Defended to the Nines: 25 Years of Resistance Gene Cloning Identifies Nine Mechanisms for R Protein Function

Abstract

Plants have many, highly variable resistance (R) gene loci, which provide resistance to a variety of pathogens. The first R gene to be cloned, maize (Zea mays) Hm1, was published over 25 years ago, and since then, many different R genes have been identified and isolated. The encoded proteins have provided clues to the diverse molecular mechanisms underlying immunity. Here, we present a meta-analysis of 314 cloned R genes. The majority of R genes encode cell surface or intracellular receptors, and we distinguish nine molecular mechanisms by which R proteins can elevate or trigger disease resistance: direct (1) or indirect (2) perception of pathogen-derived molecules on the cell surface by receptor-like proteins and receptor-like kinases; direct (3) or indirect (4) intracellular detection of pathogen-derived molecules by nucleotide binding, leucine-rich repeat receptors, or detection through integrated domains (5); perception of transcription activator-like effectors through activation of executor genes (6); and active (7), passive (8), or host reprogramming-mediated (9) loss of susceptibility. Although the molecular mechanisms underlying the functions of R genes are only understood for a small proportion of known R genes, a clearer understanding of mechanisms is emerging and will be crucial for rational engineering and deployment of novel R genes.

Figure 1.

Analysis of Molecular Mechanisms Underpinning R Genes. A near-comprehensive literature search resulted in a database of R genes conferring immunity to a wide range of plant pathogens (Supplemental Data Set 1). This list was filtered to remove duplicates: R genes that code for receptors that perceive pathogen components were counted only once if this component is conserved between pathogens. By contrast, if an R gene codes for a receptor that perceives structurally or sequence unrelated pathogen-derived components, these were counted multiple times. Furthermore, alleles of R genes with slightly different recognition spectra were counted as multiple R genes, as were paralogs within species and orthologs in different species which are shown to be involved in immunity. Loss-of-susceptibility R genes that can act against several pathogens through an identical mechanism were counted only once. In addition, R genes that were shown to induce enhanced disease resistance when taken outside of their native context were removed, as were engineered R genes. Finally, some genes that are involved in autoimmunity resemble R genes, but these were not included unless these were proven to be involved in immunity against pathogens. (A) A timeline summarizing the increased knowledge regarding R genes. The identified mechanisms were plotted cumulatively over time, with some of the milestones added. The date of the first cloned R gene was taken in case multiple host components are involved or the underlying molecular mechanism was elucidated later. These R genes were grouped according to the proposed mechanism of function as we understand it today. (B) All identified R genes were grouped according to their proposed mechanism. (C) The identified R genes were grouped by pathogen which they act against and colored by the molecular mechanism by which they function. (D) The identified R genes were grouped by host species carrying them and colored by the molecular mechanism by which they function. Colors are explained in (B).

Figure 2.

Nine Molecular Mechanisms Underpinning R Gene Functions. Illustration of direct (1) and indirect (2) recognition at the cell surface; four different intracellular perception mechanisms (3–6); and three loss-of-susceptibility mechanisms (7–9). PAMPs and effectors are colored in purple, indirect receptors in light green, and direct receptors in dark green.