Natural genetic variation and incipient speciation (Weigel)

A key question in biology is how organisms adapt to their environment, which eventually leads to the invention of new structures or organs. Many developmental biologists are trying to answer this question by comparing complex structures between distantly related taxa. The difficulties inherent in such an approach were already apparent to Darwin: “To suppose that the eye with all its inimitable contrivances … could have been formed by natural selection, seems, I freely confess, absurd to the highest degree.” An alternative to the study of macroevolutionary events is to investigate variation that occurs within a species or between sister species that can still interbreed.

One of the models that is used in the department to address such questions is phenotypic variation among different strains of Arabidopsis thaliana. The geographical distribution of A. thaliana includes much of the Northern hemisphere, and plants can be found in very different habitats. We have, for example, documented extensive variation in the time to flowering as well as tradeoffs in growth and defense against pathogens, and have been using forward genetics to identify the responsible loci (e.g., Todesco et al., 2010). We have also been looking at other traits, and in the course of these studies, we discovered the first example of a naturally occurring genetic defect associated with a triplet repeat expansion outside humans (Sureshkumar et al., 2009).

To enable the more rapid discovery of functionally relevant variation, we conducted a few years ago a collaboration with Perlegen Sciences to discover a large fraction of common SNPs in 19 wild strains of Arabidopsis thaliana, using array-based whole-genome variation scans (Clark et al., 2007). This work was the basis for the development of a 250k SNP chip. This chip has been used by our collaborators to type hundreds of strains, setting the stage for genome-wide association studies in A. thaliana (Atwell et al., 2010).

As a next step, we have embarked on more extensive genome sequencing using Illumina's Solexa technology. The lab is a leader in the use of short read sequencing, and we have produced  the SHORE pipeline for the analysis of such data. Based on our success with this technology, we initiated a 1001 Genomes Project for A. thaliana; see the project website for more information. The results from the first major phase of the project have just been published (Cao et al., 2011). To understand the patterns of sequence variation in natural strains, it is important to both know the rate and spectrum of spontanenous mutation (Ossowski et al., 2010), and to have outgroup information (Hu et al., 2011). In addition, we are now looking at spontaneous variation in the methylome of A. thaliana (Becker et al., 2011).

Finally, we have discovered multiple cases of gene-flow barriers between wild strains of A. thaliana. Fertilization, hybrid zygote formation and germination of F1 plants are normal at either 16°C or 23°C. At 23°C, F1 hybrid seedlings continue to develop normally, but at 16°C they progressively suffer severe growth defects and are infertile. Our results show that this is caused by dominant interaction of gene products from two unlinked loci, with each parent contributing one incompatible allele at one of the loci. This conforms to predictions of the Bateson-Dobzhansky-Muller model for evolution of post-zygotic isolation. The underlying mechanism is autoimmunity, in which another genome is mistaken as pathogenic (Bomblies et al., 2007). Since our first publication, we have cloned several additional loci that cause incompatibility. One of the cases involves interactions not between unlinked loci, but between divergent alleles at the same locus (Smith et al., 2011).

Key publications

• Atwell, S., Huang, Y., Vilhjálmsson, B., Willems, G., Horton, M., Li, Y., Meng, D., Platt, A., Tarone, A., Jiang, R., Hu, T. T., Muliati, W., Zhang, X., Amer, M. A., Baxter, I., Brachi, B., Chory, J., Dean, C., Debieu, M., de Meaux, J., Ecker, J. R., Faure, N., Kniskern, J., Jones, J. D. G., Michael, T., Nemri, A., Roux, F., Salt, D. E., Tang, C., Todesco, M., Traw, M. B., Weigel, D., Marjoram, P., Borevitz, J. O., Bergelson, J., and Nordborg, M. (2010) Genome-wide association study of 107 phenotypes in a common set of Arabidopsis thaliana inbred lines. Nature 465, 627-631.

• Bomblies, K., Lempe, J., Epple, P., Warthmann, N., Lanz, C., Dangl, J. L., and Weigel, D. (2007) Autoimmune response as a mechanism for a Bateson-Dobzhansky-Muller-type incompatibility syndrome in plants. PLoS Biol. 5, e236.
• Cao, J., Schneeberger, K., Ossowski, S., Günther, T., Bender, S., Fitz, J., Koenig, D., Lanz, C., Stegle, O., Lippert, C., Wang, X., Ott, F., Müller, J., Alonso-Blanco, C., Borgwardt, K., Schmid, K. J., and Weigel, D. (2011) Whole-genome sequencing of multiple Arabidopsis thaliana populations. Nat Genet, published online August 28.

• Clark, R. M., Schweikert, G., Ossowski, S., Zeller, G., Shinn, P., Rätsch, G., Warthmann, N., Fu, G., Hinds, D., Chen, H.-M., Frazer, K., Toomajian, C., Hu, T. T., Huson, D. H., Schölkopf, B., Nordborg, M., Ecker, J. R., and Weigel, D. (2007) Common sequence polymorphisms shaping genetic diversity in Arabidopsis thaliana. Science 317, 338-342.
• Hu, T. T., Pattyn, P., Bakker, E. G., Cao, J., Cheng, J.-F., Clark, R. M., Fahlgren, N., Fawcett, J. A., Grimwood, J., Gundlach, H., Haberer, G., Hollister, J. D., Ossowski, S., Ottilar, R. O., Salamov, A. A., Spannagl, M., Wang, X., Yang, L., Nasrallah, M. E., Bergelson, J., Carrington, J. C., Gaut, B. S., Schmutz, J., Mayer, K. F. X., Van de Peer, Y., Grigoriev, I. V., Nordborg, M., Weigel, D., and Guo, Y.-L. (2011) The Arabidopsis lyrata genome and the basis of rapid genome size change. Nat Genet 43, 476–481.
• Ossowski, S., Schneeberger, K., Lucas-Lledó, J. I., Warthmann, N., Clark, R. M., Shaw, R. G., Weigel, D., and Lynch, M. (2010) The rate and molecular spectrum of spontaneous mutations in Arabidopsis thaliana. Science 327, 92-94.

• Smith, L. M., Bomblies, K., and Weigel, D. (2011) Complex evolutionary events at a tandem cluster of Arabidopsis thaliana genes resulting in a single-locus genetic incompatibility. PLoS Genet 7, e1002164.
• Sureshkumar, S., Todesco, M., Schneeberger, K., Harilal, R., Balasubramanian, S., and Weigel, D. (2009) A genetic defect caused by a triplet repeat expansion in Arabidopsis thaliana. Science 323, 1060-1063.
• Todesco, M., Balasubramanian, S., Hu, T. T., Traw, B. M., Horton, M., Epple, P., Kuhns, C., Sureshkumar, S., Schwartz, C., Lanz, C., Laitinen, R. A. E., Chory, J., Lipka, V., Borevitz, J. O., Dangl, J. L., Bergelson, J., Nordborg, M., and Weigel, D. (2010) Natural allelic variation underlying a major fitness tradeoff in Arabidopsis thaliana. Nature 465, 632-636.

Personnel

Dr. Detlef Weigel weigel@weigelworld.org

Director

Dr. Claude Becker

Postdoctoral fellow (also Small RNA group)

Dr. Jun Cao

Postdoctoral fellow

Dr. Eunyoung Chae

Postdoctoral fellow

Jörg Hagmann

Ph.D. student

Dr. Sang-tae Kim

Postdoctoral fellow

Dr. Dan Koenig

Postdoctoral fellow

Jonas Müller

Ph.D. student

Subhashini Muralidharan

Ph.D. student

Danelle Seymour

Ph.D. student

Dr. Patrice Salomé

Postdoctoral fellow

Dr. Lisa Smith

Postdoctoral fellow (also Small RNA group)

Dr. Marco Todesco

Postdoctoral fellow (also Small RNA group)

Diep Tran

Ph.D. student

Dr. George Wang

Postdoctoral fellow

Dr. Xi Wang

Postdoctoral fellow

Norman Warthmann

Ph.D. student

Maricris Zaidem

Ph.D. student

Current Collaborators

Dr. Daniel Huson

University Tübingen

Dr. Magnus Nordborg

University of South California, US

Dr. Gunnar Rätsch

Friedrich Miescher Laboratory, Tübingen

Dr. Korbinian Schneeberger

Max Planck Institute for Plant Breeding Research, Cologne

Dr. Bernhard Schölkopf

Max Planck Institute for Biological Cybernetics, Tübingen