Molecular Genetics of Plant Disease Resistance Brian J. Staskawicz,* Frederick M. Ausubel, Barbara J. Baker, Jeffrey G. Ellis, Jonathan D. G. Jones Plant breeders have used disease resistance genes (R genes) to control plant disease since the turn of the century. Molecular cloning of R genes that enable plants to resist a diverse range of pathogens has revealed that the proteins encoded by these genes have several features in common. These findings suggest that plants may have evolved com- mon signal transduction mechanisms for the expression of resistance to a wide range of unrelated pathogens. Characterization of the molecular signals involved in pathogen recognition and of the molecular events that specify the expression of resistance may lead to novel strategies for plant disease control. Plants, like animals, are continually ex- posed to pathogen attack. Because plants lack a circulatory system and antibodies, they have evolved a defense mechanism that is distinct from the vertebrate immune system (1). In contrast to animal cells, each plant cell is capable of defending itself by means of a combination of constitutive and induced defenses (2). Knowledge about the genetic and biochemical basis of plant dis- ease resistance has accumulated since the turn of the century, when plant breeders first recognized that resistance was often con- trolled by Mendelian genes (3). The dem- onstration that plants have geographical centers of origin (4) and have co-evolved with their pathogens was a pivotal discovery for plant breeders and has led to the use of interspecific hybrids between crops and their wild relatives as sources of resistant germ plasm (5). Until 1992, however, no plant R gene had been cloned and charac- terized at the molecular level (6). Since then, R genes from several plant species Avirulent pathogen Pathogenests Virulent pathogen W.... have been cloned; this constitutes a major advance for molecular plant biology and may lead to the development of novel meth- ods for disease control. Plant Responses to Pathogen Attack The range of phytopathogenic organisms that attack plants is diverse and includes viruses, mycoplasma, bacteria, fungi, nema- todes, protozoa, and parasites (7). Each has a unique mode of pathogenicity. Despite the vast array of potential phytopathogens, resis- tance (lack of susceptibility) is the rule and susceptibility is the exception. Why one pathogen can cause disease in one plant but not in other plants a phenomenon often termed nonhost resistance-remains an im- portant unsolved problem in plant pathology. Resistance to a pathogen is manifested in a variety of ways and is often correlated with a hypersensitive response (HR), local- ized induced cell death in the host plant at Virulent pathogen Plant host cell DISEASE a Fig. 1. Gene-for-gene interactions specify plant disease resistance. Resistance is only expressed when a plant that contains a specific R gene recognizes a pathogen that has the corresponding avirulence gene (upper left panel). All other combinations lead to lack of recognition by the host, and the result is disease. Green represents hypersensitive response; yellow represents susceptibility to disease. SCIENCE * VOL. 268 * 5 MAY 1995 the site of infection (8). Although the mo- lecular mechanism is obscure, HR is thought to be responsible for the limitation of pathogen growth. Resistance does not always invoLve visible HR, which may re- flect either HR limited to individual plant cells or other uncharacterized defense mechanisms. Alternatively, the pathogen could lack a specific pathogenicity function required to cause disease in the host, or the host could lack a specific "susceptibility" factor. Although this review concerns the molecular basis of HR-mediated resistance, the elucidation of the mechanisms involved in nonhost resistance without HR may be an important component of future attempts to control plant disease. The genetic basis of HR-mediated dis- ease resistance was first clarified by Flor, who demonstrated that the resistance of flax to the fungal pathogen Melampsora lini was a consequence of the interaction of paired cognate genes in the host and the pathogen (9). His work provided the theoretical basis for the gene-for-gene hypothesis of plant- pathogen interactions and for the molecular cloning of pathogen avirulence (avr) genes and their corresponding plant R genes. An avr gene gives the pathogen an avirulent phenotype on a host plant that carries the corresponding R gene (Fig. 1) (10). In gene- for-gene interactions, the induction of the plant defense response that leads to HR is initiated by the plant's recognition of spe- cific signal molecules (elicitors) produced by the pathogen; these elicitors are encoded directly or indirectly by avirulence genes, and R genes are thought to encode receptors for these elicitors. Elicitor recognition acti- vates a cascade of host genes that leads to HR and inhibition of pathogen growth (1 1). Gene-for-gene systems involving HR have been described for pathosystems in- volving intracellular obligate pathogens (vi- B. J. Staskawicz is in the Department of Plant Biology, University of California, Berkeley, CA 94720, USA. F. M. Ausubel is in the Department of Genetics, Harvard Medical School, Boston, MA 02115, USA, and Department of Mo- lecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA. B. J. Baker is at the Plant Gene Expres- sion Center, Agricultural Research Service, U.S. Depart- ment of Agriculture, Albany, CA 94710, USA, and Depart- ment of Plant Biology, University of California, Berkeley, CA 94720, USA. J. G. Ellis is at the CSIRO Division of Plant Industry and Cooperative Research Centre for Plant Sci- ence, Post Office Box 1600, Canberra, A.C.T., Australia. J. D. G. Jones is at the Sainsbury Laboratory, John Innes Centre, Norwich Research Park, Colney Lane, Norwich NR4 7UH, UK. *To whom correspondence should be addressed. E-mail: stask~garnet.berkeley.edu 661 wilaoworAmm~ m 1 Plant hnst cell1 am~ a awe, on June 26, 2007 www.sciencemag.org Downloaded from