Limits...
Type III effector diversification via both pathoadaptation and horizontal transfer in response to a coevolutionary arms race.

Ma W, Dong FF, Stavrinides J, Guttman DS - PLoS Genet. (2006)

Bottom Line: We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host.The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele.This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

ABSTRACT
The concept of the coevolutionary arms race holds a central position in our understanding of pathogen-host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among approximately 45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteine-protease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.

Show MeSH

Related in: MedlinePlus

Arms-Race Model(A–C) Star-shaped figures in bacteria represent T3SEs. T1 and T2 are two virulence targets in the host. R is a resistance protein that induces the host-defense response upon recognition of a plant-virulence target modified by a bacterial effector.(A) The pathogen secretes the ancestral HopZ1a T3SE which modifies a host-virulence target and contributes to the disease process.(B) The plant host evolves or acquires an R protein that recognizes the modified target of HopZ1a, and uses this as a cue to induce the defense response, making the plant host resistant to the pathogen.(C) Strong positive selection imposed by the host R protein results in the evolution of modified HopZ T3SEs (e.g., HopZ1b and HopZ1c) or the acquisition of homologs from ecologically similar plant pathogens (e.g., HopZ2 and HopZ3). These T3SEs retain cysteine-protease function, but are not recognized by the R protein, and therefore do not induce a defense response. They may avoid R-protein recognition by either attacking a new virulence target in the host, or by modifying the original target so that it is not recognized by the R protein.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1713259&req=5

pgen-0020209-g007: Arms-Race Model(A–C) Star-shaped figures in bacteria represent T3SEs. T1 and T2 are two virulence targets in the host. R is a resistance protein that induces the host-defense response upon recognition of a plant-virulence target modified by a bacterial effector.(A) The pathogen secretes the ancestral HopZ1a T3SE which modifies a host-virulence target and contributes to the disease process.(B) The plant host evolves or acquires an R protein that recognizes the modified target of HopZ1a, and uses this as a cue to induce the defense response, making the plant host resistant to the pathogen.(C) Strong positive selection imposed by the host R protein results in the evolution of modified HopZ T3SEs (e.g., HopZ1b and HopZ1c) or the acquisition of homologs from ecologically similar plant pathogens (e.g., HopZ2 and HopZ3). These T3SEs retain cysteine-protease function, but are not recognized by the R protein, and therefore do not induce a defense response. They may avoid R-protein recognition by either attacking a new virulence target in the host, or by modifying the original target so that it is not recognized by the R protein.

Mentions: A coevolutionary arms race requires that there be reciprocal selective pressures imposed on two or more species, leading to escalatory adaptations. Escalatory adaptations are those in which evolutionary changes in the pathogen are matched by evolutionary changes in the host, such that the relative balance between these organisms is maintained. In general, these criteria are difficult to meet since they require information about past adaptations and interactions. By combining evolutionary and functional approaches, we have been able to identify a coevolutionary arms race and describe a mechanism for its action (Figure 7). Phylogenetic and population genetic analyses indicate that hopZ1a most closely resembles the ancestral P. syringae hopZ cysteine protease. The ancient bacterium that expressed this T3SE must have attacked a host that lacked a cognate R protein for HopZ1a. Over time, either this ancestral host evolved or acquired the appropriate R protein, or the ancestral pathogen began infecting host species that already had the appropriate R protein. This R protein imposed strong selective pressures on HopZ1a, which resulted in either gene loss, extensive mutational change (pathoadaptation), or the recruitment of homologs from other ecologically similar species by horizontal gene transfer. These new T3SEs retain their cysteine–protease function, but are not all recognized by the R protein that responds to the ancestral HopZ1a. While none of the derived alleles induce a defense response in their respective hosts, the ancestral allele does, indicating that this arms race has selected for alleles that can avoid or suppress host recognition. It is important to note that these evolutionary dynamics likely occurred over many millions of years, and without information regarding the host targets and resistance genes it is impossible to determine the relative importance of host coevolution versus host switching. An important area of future research will be to determine if these T3SEs modify different virulence targets in their hosts, as suggested by the HopZ3 substrate specificity results, or, alternatively, whether the original virulence target is modified in such a way that it does not induce R-protein signaling. Furthermore, it will be very interesting to identify the resistance protein that recognizes these T3SEs, and to perform parallel evolutionary analyses.


Type III effector diversification via both pathoadaptation and horizontal transfer in response to a coevolutionary arms race.

Ma W, Dong FF, Stavrinides J, Guttman DS - PLoS Genet. (2006)

Arms-Race Model(A–C) Star-shaped figures in bacteria represent T3SEs. T1 and T2 are two virulence targets in the host. R is a resistance protein that induces the host-defense response upon recognition of a plant-virulence target modified by a bacterial effector.(A) The pathogen secretes the ancestral HopZ1a T3SE which modifies a host-virulence target and contributes to the disease process.(B) The plant host evolves or acquires an R protein that recognizes the modified target of HopZ1a, and uses this as a cue to induce the defense response, making the plant host resistant to the pathogen.(C) Strong positive selection imposed by the host R protein results in the evolution of modified HopZ T3SEs (e.g., HopZ1b and HopZ1c) or the acquisition of homologs from ecologically similar plant pathogens (e.g., HopZ2 and HopZ3). These T3SEs retain cysteine-protease function, but are not recognized by the R protein, and therefore do not induce a defense response. They may avoid R-protein recognition by either attacking a new virulence target in the host, or by modifying the original target so that it is not recognized by the R protein.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1713259&req=5

pgen-0020209-g007: Arms-Race Model(A–C) Star-shaped figures in bacteria represent T3SEs. T1 and T2 are two virulence targets in the host. R is a resistance protein that induces the host-defense response upon recognition of a plant-virulence target modified by a bacterial effector.(A) The pathogen secretes the ancestral HopZ1a T3SE which modifies a host-virulence target and contributes to the disease process.(B) The plant host evolves or acquires an R protein that recognizes the modified target of HopZ1a, and uses this as a cue to induce the defense response, making the plant host resistant to the pathogen.(C) Strong positive selection imposed by the host R protein results in the evolution of modified HopZ T3SEs (e.g., HopZ1b and HopZ1c) or the acquisition of homologs from ecologically similar plant pathogens (e.g., HopZ2 and HopZ3). These T3SEs retain cysteine-protease function, but are not recognized by the R protein, and therefore do not induce a defense response. They may avoid R-protein recognition by either attacking a new virulence target in the host, or by modifying the original target so that it is not recognized by the R protein.
Mentions: A coevolutionary arms race requires that there be reciprocal selective pressures imposed on two or more species, leading to escalatory adaptations. Escalatory adaptations are those in which evolutionary changes in the pathogen are matched by evolutionary changes in the host, such that the relative balance between these organisms is maintained. In general, these criteria are difficult to meet since they require information about past adaptations and interactions. By combining evolutionary and functional approaches, we have been able to identify a coevolutionary arms race and describe a mechanism for its action (Figure 7). Phylogenetic and population genetic analyses indicate that hopZ1a most closely resembles the ancestral P. syringae hopZ cysteine protease. The ancient bacterium that expressed this T3SE must have attacked a host that lacked a cognate R protein for HopZ1a. Over time, either this ancestral host evolved or acquired the appropriate R protein, or the ancestral pathogen began infecting host species that already had the appropriate R protein. This R protein imposed strong selective pressures on HopZ1a, which resulted in either gene loss, extensive mutational change (pathoadaptation), or the recruitment of homologs from other ecologically similar species by horizontal gene transfer. These new T3SEs retain their cysteine–protease function, but are not all recognized by the R protein that responds to the ancestral HopZ1a. While none of the derived alleles induce a defense response in their respective hosts, the ancestral allele does, indicating that this arms race has selected for alleles that can avoid or suppress host recognition. It is important to note that these evolutionary dynamics likely occurred over many millions of years, and without information regarding the host targets and resistance genes it is impossible to determine the relative importance of host coevolution versus host switching. An important area of future research will be to determine if these T3SEs modify different virulence targets in their hosts, as suggested by the HopZ3 substrate specificity results, or, alternatively, whether the original virulence target is modified in such a way that it does not induce R-protein signaling. Furthermore, it will be very interesting to identify the resistance protein that recognizes these T3SEs, and to perform parallel evolutionary analyses.

Bottom Line: We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host.The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele.This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.

ABSTRACT
The concept of the coevolutionary arms race holds a central position in our understanding of pathogen-host interactions. Here we identify the molecular mechanisms and follow the stepwise progression of an arms race in a natural system. We show how the evolution and function of the HopZ family of type III secreted effector proteins carried by the plant pathogen Pseudomonas syringae are influenced by a coevolutionary arms race between pathogen and host. We surveyed 96 isolates of P. syringae and identified three homologs (HopZ1, HopZ2, and HopZ3) distributed among approximately 45% of the strains. All alleles were sequenced and their expression was confirmed. Evolutionary analyses determined that the diverse HopZ1 homologs are ancestral to P. syringae, and have diverged via pathoadaptive mutational changes into three functional and two degenerate forms, while HopZ2 and HopZ3 have been brought into P. syringae via horizontal transfer from other ecologically similar bacteria. A PAML selection analysis revealed that the C terminus of HopZ1 is under strong positive selection. Despite the extensive genetic variation observed in this family, all three homologs have cysteine-protease activity, although their substrate specificity may vary. The introduction of the ancestral hopZ1 allele into strains harboring alternate alleles results in a resistance protein-mediated defense response in their respective hosts, which is not observed with the endogenous allele. These data indicate that the P. syringae HopZ family has undergone allelic diversification via both pathoadaptive mutational changes and horizontal transfer in response to selection imposed by the host defense system. This genetic diversity permits the pathogen to avoid host defenses while still maintaining a virulence-associated protease, thereby allowing it to thrive on its current host, while simultaneously impacting its host range.

Show MeSH
Related in: MedlinePlus