 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
7. 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
8. Clark RM, Wagler TN, Quijada P, Doebley J (2006) A distant upstream enhancer at the maize domestication gene tb1 has pleiotropic effects on plant and inflorescent architecture. Nature Genetics 38(5):594-7
9. Clark RM, Tavaré S, Doebley J (2005) Estimating a nucleotide substitution rate for maize from polymorphism at a major domestication locus. Molecular Biology and Evolution 22(11):2304-12
10. Clark RM, Linton E, Messing J, Doebley JF (2004) Pattern of diversity in the genomic region near the maize domestication gene tb1. Proc Natl Acad Sci USA 101(3):700-7


