REVIEW RESEARCH suggests that the disease may have been vectored from this region in increased ozone,have been shown to have the opposite effect (for contaminated soil. example,in Puccinia recondita"). Evidence for the idea that climate change has an impact on the Accelerated evolution of virulence in pathogenic fungi dynamics and distribution of animal-infecting fungi is less clear-cut than Human activities are not only associated with the dispersal of patho- that in relation to plant-infecting fungi and,although arguments have genic fungi,they also interact with key fungal characteristics,such as been made that warming trends may have contributed to the emergence habitat flexibility,environmental persistence and multiple reproductive of B.dendrobatidis in Central America and Europe,there is active modes,to cause the emergence of disease.Importantly,many fungi are debate about these conclusions Regardless,it is clear that the disease flexible in their ability to undergo genetic recombination,hybridization state,chytridiomycosis,is linked to environmental factors;regional or horizontal gene transfer causing the clonal emergence of patho- climate warming can increase the local range of the pathogens and genic lineages but also allowing the formation of novel genetic diversity disease risk is inversely related to rates of deforestation.Correlations leading to the genesis of new pathogensReproductive barriers in between ecosystem change and a rise in infection by opportunistic patho- fungi are known to evolve more rapidly between sympatric lineages that gens has been proposed to account for the occurrence of coral reef are in the nascent stages of divergence than between geographically declines worldwide.For example,disease caused by a variety of microbes separated allopatric lineages,in a process known as reinforcements threatens hard corals to the extent that two of the most abundant As a consequence,anthropogenic mixing of previously allopatric fungal Caribbean reef-builders (staghorn and elkhorn corals)are now listed lineages that still retain the potential for genetic exchange can drive under the US Endangered Species Act.Across varied reef systems,the rapid macroevolutionary change.Although many hybrids are inviable occurrence of warm-temperature anomalies leading to bleaching events owing to genome incompatibilities,large phenotypic leaps can be is associated with increases in disease caused by opportunistic pathogens achieved by the resulting 'hopeful monsters',leading to host jumps such as A.sydowir.In an allied colonial system,colony collapse disorder and increased virulence'.Such mechanisms are thought to drive the has resulted in steep declines of the European honeybee Apis mellifera in formation of new pathotypes in plant pathogens,and oomycetes as Europe and North America.These losses seem to be influenced by a well as fungi exhibit the genesis of new interspecific hybrids as lineages mixture of aetiological agents that are fungal (for example,micro- come into contact72.Evidence of the effect of multiple fungal co- sporidian (Nosema ceranae)),viral (for example,Kashmir bee virus dispersal events and recombination can also be seen in the recent and Israeli acute paralysis virus)and ectoparasitic (for example,Varroa C.gattii outbreaks in northwestern North America.In this case,strains destructor)in origin.So far,no single environmental cause has been that do not normally recombine have increased their virulence by identified that can account for the apparent reduction in the ability of undergoing recombination and adaptation to overcome mammalian honeybee colonies to resist these infections,and agricultural chemicals, immune responses2367.Recent studies based on the resequencing of malnutrition and modern beekeeping practices have all been suggested as B.dendrobatidis genomes have shown that,although several lineages potential cofactors for colony-collapse disorder.The increasing use of exist,only a single lineage (known as the B.dendrobatidis global azole-based agricultural chemicals has been implicated as a factor under- panzootic lineage)has emerged in at least five continents during the pinning the increase in the frequency of multiple-triazole-resistant twentieth century to cause epizootic amphibian decliness.Notably,the (MTR)isolates of A.fumigatus infecting humans.The widespread agri- genome of the B.dendrobatidis global panzootic lineage shows the cultural use of azoles as a means of combating crop pathogens is specu- hallmarks of a single hybrid origin and,when compared against other lated to have led to selection for MTRalleles,an idea that is supported by the recent discovery that resistance clusters onto a single lineage in Dutch newly discovered lineages of B.dendrobatidis,is more pathogenic, suggesting that transmission and onward spread of the lineage has been populations of the fungus.Efforts must now be turned to integrating epidemiological studies with those on environmental change so that the facilitated by an increase in its virulence.Given that the rate of intra-and many possible interactions and outcomes can be assessed,as making inter-lineage recombination among fungi will be proportional to the blanket predictions for fungal diseases is currently impossible.The contact rates between previously geographically separate populations highly coordinated response to the recent outbreak of wheat stem rust and species,these data from across plant and animal fungal patho- systems suggest that the further evolution of new races is inevitable given (P.graminis,strain Ug99)is a positive step towards this goal current rates of homogenization of previously allopatric,geographically Fungal EIDs impact food security and ecosystem services separated,fungal lineages. Impacts of fungal diseases are clearly manifested in crops and there are Environmental change as a driver of fungal EIDs direct measurable economic consequences associated with die-off in forest and urban environments.Losses that are due to persistent and Climate fluctuation can be a potent cofactor in forcing changing epidemic outbreaks of fungal and oomycete infection in rice(rice blast patterns of fungal phenology?3 and are known to govern plant fungal caused by Magnaporthe oryzae),wheat (rust caused by p.graminis), EIDs.Models of climate change for the coming decades predict increases maize(smut caused by Ustilago maydis),potatoes (late blight caused in global temperature,atmospheric CO2,ozone and changes in humidity, by P.infestans)and soybean(rust caused by Phakospora pachyrizi)vary rainfall and severe weather?.For this reason,many interactions must be regionally but pose a current and growing threat to food security2.Our taken into consideration when attempting to predict the future effects of estimates of loss of food are based on the 2009-10 world harvest stat- climate change on plant diseases?s.First,the physiological and spatial istics of five of our most important crops and make certain basic changes that plants may undergo in response to the various different assumptions of calorific value and worldwide average production components of climate change and the resulting effects on the patho- (Supplementary Table 1).Our calculations show that even low-level gen?,and second,the effects on the pathogen's physiology and dispersal persistent disease leads to losses that,if mitigated,would be sufficient external to their plant hosts'.Frequently,however,experimental models to feed 8.5%of the 7 billion humans alive in 2011.If severe epidemics in have only taken into account one element of climate change,a common all five crops were to occur simultaneously,this would leave food suf- example being the free-air COz enrichment (FACE)studies that model ficient for only 39%of the world's population,but the probability of such the effects ofelevated atmospheric COz(ref.77).A notable result here has an event occurring is very low indeed. been rice blast severity being higher at higher COz levels".However, Invasive tree diseases have caused the loss of approximately 100 million although there has been a general trend for increased disease severity elm trees in the United Kingdom and the United States,and3.5 billion under simulated climate-change conditions",and although some species chestnut trees have succumbed to chestnut blight in the United States are thought to be changing their distribution in response to these changes (Supplementary Table 5).Losses of western Canadian pine trees to the (for example,P.graminis"),other elements of climate change,such as mountain pine beetle-blue-stain fungus association will result in the 12 APRIL 2012 VOL 484 2012 Macmillan Publishers Limited.All rights reservedsuggests that the disease may have been vectored from this region in contaminated soil65. Accelerated evolution of virulence in pathogenic fungi Human activities are not only associated with the dispersal of patho￾genic fungi, they also interact with key fungal characteristics, such as habitat flexibility, environmental persistence and multiple reproductive modes, to cause the emergence of disease. Importantly, many fungi are flexible in their ability to undergo genetic recombination, hybridization or horizontal gene transfer66, causing the clonal emergence of patho￾genic lineages but also allowing the formation of novel genetic diversity leading to the genesis of new pathogens56, 67,. Reproductive barriers in fungi are known to evolve more rapidly between sympatric lineages that are in the nascent stages of divergence than between geographically separated allopatric lineages, in a process known as reinforcement68,69. As a consequence, anthropogenic mixing of previously allopatric fungal lineages that still retain the potential for genetic exchange can drive rapid macroevolutionary change. Although many hybrids are inviable owing to genome incompatibilities, large phenotypic leaps can be achieved by the resulting ‘hopeful monsters’, leading to host jumps and increased virulence70. Such mechanisms are thought to drive the formation of new pathotypes in plant pathogens52, and oomycetes as well as fungi exhibit the genesis of new interspecific hybrids as lineages come into contact71,72. Evidence of the effect of multiple fungal co￾dispersal events and recombination can also be seen in the recent C. gattii outbreaks in northwestern North America. In this case, strains that do not normally recombine have increased their virulence by undergoing recombination and adaptation to overcome mammalian immune responses23,67. Recent studies based on the resequencing of B. dendrobatidis genomes have shown that, although several lineages exist, only a single lineage (known as the B. dendrobatidis global panzootic lineage) has emerged in at least five continents during the twentieth century to cause epizootic amphibian declines64. Notably, the genome of the B. dendrobatidis global panzootic lineage shows the hallmarks of a single hybrid origin and, when compared against other newly discovered lineages of B. dendrobatidis, is more pathogenic, suggesting that transmission and onward spread of the lineage has been facilitated by an increase in its virulence. Given that the rate of intra- and inter-lineage recombination among fungi will be proportional to the contact rates between previously geographically separate populations and species, these data from across plant and animal fungal patho￾systems suggest that the further evolution of new races is inevitable given current rates of homogenization of previously allopatric, geographically separated, fungal lineages. Environmental change as a driver of fungal EIDs Climate fluctuation can be a potent cofactor in forcing changing patterns of fungal phenology73 and are known to govern plant fungal EIDs. Models of climate change for the coming decades predict increases in global temperature, atmospheric CO2, ozone and changes in humidity, rainfall and severe weather74. For this reason, many interactions must be taken into consideration when attempting to predict the future effects of climate change on plant diseases75. First, the physiological and spatial changes that plants may undergo in response to the various different components of climate change and the resulting effects on the patho￾gen76, and second, the effects on the pathogen’s physiology and dispersal external to their plant hosts75. Frequently, however, experimental models have only taken into account one element of climate change, a common example being the free-air CO2 enrichment (FACE) studies that model the effects of elevated atmospheric CO2 (ref. 77). A notable result here has been rice blast severity being higher at higher CO2 levels78. However, although there has been a general trend for increased disease severity under simulated climate-change conditions79, and although some species are thought to be changing their distribution in response to these changes (for example, P. graminis80), other elements of climate change, such as increased ozone, have been shown to have the opposite effect (for example, in Puccinia recondita77). Evidence for the idea that climate change has an impact on the dynamics and distribution of animal-infecting fungi is less clear-cut than that in relation to plant-infecting fungi and, although arguments have been made that warming trends may have contributed to the emergence of B. dendrobatidis in Central America and Europe81,82, there is active debate about these conclusions83,84. Regardless, it is clear that the disease state, chytridiomycosis, is linked to environmental factors; regional climate warming can increase the local range of the pathogen54 and disease risk is inversely related to rates of deforestation85. Correlations between ecosystem change and a rise in infection by opportunistic patho￾gens has been proposed to account for the occurrence of coral reef declines worldwide. For example, disease caused by a variety of microbes threatens hard corals to the extent that two of the most abundant Caribbean reef-builders (staghorn and elkhorn corals) are now listed under the US Endangered Species Act. Across varied reef systems, the occurrence of warm-temperature anomalies leading to bleaching events is associated with increases in disease caused by opportunistic pathogens such as A. sydowii86. In an allied colonial system, colony collapse disorder has resulted in steep declines of the European honeybee Apis mellifera in Europe and North America87. These losses seem to be influenced by a mixture of aetiological agents that are fungal (for example, micro￾sporidian (Nosema ceranae)), viral (for example, Kashmir bee virus and Israeli acute paralysis virus) and ectoparasitic (for example, Varroa destructor) in origin. So far, no single environmental cause has been identified that can account for the apparent reduction in the ability of honeybee colonies to resist these infections, and agricultural chemicals, malnutrition and modern beekeeping practices have all been suggested as potential cofactors for colony-collapse disorder88. The increasing use of azole-based agricultural chemicals has been implicated as a factor under￾pinning the increase in the frequency of multiple-triazole-resistant (MTR) isolates of A. fumigatus infecting humans89. The widespread agri￾cultural use of azoles as a means of combating crop pathogens is specu￾lated to have led to selection for MTR alleles, an idea that is supported by the recent discovery that resistance clusters onto a single lineage in Dutch populations of the fungus90. Efforts must now be turned to integrating epidemiological studies with those on environmental change so that the many possible interactions and outcomes can be assessed, as making blanket predictions for fungal diseases is currently impossible91. The highly coordinated response to the recent outbreak of wheat stem rust (P. graminis, strain Ug99) is a positive step towards this goal77,92. Fungal EIDs impact food security and ecosystem services Impacts of fungal diseases are clearly manifested in crops and there are direct measurable economic consequences associated with die-off in forest and urban environments. Losses that are due to persistent and epidemic outbreaks of fungal and oomycete infection in rice (rice blast caused by Magnaporthe oryzae), wheat (rust caused by P. graminis), maize (smut caused by Ustilago maydis), potatoes (late blight caused by P. infestans) and soybean (rust caused by Phakospora pachyrizi) vary regionally but pose a current and growing threat to food security2 . Our estimates of loss of food are based on the 2009–10 world harvest stat￾istics of five of our most important crops and make certain basic assumptions of calorific value and worldwide average production (Supplementary Table 1). Our calculations show that even low-level persistent disease leads to losses that, if mitigated, would be sufficient to feed 8.5% of the 7 billion humans alive in 2011. If severe epidemics in all five crops were to occur simultaneously, this would leave food suf￾ficient for only 39% of the world’s population, but the probability of such an event occurring is very low indeed. Invasive tree diseases have caused the loss of approximately 100 million elm trees in the United Kingdom and the United States52,93, and 3.5 billion chestnut trees have succumbed to chestnut blight in the United States (Supplementary Table 5). Losses of western Canadian pine trees to the mountain pine beetle–blue-stain fungus association will result in the REVIEW RESEARCH 12 APR IL 2012 | VOL 484 | NATURE | 191 ©2012 Macmillan Publishers Limited. All rights reserved