Abstract

Host-pathogen interactions, especially those involving biotrophic parasites, are complex. Some models related to this system have been published, including the gene-for-gene (GFG) hypothesis, matching-allele (MA) model and guard hypothesis. In the GFG and MA models, the host-pathogen interaction is between products of pathogen genes and host resistance (R) genes. In the guard hypothesis, the host-pathogen interaction includes not only the products of the pathogen genes and host R genes but also products of the pathogenicity target genes in the host. The products of the pathogenicity target genes in the host are very important components of the interaction. To a pathogen, whether a plant is a host or nonhost is determined by the presence or absence of the pathogenicity target genes. Only when a pathogenicity target gene is present and an efficient R gene is not, or when the R gene has been overcome by the pathogen in the course of plant-pathogen coevolution, is the interaction of the plant and the pathogen compatible. Pathogenicity target genes in host plants are constitutively expressed, independently of all induced responses. By silencing or modification of the pathogenicity target gene, the host could be converted into a nonhost, which may possibly generate durable resistance. This represents a potential new direction for crop breeding programmes.

Gene-for-gene hypothesis

During the 1940s and 1950s, Harold Flor studied the inheritance of specific resistance and virulence factors in flax and its fungal pathogen flax rust, defined plant-pathogen interactions genetically, developing the gene-for-gene hypothesis (Flor, 1971). The gene-for-gene hypothesis has been validated by the cloning of many of R and avr genes in recent studies. Based on the gene-for-gene hypothesis, Noel Keen (1990) established a receptor-ligand (elicitor) model. In this model the plant activates defence mechanisms upon R protein (receptor) mediated recognition of pathogen-derived Avr products (ligand). In R proteins that possess extracellular LRRs, a predicted parallel ß-sheet could function as a ligand-binding surface. It has been proposed that the LRR region maybe involved in the specificity of gene-for-gene interactions (Staskawicz et al., 1995). The interaction of plant-pathogen recognition involved in gene-for-gene specificity related to receptor-ligand (elicitor) model was verified by the recognition event between the product of the avrPto gene of Pseudomonas syringae pv. tomato and the product of the Pto R gene of tomato, a serine/threonine protein kinase (Scofield et al., 1996; Tang et al., 1996). Another specific R-Avr protein interaction of AvrPita (an avr product from the fungus Magnaporthe grisea) and the R gene product Pita (an NB-LRR protein) from rice (Jia et al., 2000), also supports the receptor-ligand (elicitor) model. However, it should be noted that the direct interactions of R genes with avirulence genes are not the common mechanism, instead most Avr proteins are likely indirectly detected by R proteins (Xia, 2004). For example, Dixon and colleague had investigated whether Cf-9 and Avr9 directly interact with each other. These experiments had failed to reveal a direct interaction between Avr9 and Cf-9, suggesting that other factors are required for Avr9 perception (Dixon et al., 2000). Luderer et al. (2002) also provided a convincing lack of evidence for an interaction between the products of these genes using a variety of sophisticated binding assays under different experimental conditions.

Matching-allele model

Although the receptor-ligand model is the biochemical interpretation of the gene-for-gene hypothesis (van der Biezen & Jones, 1998), based on the elicitor-receptor model, Frank (1993) developed a matching-allele model where the concept is distinct from the gene-for-gene hypothesis. Agrawal and Lively (2002) discussed the controversy between the gene-for-gene and matching-allele models, indicated that these two models represent two ends of one continuum. The gene-for-gene model favoured by plant pathologists represents one end of a continuum, where a very broad host range is expected to occur in one pathogen genotype. The matching alleles model, favored by invertebrate zoologists, represents the opposite end of the same continuum, where an exact genetic match is required for resistance. Indeed the matching-allele model and the classical gene-for-gene interaction of plants and pathogens are distinct from each other. In the matching-allele model each parasite genotype functions as either an avirulence allele or a virulence allele depending on the host genotype. By contrast, the gene-for-gene system always has a universal virulence allele that can attack all host genotypes. Similarly, each host genotype in the matching-allele model functions as either a resistance or a susceptibility allele depending on the parasite genotype. The classical gene-for-gene system always has a universal susceptible genotype that can be attacked by all parasite genotypes (Frank, 1993). In population genetics, the matching-allele model typically produces allele-frequency dynamics characterized by shorter periods and higher amplitudes. The matching-allele model generates the selection for recombination whereas the gene-for-gene model does not (Agrawal & Lively, 2002; Agrawal & Lively, 2003; Parker, 1994). Higher levels of local adaptation are observed under the matching-allele model than under the gene-for-gene model (Agrawal & Lively, 2003; Lively, 1999).

Interestingly, Agrawal and Lively (2003) developed a two-step detection and eradication model. This model incorporates 'matching-allele' genetics for detection and 'gene-for-gene' genetics for eradication. The detection step is governed by matching-allele loci whereas the eradication step is governed by gene-for-gene loci. The first detection step is that if a parasite matches its host at the relevant loci, then the parasite is able to live undetected within its host; if a parasite does not match its host then the host detects that a parasite is present. The second eradication step is that the host attempts to remove an identified parasite. If the host has at least one resistance allele for which the parasite has an avirulence allele at the corresponding locus, the host is able to eliminate the parasite. But in the two-step model, even though inherently contains both matching-allele and gene-for-gene loci, the population genetic dynamics of this host-parasite system often appear as though only one of the two types is present (Agrawal & Lively, 2003).

Guard hypothesis

Plant R proteins are postulated to provide a surveillance system that can detect Avr determinants from diverse viral, prokaryotic, and eukaryotic pathogens. The guard hypothesis provides a reasonable conceptual framework to explain the mechanisms of plant-pathogen interaction. In the guard hypothesis, Avr products interact with host proteins to promote disease, and that R proteins ''guard'' these host components and initiate Avr-dependent plant defense responses (Dangl & Jones, 2001). The guard hypothesis predicts that for each R protein there is both a corresponding pathogen Avr product and a host target. Such a model would explain the dual recognition capacity of some NB-LRR proteins such as RPM1 and Mi-1 if they ''guard'' the same host component targeted by unrelated Avr products. Evolutionary mechanisms sustaining R gene diversity are essential for the plant to be able to detect distinct pathogen (a)virulence products that target R protein-''guarded'' host components (Dixon et al., 2000).

There are two logical extensions of the guard hypothesis. First, a given R protein could, in principle, respond to the presence of two or more unrelated avirulence effector proteins that presumably are targeting the same host plant protein. The second important logical extension of the guard hypothesis is that a host protein complex that is a common target of pathogen virulence functions might be guarded and protected from avirulence effectors by more than one R protein (Mackey et al., 2003). Arabidopsis RIN4 plays a role in the plant defense response, which is a key bacterial virulence target that is guarded by the resistance (R) protein RPM1. Two recent studies suggest that another R protein, RPS2, also guards RIN4. Bacterial avirulence (Avr) effectors AvrB, AvrRpm1, and AvrRpt2 target and alter this key protein. R proteins RPM1 and RPS2 recognize and guard the altered status and initiate a defense-signaling response (Mackey et al., 2003; Marathe & Dinesh-Kumar, 2003).

Pathogenicity target genes

Ethylene synthesis is required for wild-type disease development in tomato leaves. The evolution of ethylene occurs concomitantly with the progression of disease symptoms in response to many virulent pathogen infections in plants (Lund et al., 1998). In the plant-pathogen coevolution, pathogen virulence genes and pathogenicity target genes in its host are evolved simultaneously. Ethylene possibly is related to the pathogenicity target genes. Tomato pretreated with ethylene showed a decreased susceptibility toward Botrytis cinerea (Diaz et al., 2002). The overdose ethylene blocked the ethylene synthesis pathway, inhibited a serious of genes expression, included one what acted as the pathogenicity target gene. Pathogen-encoded (a)virulence factors could interact with host proteins to modify their functions to access nutrients or to suppress defense mechanisms(Dixon et al., 2000). The interaction of pathogen virulence genes with pathogenicity target genes in plant may cause disease; the interaction of pathogen avirulence genes with plant R genes will cause resistance. From an evolutionary perspective, the selection pressure exerted by the pathogens, which evolved the pathogenicity factors necessary to overcome nonhost resistance, may have driven the development of host resistance (Heath, 1981), which indicated that the pathogenicity target genes evolved maybe earlier than the R genes at the species level. R gene-mediated resistance, at least in crop plants, often is overcome rapidly in the field, and it has been proposed that R genes and their corresponding avr genes are locked in a relentless cycle of coevolution (Ashfield et al., 2004). This means after R gene had been generated, the new virulence gene would be evolved and this cycle is continued. In recent studies, some pathogenicity target genes or related genes have been identified. Mayda et al. (2000) isolated a disease susceptibility regulator recessive mutant that is not affected in salicylic acid metabolism and shows normal expression of pathogenesis-related (PR) genes after pathogen attack. Vogel et al. (2000; 2002) identified a novel collection of mutants affecting genes required for a compatible interaction between a plant and a biotrophic pathogen. In these mutants, resistance to Powdery Mildew does not require the activation of well-described defense pathways. In their research, the authors indicated that for obvious reasons, a tremendous amount of research has focused on identifying the plant genes involved in mediating resistance to a diverse array of pathogens. In contrast, little is known about the plant components of compatible plant-microbe interactions. The best-characterized examples of host susceptibility factors are plant metabolites that induce bacterial genes and or serve as chemoattractants. For example, flavonoids produced by plant roots induce nodulation genes in Rhizobium spp., the first step in the formation of a nitrogen-fixing root nodule. Another susceptibility factor, acetosyringone, is produced by wounded plant cells and plays an important role in the development of crown gall disease caused by Agrobacterium tumefaciens (Vogel & Somerville, 2000). In human, a collagen type I alpha2 (COL1A2) is the susceptible gene for intracranial aneurysms (Yoneyama et al., 2004). In animal cells, vitronectin protein, a component of extracellular matrix, is utilized as a specific receptor by several pathogenic bacterial strains (Paulsson & Wadstrom, 1990).

The nature of the pathogenicity target genes and resistant R genes are completely different. The R genes are resistance genes, which can cause HR. Presence or absence of an efficient R gene creates a bad or good growth condition for pathogen. In some cases, R genes are often quickly defeated by pathogens. The pathogenicity target genes possibly are constitutively expressed, independently of pathogen induced responses. Presence or absence of the pathogenicity target genes make the pathogen infection can or cannot. Only in the long course of coevolution, the pathogen has the possibility to adapt itself to certain plants and makes the plants to be the host, and the pathogenicity target genes have been evolved. The pathogenicity target genes evolved earlier than R genes at the species level. Many R gene products share common structural modules such as a nucleotide-binding site and leucine-rich repeat domain, and pathogenicity target gene products do not. Figure 1 is a pathogenicity target gene model for the plant-pathogen interaction. The pathogenicity target genes are crucial components for the nonhost resistance.

Application of the pathogenicity target genes in breeding programmes

Although substantial progress in plant disease resistance research has been achieved, in some aspects and to some extent, our global food supply system is threatened even more (McDowell & Woffenden, 2003; Moffat, 2001). Much time, money and effort have been expended on the identification, characterization and introgression of many hundreds of host disease resistant R genes. However, the resistance conferred by these genes has in the majority of cases been ephemeral. The nonhost resistance is highly effective and durable, and hence it is often suggested that the mechanisms of nonhost resistance can be exploited to generate resistance crop plants (Thordal-Christensen, 2003). Race-specific resistance genes often are overcome very quickly in the field by rapid evolution of the pathogen population. In contrast, the nonhost resistance genes represent a potential source of durable resistance for breeding programme (Neu et al., 2003). In total, eleven R genes for Phytophthora infestans had been introduced from Solanum demissum into potato. In nature, numerous races of P. infestans have evolved that is able to infect plants containing these R genes (Vleeshouwers et al., 2000). The nonhost resistance is a durable resistance. Pathogens have rarely altered their host species range over recorded history (Heath, 2000). It does not like R genes what is easy to be overcome by pathogens, the pathogenicity target gene is not easy to be evolved and overcome. Pathogens adapt nonhost and make their target genes evolved, it will need a long coevolution course. Of course, due to the pathogenicity target genes are possibly constitutively expressed, it is difficult to isolate and apply it than that of specific expressed or induced genes. But this is not the key point. The most important is that we should realize the importance of the application of the pathogenicity target genes in breeding programmes. Silencing or modifying of the pathogenicity target genes will possibly make the host converted into a nonhost, and generate a durable resistance-this will be a new direction for crop and animal breeding programmes, and it will create a safe sustainable food supply system. We do not need to worry about the transgenetic food again, because it is not necessary to introduce foreign genes by genetic engineering, just create a mutant what the pathogenicity target genes are modified that is enough.

References

Agrawal A, Lively CM, 2002. Infection genetics, gene-for-gene versus matching-alleles models and all points in between. Evolutionary Ecology Research 4, 79-90.

Agrawal AF, Lively CM, 2003. Modelling infection as a two-step process combining gene-for-gene and matching-allele genetics. Proceedings of the Royal Society of London Series B-Biological Sciences 270, 323-334.

Ashfield T, Ong LE, Nobuta K, Schneider CM, Innes RW, 2004. Convergent evolution of disease resistance gene specificity in two flowering plant families. Plant Cell 16, 309-318.

Dangl JL, Jones JD, 2001. Plant pathogens and integrated defence responses to infection. Nature 411, 826-833.

Diaz J, ten Have A, van Kan JA, 2002. The role of ethylene and wound signaling in resistance of tomato to Botrytis cinerea. Plant Physiol 129, 1341-1351.

Dixon MS, Golstein C, Thomas CM, van der Biezen EA, Jones JDG, 2000. Genetic complexity of pathogen perception by plants, The example of Rcr3, a tomato gene required specifically by Cf-2. Proceedings of the National Academy of Sciences of the United States of America 97, 8807.

Flor HH, 1971. Current status of the gene-for-gene concept. Annual Review of Phytopathology, 275-296.

Frank SA, 1993. Specificity Versus Detectable Polymorphism in Host-Parasite Genetics. Proceedings of the Royal Society of London Series B-Biological Sciences 254, 191-197.

Heath MC, 1981. Resistance of Plants to Rust Infection. Phytopathology 71, 971-974.

Heath MC, 2000. Nonhost resistance and nonspecific plant defenses. Current Opinion in Plant Biology 3, 315-319.

Jia Y, McAdams SA, Bryan GT, Hershey HP, Valent B, 2000. Direct interaction of resistance gene and avirulence gene products confers rice blast resistance. EMBO Journal 19, 4004-4014.

Keen NT, 1990. Gene-for-gene complementarity in plant-pathogen interactions. Annual Review of Genetics 24, 447-463.

Lively CM, 1999. Migration, virulence, and the geographic mosaic of adaptation by parasites. American Naturalist 153, S34-S47.

Luderer R, Takken FL, de Wit PJ, Joosten MH, 2002. Cladosporium fulvum overcomes Cf-2-mediated resistance by producing truncated AVR2 elicitor proteins. Molecular Microbiology 45, 875-884.

Lund ST, Stall RE, Klee HJ, 1998. Ethylene regulates the susceptible response to pathogen infection in tomato. Plant Cell 10, 371-382.

Mackey D, Belkhadir Y, Alonso JM, Ecker JR, Dangl JL, 2003. Arabidopsis RIN4 is a target of the type III virulence effector AvrRpt2 and modulates RPS2-mediated resistance. Cell 112, 379-389.

Marathe R, Dinesh-Kumar SP, 2003. Plant defense, One post, multiple guards?! Molecular Cell 11, 284-286.

Mayda E, Mauch-Mani B, Vera P, 2000. Arabidopsis dth9 mutation identifies a gene involved in regulating disease susceptibility without affecting salicylic acid-dependent responses. Plant Cell 12, 2119-2128.

McDowell JM, Woffenden BJ, 2003. Plant disease resistance genes, recent insights and potential applications. Trends in Biotechnology 21, 178-183.

Moffat AS, 2001. Finding new ways to fight plant diseases. Science 292, 2270-2273.

Neu C, Keller B, Feuillet C, 2003. Cytological and molecular analysis of the Hordeum vulgare-Puccinia triticina nonhost interaction. Molecular Plant-Microbe Interactions 16, 626-633.

Parker MA, 1994. Pathogens and Sex in Plants. Evolutionary Ecology 8, 560-584.
Paulsson M, Wadstrom T, 1990. Vitronectin and type-I collagen binding by Staphylococcus aureus and coagulase-negative staphylococci. FEMS Microbiol Immunol 2, 55-62.

Scofield SR, Tobias CM, Rathjen JP, Chang JH, Lavelle DT, Michelmore RW,
Staskawicz BJ, 1996. Molecular basis of gene-for-gene specificity in bacterial speck disease of tomato. Science 274, 2063-2065.

Staskawicz BJ, Ausubel FM, Baker BJ, Ellis JG, Jones JDG, 1995. Molecular-Genetics of Plant-Disease Resistance. Science 268, 661-667.

Tang XY, Frederick RD, Zhou JM, Halterman DA, Jia YL, Martin GB, 1996. Initiation of plant disease resistance by physical interaction of AvrPto and Pto kinase. Science 274, 2060-2063.

Thordal-Christensen H, 2003. Fresh insights into processes of nonhost resistance. Current Opinion in Plant Biology 6, 351-357.

van der Biezen EA, Jones JDG, 1998. Plant disease-resistance proteins and the gene-for-gene concept. Trends in Biochemical Sciences 23, 454-456.

Vleeshouwers V, van Dooijeweert W, Govers F, Kamoun S, Colon LT, 2000. The hypersensitive response is associated with host and nonhost resistance to Phytophthora infestans. Planta 210, 853-864.

Vogel J, Somerville S, 2000. Isolation and characterization of powdery mildew-resistant Arabidopsis mutants. Proceedings of the National Academy of Sciences of the United States of America 97, 1897-1902.

Vogel JP, Raab TK, Schiff C, Somerville SC, 2002. PMR6, a pectate lyase-like gene required for powdery mildew susceptibility in Arabidopsis. Plant Cell 14, 2095-2106.

Xia Y, 2004. Proteases in pathogenesis and plant defence. Cell Microbiology 6, 905-913.

Yoneyama T, Kasuya H, Onda H, Akagawa H, Hashiguchi K, Nakajima T, Hori T,
Inoue I, 2004. Collagen type I alpha 2 (COL1A2) is the susceptible gene for intracranial aneurysms. Stroke 35, 443-448.