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The grape powdery mildew fungus, Erysiphe necator, was introduced into Europe more than 160 years ago and is now distributed everywhere that grapes are grown. To understand the invasion history of this pathogen we investigated the evolutionary relationships between introduced populations of Europe, Australia and the western United States (US) and populations in the eastern US, where E. necator is thought to be native. Additionally, we tested the hypothesis that populations of E. necator in the eastern US are structured based on geography and Vitis host species.
We sequenced three nuclear gene regions covering 1803 nucleotides from 146 isolates of E. necator collected from the eastern US, Europe, Australia, and the western US. Phylogeographic analyses show that the two genetic groups in Europe represent two separate introductions and that the genetic groups may be derived from eastern US ancestors. Populations from the western US and Europe share haplotypes, suggesting that the western US population was introduced from Europe. Populations in Australia are derived from European populations. Haplotype richness and nucleotide diversity were significantly greater in the eastern US populations than in the introduced populations. Populations within the eastern US are geographically differentiated; however, no structure was detected with respect to host habitat (i.e., wild or cultivated). Populations from muscadine grapes, V. rotundifolia, are genetically distinct from populations from other Vitis host species, yet no differentiation was detected among populations from other Vitis species.
Multilocus sequencing analysis of the grape powdery mildew fungus is consistent with the hypothesis that populations in Europe, Australia and the western US are derived from two separate introductions and their ancestors were likely from native populations in the eastern US. The invasion history of E. necator follows a pattern consistent with plant-mediated dispersal, however, more exhaustive sampling is required to make more precise conclusions as to origin. E. necator shows no genetic structure across Vitis host species, except with respect to V. rotundifolia.
Introduced pathogens have led to devastating epidemics in naïve host populations that lack evolved defences, as demonstrated by the plant pathogen Cryphonectria parasitica, the fungus that causes chestnut blight. Its introduction from Asia  practically eliminated the American chestnut (Castanea dentata) and markedly altered the species composition of forests throughout eastern North America. Source pathogen populations are expected to be more diverse than introduced populations because introduced populations have smaller effective population sizes due to losses in genetic diversity from population bottlenecks and genetic drift associated with small founder population sizes [2, 3]. However, this pattern could be reversed if multiple divergent lineages from separate sources colonize an area [4, 5]. Where introductions are few, haplotypes in introduced populations should be a subset of those in the source population [6, 7]. Additionally, for sexually reproducing organisms, recombination from sexual reproduction may be more prevalent in source or native populations, whereas clonal reproduction may dominate in introduced or marginal populations since multiple mating types necessary for sexual reproduction may not be present [8–10]. However, lack of variation in introduced populations can make it difficult to detect recombination.
The focus of this research is the invasion history and population structure of the grape powdery mildew fungus, Erysiphe necator (formerly Uncinula necator), an obligate parasite of Vitis species that was introduced into Europe and, eventually, all other wine-producing regions of the world. Historical records support the hypothesis that the source of the introduction is eastern North America . Powdery mildew was described on grapes in North America in 1834, prior to its discovery in Europe in 1845 . Eastern North America is the centre of origin for many wild species of Vitis that have relatively high levels of resistance to many diseases and pests of grapevines, including powdery mildew [13, 14]. After its introduction to Europe, grape powdery mildew was observed throughout all wine-producing regions of the world, including California in 1859  and Australia in 1866 . E. necator most likely dispersed long distances by the movement of grapevines, which were frequently traded between continents in the mid-1800's and later. E. necator remains dormant as mycelium in dormant buds, or as sexual spores in cleistothecia in the bark of vines [17, 18].
Population genetic studies on E. necator to date have been limited to introduced populations in Europe and Australia where two distinct, yet sympatric, genetic groups have been consistently found [19–25]. The groups, designated as A and B (or groups I and III in earlier studies), were originally identified using anonymous markers assayed by RAPDs, ISSRs and AFLPs. Subsequent gene sequence analysis detected fixed nucleotide differences between groups at several nuclear loci, including 14 α-demethylase (CYP51), the internal transcribed spacer (ITS) regions of ribosomal DNA (rDNA) , and beta-tubulin (TUB2) . In India, a third genetic group was found, defined by RAPDs and a unique ITS sequence [19, 26]. Small differences in reproductive fitness  and temporal variation have been found between groups A and B [22, 23, 25, 26] leading to the hypothesis that temporal variation between the groups may be maintaining the differentiation by preventing interbreeding . Group A is genetically less diverse than group B, thus it has been suggested that it is clonal, whereas group B is sexually reproducing [19, 23]. Groups A and B produce viable sexual progeny (ascospores) in laboratory crosses [21, 22, 29], but recombinants have not been found in nature.
We had two major objectives for this study. First, to understand the evolutionary processes that led to the existence of groups A and B of E. necator in introduced populations, we tested the hypothesis that A and B were derived from separate introductions, as opposed to diverging after their introduction. To address this question, it was essential to study the population structure in eastern North America, the putative source population. Because no information was available on the population genetics of E. necator in North America, our major second objective was to describe the diversity and population structure in the eastern Unites States (US). We tested the hypothesis that if the eastern US population was a potential source of introductions, haplotypes found in introduced populations of Europe, Australia, and the western US would also be found in the eastern US. Moreover, we predicted that populations in the eastern US would have greater haplotype and nucleotide diversity than introduced populations. Finally, we tested the hypotheses that the population in the eastern US is structured by geography, Vitis host species, or host habitat (wild or cultivated Vitis).
We obtained 146 isolates of E. necator from diverse wild and cultivated Vitis species collected from the eastern US (northeast, southeast and central) and from cultivated V. vinifera from the western US, Europe, and Australia (Table 1; Additional file 1: Table S1). We also collected isolates of powdery mildew (E. necator var. ampelopsidis ) from Parthenocissus quinquefolia. We sequenced a total of 1803 nucleotides from three nuclear gene regions: the internal transcribed spacer and the intergenic spacer regions of nuclear rDNA (ITS/IGS), beta-tubulin (TUB2), and translation elongation factor 1-α (EF1-α). We were unable to amplify IGS from isolates sampled from P. quinquefolia. However, E. necator var. ampelopsidis from P. quinquefolia is markedly divergent with 94.9%, 93.0%, and 91.7% similarity to the consensus sequence of isolates from Vitis spp. for ITS, TUB2, and EF1-α, respectively. For comparison, the lowest sequence similarity within E. necator from Vitis spp. was 99.8%, 99.5%, and 99.4%. Among isolates of E. necator from Vitis spp. there were 37 segregating sites and 45 multilocus haplotypes (Table 2). EF1-α contained the most segregating sites, followed by TUB2, and ITS/IGS. All of the polymorphisms in EF1-α and TUB2 were found in introns or as synonymous substitutions in coding regions.
Vitis host species, host habitats and geographic regions where Erysiphe necator was collected.
1vinifera hybrids refer to interspecific hybrids derived from crosses between the European wine grape, V. vinifera, and wild American Vitis species other than V. labrusca.
2labrusca hybrids (i.e. 'Concord' and 'Niagara'; sometimes referred to as V. labruscana) refer to V. vinifera x V. labrusca hybrids that are derived primarily from V. labrusca because of repeated backcrossing.
3Sometimes referred to as Muscadinia rotundifolia.
Haplotypes and polymorphic sites among isolates of Erysiphe necator based on partial sequences of three gene regions.
1Numbers refer to the multilocus haplotypes; letters in parentheses refer to the haplotypes for ITS/IGS (the internal transcribed spacer of rDNA/the intergenic spacer of rDNA), TUB2 (beta-tubulin), and EF1-α (translation elongation factor 1-α), respectively. Group A is represented by haplotype 33 and group B is represented by haplotypes 41-45.
2Only segregating sites are listed, which correspond to the following nucleotide positions in the referenced GenBank accessions: ITS (GQ255473; total length 591 nucleotides): 48, 84, 86, 170, 420, 462; IGS (GQ255476; 347 nt): 108, 206, 211, 216, 223; TUB2 (GQ255475; 442 nt): 24, 37, 79, 82, 128, 183, 207, 288, 316, 344, 356, 368; EF1-α (GQ255471; 423 nt): 2, 9, 25, 33, 102, 189, 210, 227, 228, 231, 336, 381, 384, 420.
3regions are: SE = southeast US, C = central US, NE = northeast US, W = western US, EU = Europe, AU = Australia. N = the number of isolates from each region with the designated haplotype.
4hosts are: vin = V. vinifera, hyb = vinifera hybrids, lab = V. labrusca and labrusca hybrids, aes = V. aestivalis, rip = V. riparia, rot = V. rotundifolia. N = the number of isolates from each host with the designated haplotype.
Based on measurements of Tajima's D , ITS/IGS and EF1-α do not deviate from neutral evolution (Table 3). However, TUB2 deviates significantly from neutrality in the eastern US population. Significant negative values for Tajima's D can result from population bottlenecks followed by rapid population expansion or from selective sweeps acting on or near the loci under investigation. Since this effect is not detected across the entire genome, as would be expected with demographic effects, this is suggestive that the deviation from neutrality in TUB2 is from selection.
Haplotype richness, sequence diversity and neutrality estimates for populations of Erysiphe necator.
1The introduced population comprises Europe, Australia and the western US; the eastern US comprises northeast, southeast and central US (Table 1).
2To account for sample size differences in eastern US (N = 103) and introduced populations (N = 43), we used rarefaction analysis  for haplotype richness, θw, and π in the native population. Diversity estimates where the eastern US population is significantly more diverse than the introduced populations (P < 0.05) are in bold.
3Numbers in parentheses are the number of observed haplotypes among the 103 isolates from the eastern US population without correction by rarefaction analysis.
We estimated several population genetic parameters in the eastern US and introduced populations, including haplotype richness (hR), Watterson's theta (θw), and pairwise nucleotide diversity (π). Haplotype richness is significantly greater in the eastern US than in the introduced populations for each locus and the multilocus haplotypes (Table 3), even when adjustments are made for differences in sample size (see Methods). Additionally, there is greater nucleotide polymorphism (θw) in the eastern US population for TUB2, EF1-α and for all three loci combined. There is greater pairwise nucleotide diversity (π) for EF1-α in the eastern US population. However, π is greater in the introduced population for ITS/IGS.
To determine evolutionary relationships among isolates, we constructed networks for the three gene regions and multilocus haplotypes (Figures 1 and 2). Ancestral haplotypes identified based on rooting probability [32, 33] and maximum parsimony using E. necator var. ampelopsidis as an outgroup were from the eastern US in all cases. Based on maximum parsimony the outgroup haplotypes would be at least 23 mutational steps from the putative ancestors for ITS/IGS, 29 steps for TUB2, 35 steps for EF1-α, and at least 87 steps for the combined multilocus haplotype. Because of this degree of divergence TCS did not place the outgroup in the same network. The internal position of haplotypes from eastern North America is particularly noticeable for the multilocus network (Figure 2), whereas all haplotypes of isolates from introduced populations (represented by striped and stippled patterns) are at or near the tips of the network. Isolates from the western US have the same haplotypes (nos. 41 and 43) as isolates in group B from Europe (Table 2; Figures 1 and 2), which suggests that populations in the western US were introduced from Europe. In addition to the 13 isolates from the western US reported here, 17 isolates from California and one from Oregon had the same IGS sequence that is found only in group B (data not shown). We did not sequence additional loci for these isolates from the western US because all were like group B for IGS.
Haplotype networks of ITS/IGS, TUB2 and EF1-α. Networks constructed in TCS 1.21 [60, 61]. Each haplotype is represented as a circle proportional in size to the number of isolates in each haplotype. Inferred intermediate haplotypes are represented by a small solid dot. Each line segment represents a single mutation. The letters defining haplotypes in Table 2 are shown to the right of each node. Geographic origins of isolates in each haplotype are proportionally represented in pie charts by different patterns shown in the key in the centre of the figure. The ancestral haplotypes determined by root probability  are indicated by asterisks (*), whereas those determined by maximum parsimony using E. necatorvar. ampelopsidisas the outgroup are indicated by §.
Multilocus haplotype network for Erysiphe necator. Network constructed in TCS 1.21 [60, 61]. Each haplotype is represented as a circle proportional in size to the number of isolates in each haplotype. Inferred intermediate haplotypes are represented by a small solid dot. Each line segment represents a single mutation. The numbers defining multilocus haplotypes in Table 2 are shown to the right of each node. Geographic origins of isolates in each haplotype are proportionally represented in pie charts by different patterns shown in the key in the upper left. The haplotypes that include group B isolates are enclosed in a magenta ellipse and marked with a 'B'; the haplotype that includes group A isolates is enclosed in a green ellipse and marked with an 'A'; and the haplotypes that include isolates from muscadine grapes (V. rotundifolia) are enclosed in a blue ellipse and are marked with an 'M'. The ancestral haplotype determined by root probability  is indicated by an asterisk (*), whereas that determined by maximum parsimony using E. necatorvar. ampelopsidisas an outgroup is indicated by §.
The majority of haplotypes for the individual loci, and especially for the multilocus network, are represented by individuals from the eastern US populations, demonstrating that populations in the eastern US are more diverse than in Europe, Australia and the western US. The sample size from the eastern US population is larger; however, this difference is accounted for in the comparisons of diversity estimates by rarefaction analyses. Although isolates from the central US are represented by diverse haplotypes, they are mostly derived haplotypes at or near the tips of the multilocus network, which suggests that this region is peripheral to the centre of diversity. All isolates obtained from V. rotundifolia belonged to two multilocus haplotypes (nos. 34 and 35; labelled 'M' in Figure 2) at the tips, derived from group A (haplotype no. 33) and not shared by isolates from any other host species.
The haplotype networks show that genetic groups A and B from introduced populations are distinct from each other at all loci and are derived from North American ancestors (Figures 1 and 2). Because of these differences, and the internal position of North American haplotypes, groups A and B almost certainly represent two separate introductions instead of diverging after introduction. We found no genetic variation among group A isolates, and this same multilocus haplotype (no. 33) was common in the southeastern US in isolates from diverse wild and cultivated host species, including V. vinifera, vinifera hybrids, V. aestivalis, and V. riparia (Additional file 1: Table S1; Table 2). In contrast, we found five multilocus haplotypes (nos. 41-45) forming a discrete lineage in group B; none of these multilocus haplotypes was found in eastern North America. However, group B does not differ from the eastern US population at all loci (Figure 1; Table 2). It differs for ITS/IGS, yet shares several haplotypes for EF1-α and TUB2 with the eastern US population.
Differentiation was estimated between the eastern US and introduced populations, and among geographic regions, Vitis host habitats, and Vitis host species in eastern US. Eastern US and introduced populations are significantly differentiated (Table 4). Within the eastern US, we detected significant differentiation among geographic regions (southeast US, northeast US, and central US). Geographic differentiation within the eastern US was detected when isolates from all hosts were included in the analysis. Because many hosts are more abundant in particular geographic regions (for example, V. riparia in the northeast US or V. rotundifolia in the southeast US), we conducted tests of geographic subdivision on isolates collected only from V. vinifera and vinifera hybrid hosts, which are found abundantly among the three regions, to avoid confounding host and geography. Geographic subdivision was still evident when the analyses only included isolates from V. vinifera and vinifera hybrid hosts (Table 4).
Population structure of Erysiphe necator by geographic region and host species.
1The nearest neighbour statistic (Snn) measures the proportion of times the most similar sequence ('nearest neighbour') is from the same population . HST is a measure of population subdivision that estimates FST among haplotypes . Significant differentiation between or among populations (α = 0.05) is shown in bold. P-values are in parentheses.
2Isolates from the central US were excluded because all but one were from cultivated species.
3A single isolate from V. riparia was excluded from the southeast population.
There was no differentiation between populations from wild and cultivated host habitats or among host species within geographic regions (Table 4), except when isolates from V. rotundifolia were included in the analyses.
The multilocus haplotype network (Figure 2) demonstrates that the eastern US population is ancestral to the introduced populations [32, 33]. Therefore, our results are consistent with the hypothesis that E. necator was introduced into Europe from eastern North America  because populations in Italy and France are derived from North American ancestors. Additionally, populations in California share haplotypes with populations from Europe, suggesting the possibility that they could have been introduced from Europe; the reverse direction of introduction is less likely given the historical records of trade in grapevines and that grape powdery mildew was first observed in Europe in 1845, but not in California until 1859. However, we cannot make any firm conclusions because we do not know which genetic group, A or B, was introduced into Europe first. Populations in the eastern US are more genotypically diverse than those in Europe, Australia and the western US. Several of the haplotypes for individual loci in the introduced populations were found in eastern North America, which is expected when comparing source and introduced populations. An alternative hypothesis, that E. necator was introduced into Europe from Japan has been suggested , but there is no evidence to support this claim and we were unable to obtain samples from Japan for this study.
At least two haplotypes of the grape powdery mildew fungus, progenitors of groups A and B, were introduced and successfully invaded Europe and Australia. If there had been a single introduction, individuals in the introduced populations would represent a monophyletic group; the single introduction hypothesis can be rejected based on the relationships of group A and B haplotypes in the multilocus network (Figure 2). The introductions, and successful invasions, may have occurred at separate times or multiple, distinct haplotypes may have been introduced during a single event. Previous studies in French and Australian populations of E. necator, based on anonymous markers, also found greater diversity in group B than in group A [21, 23] and it has been hypothesized that group A is predominantly asexual, while group B undergoes sexual recombination. Most studies have shown that group A is dominated by a single mating type [19, 21, 23]. We expected to find both genetic groups from the introduced populations in the eastern US population. However, we found isolates in the southeastern US with the same multilocus haplotype as that in group A, but we did not find any with the same haplotype as those in group B. Group B haplotypes may have diverged by genetic drift from the original founders since the first introductions into Europe more than 160 years ago. Sexual reproduction and recombination in group B, coupled with selection for new haplotypes on a different host species and in environmental conditions in Europe, could also have led to divergence. Alternatively, our sample size in eastern North America may not have been large enough to include haplotypes that are less common in the eastern US population, which by chance could have been introduced into Europe. An alternative explanation is that the unique alleles specific to genetic group B came from an entirely different source, which we did not sample for this study.
Genotypic diversity was significantly greater in the eastern US population than in introduced populations, although measures of gene diversity were not always greater (Table 3). In fact, pairwise nucleotide diversity (π) was significantly greater for ITS/IGS in the introduced population. One explanation for this finding is that the occurrence of two distinct genetic groups in the introduced populations results in high gene diversity because of fixed nucleotide differences between lineages, but low genotypic diversity because there is little or no variation within groups. This discrepancy is similar to finding high gene diversity combined with low genotypic diversity in clonal diploid populations with fixed heterozygosity [35, 36]. Multiple introductions of distinct lineages from different sources into new ranges can result in greater diversity than expected during an invasion [4, 5]. Additionally, gene diversity was overestimated in Europe and Australia because our samples were not random, but rather were artificially constructed with roughly equal numbers of isolates from the two genetic groups, whereas group B is typically found at a greater frequency than group A in populations in Europe [19, 22–25]. Moreover, the lack of diversity within groups A and B validated our strategy of sequencing relatively small samples from Europe and Australia where extensive sampling only found these two discrete groups [19–25]. Haplotypic (or allelic) richness is one of the best measures for reductions in diversity associated with population bottlenecks because rare haplotypes are often lost during founder events even if overall gene diversity is not largely affected .
Our results are consistent with historical records of the movement of grapevines and plant-mediated introductions of E. necator into Europe, California, and Australia. After grape powdery mildew spread throughout Europe by the mid-1850 s, additional vines were imported from eastern North America as sources of resistance. Unfortunately, this resulted in the introduction of additional grape pests and diseases into Europe, including the phylloxera aphid and downy mildew [37, 38]. Additional importations of grapevines from eastern North America for resistance to these pests/diseases may have led also to additional introductions of E. necator. Secondary introductions of E. necator from Europe into California and Australia are also consistent with historical records of the movement of grapevines. During the 1850's and 1860's large collections of V. vinifera were brought to California from Europe . Powdery mildew was first described in California in 1859 and in Australia in 1866 [15, 16], so it is likely that it was introduced on vines imported at this time. Two of the four group B multilocus haplotypes found in Europe are also found in the western US. It is not clear why both genetic groups were introduced into Australia, but only group B is present in California. It is possible that group A is present in California, but at such a low frequency that we did not sample it. Nevertheless, it is surprising that since its introduction over 150 years ago, additional genotypes of E. necator have not been successfully introduced by the movement of vines from the eastern US to Europe, Australia or the western US.
With the exception of specialization on muscadine grapes, V. rotundifolia, we found no genetic differentiation among populations from Vitis host species. This was not unexpected. The best-studied powdery mildew fungus, Blumeria graminis, shows specialization among host genera rather than among species within a genus [40, 41]. Similarly, E. necator demonstrates host specialization at the level of host genus. Gadoury and Pearson  showed that E. necator var. ampelopsidis sampled from P. quinquefolia was only rarely pathogenic on Vitis species, and then only with low virulence. Multilocus sequencing of E. necator var. ampelopsidis, as in the formae speciales of B. graminis, showed that this type of marked host specialization correlates to marked genetic divergence from E. necator on Vitis. Alternatively, there may be population divergence of E. necator among Vitis hosts, but we are not able to detect it with the conserved genes used in this study. Other fungi show specialization at the level of host species. For example, microsatellite markers, which are more polymorphic than multilocus sequences, allowing for better detection of differentiation, showed specialization of Microbotryum violaceum at the level of host species . The lack of specialization could be also explained by recent colonization of Vitis hosts by E. necator or recent diversification of Vitis species in North America. In closely related species or populations undergoing speciation, genetic divergence may only be evident at one or a few loci involved in adaptation and reproductive isolation .
We found that E. necator populations from muscadines are genetically distinct from populations on other Vitis species. Although, the haplotypes of muscadine isolates differ from those from other Vitis species by one or two mutations there is a strong phenotypic difference that is a potential isolating mechanism. Another study demonstrated marked host specialization to muscadine in laboratory inoculations, but not among other Vitis species . Although isolates from muscadines could infect other Vitis species in the lab, we did not find haplotypes from the muscadine lineage from other Vitis species in the field even when they were sympatric with muscadines. Populations of E. necator from muscadine and other Vitis species could be in the early stages of speciation resulting from host specialization. Alternatively, muscadine isolates may have alleles that evade recognition by host defences in a gene-for-gene interaction. Resistance to powdery mildew controlled by a single, but complex, genetic locus has been demonstrated in muscadines, which is a source of resistance in breeding programs . It is important to test any new resistant cultivars derived from muscadines with diverse powdery mildew populations from the regions where muscadines are endemic to ensure that the resistance would be durable.
Population differentiation of E. necator was not detected between wild and cultivated hosts. In some cases, crop domestication can lead to the divergence of pathogen populations on wild relatives and crop plants . Moreover, management strategies or high-density cultivation of crop plants can lead to population differentiation between pathogens from natural ecosystems and agricultural ecosystems . The lack of population structure in E. necator indicates that gene flow is presently occurring or has occurred historically between the powdery mildew populations from wild and cultivated hosts.
Our results are consistent with the hypotheses that populations of the grape powdery mildew fungus, E. necator, in Europe are derived from two separate introductions and that their ancestors were likely from native populations in the eastern US. Multilocus sequencing analysis and historical records are also consistent with the hypothesis that the initial introductions into Europe were followed by secondary introductions from Europe into the western US and Australia and were likely the result of plant-mediated dispersal in the grapevines that were frequently traded between continents during the time of introductions. Within the eastern US, populations of E. necator do not demonstrate divergence based on host habitat or Vitis host species, with the exception of specialization to muscadine grapes, V. rotundifolia.
Powdery mildew fungi are haploid ascomycetes that are obligate parasites of plants that produce colonies of superficial hyphae and asexual spores (conidia). E. necator infects Vitis species and other members of the Vitaceae. E. necator can also reproduce sexually if individuals of both of the two mating types are present .
Diverse wild Vitis species are found throughout eastern North America , with many of the species demonstrating at least some susceptibility to powdery mildew . We sampled E. necator from cultivated grapes and from four of the most common wild species: V. riparia, V. aestivalis, V. labrusca, and V. rotundifolia (Table 1). V. riparia is common in colder regions of central and northeastern North America. Both V. aestivalis and V. labrusca are distributed throughout the northeastern US and the higher elevations in the southeastern US. The muscadine grape, V. rotundifolia, which is endemic to and widely distributed throughout the southeastern US, has considerable resistance to powdery mildew , and is genetically and morphologically distinct from other Vitis spp., such that it is sometimes considered to be in a separate genus, Muscadinia .
Cultivated varieties grown throughout eastern North America are also diverse. Interspecific hybrids derived from crosses between the European wine grape, V. vinifera, and wild American Vitis species are common as cultivated vines . Cultivated labrusca hybrids (i.e. 'Concord' and 'Niagara'; sometimes referred to as V. labruscana) were derived mostly from backcrossing to V. labrusca and are grown in colder climates of eastern North America. In contrast to the diversity of hosts in eastern North America, most other major wine-producing regions are dominated by V. vinifera, which is native to Eurasia  and highly susceptible to E. necator .
We sampled E. necator from the eastern US (northeast, southeast, central) and western US (Additional file 1: Table S1). Most of our sampling from wild host species in the southeast was limited to higher elevations because we were not able to find mildew on wild species other than V. rotundifolia at lower elevations of the coastal plain. We speculate that this was due to high temperatures and drought that were not conducive to mildew for several weeks prior to our sampling in 2008. Samples from the eastern US were collected to maximize the diversity of host species and host habitats. Samples from France, Italy and Australia were obtained from collaborators who generously sent genomic DNA from E. necator isolates collected from cultivated V. vinifera and previously identified as genetic group A or B (Additional file 1: Table S1). In this respect, samples from France, Italy and Australia do not represent random samples but they do reflect the diversity found in each country. Populations of E. necator in Europe and Australia have been extensively sampled across broad geographic regions [19–24]. Among these studies, a total of approximately 1000 E. necator isolates were genotyped with various markers, and each study demonstrated that populations are structured into two genetic lineages designated as groups A and B. We reasoned that additional sampling was not necessary in Europe and Australia for this study because little genetic diversity had been found within the two lineages despite extensive sampling from different cultivars, years, and times of year. We consider that our sampling represents the diversity of isolates in Europe and Australia since the isolates came from both genetic groups across different regions of France, Italy and Australia (we were not able to obtain DNA from other locations with published reports of previous genotyping). In fact, the isolates we sequenced from Australia were identified as having distinct genotypes , representative of the total genetic diversity found there previously. Cultivated V. vinifera is the only host plant E. necator was sampled from in Europe and Australia because this is the dominant species present in these regions. Therefore, we did not sample from wild species outside of the eastern US.
Isolates of powdery mildew from Parthenocissus quinquefolia, also in the Vitaceae, were collected in Ithaca, NY, USA for comparison with powdery mildew from Vitis species. Powdery mildew from P. quinquefolia is considered variety ampelopsidis of E. necator . Isolates from Parthenocissus species exhibit host specialization, although some can infect V. vinifera but with greatly reduced growth compared to isolates from V. vinifera .
Mildew isolates were maintained as described by Evans et al.  on young leaves of V. vinifera 'Cabernet Sauvignon' grown in a greenhouse. Leaves were surface-sterilized in 0.6% sodium hypochlorite for 1.5 min, rinsed twice with sterile distilled water and air dried in a sterile laminar flow hood. Leaves were kept in Petri dishes containing 20 ml of 2% water agar. Colonies of E. necator were initially isolated by touching a mildew colony from an infected leaf to a surface-sterilized leaf. Asexual spores (conidia) from the resulting colonies were transferred 6-12 days later with a sterile pipette tip to another surface-sterilized leaf at least once to rid the colonies of contaminants prior to DNA extraction. Isolates were maintained by transferring to new leaves approximately once per month.
For DNA extraction, conidia and hyphae were collected from colonies 2-3 weeks after inoculation by touching a 1-cm2 piece of office tape (Scotch Tape, 3M) to the colony multiple times until the tape was covered in fungal tissue. The tape was placed in a 1.5 mL microcentrifuge tube with 100 μL of 5% chelex [57, 58], vortexed for 30 sec and incubated at 95 °C for 20 min. The solution was vortexed again for 5 sec centrifuged briefly, and the supernatant was removed and used as the DNA template for PCR.
Three nuclear loci were PCR-amplified and sequenced from each isolate. The gene regions we sequenced included: ITS/IGS, TUB2, and EF1-α. ITS  and TUB2  had been identified previously in E. necator, whereas IGS and EF1-α were identified in E. necator in this study. For ITS, we developed primers ITSEnF: 5′-AAGGATCATTACAGAGCGAGAGG-3′ and ITSEnR: 5′-GGATGACCGGACAAAGGTG-3′. For TUB2, we designed primers Bt2c: 5′-CAGACTGGCCAATGCGTA-3′ and Bt2d: 5′-AGTTCAGCACCCTCGGTGTA-3′ based on the published sequence (GenBank accession no. AY074934) . We identified the IGS region in E. necator with the conserved ascomycete primers IGS-12a and NS1R , then developed primer IGSEn1: 5′-TTTCGGGGGAAAGCCACCA-3′ to pair with NS1R for improved PCR amplification. EF1-α was identified in E. necator by designing degenerate primers to conserved regions of EF1-α in Sclerotinia sclerotiorum (GenBank accession no. DQ471086) and Botrytis cinerea (GenBank accession no. DQ471045). We then developed primers EF1-5: 5′-ATAGCGACGATGAGCTGCTT-3′ and EF1-6: 5′-TCGAAAAGGTTTGTTGCAGA-3′ for improved PCR amplification. The PCR reactions for ITS, IGS, and TUB2 were carried out in a total volume of 25 μL. Reaction components included 2.5 μL of 10 × PCR buffer (Takara Bio, Inc.), 2.5 μL dNTPs, 1.25 μL of 10 μM forward and reverse primers, 0.75 U ExTaq (Takara Bio, Inc.), and 1 μL DNA template. Cycling conditions included an initial denaturation at 95°C for 2 min followed by 35 cycles with a denaturation step at 94.5°C for 1 min, annealing at 56°C for 1 min, extension at 72°C for 1 min, followed by a final extension at 72°C for 5 min. PCR products were purified with QIAquick spin columns (QIAGEN). The PCR reaction for EF1-α was carried out in a total volume of 50 μL with all components added at 2 × the volumes used in the reactions for the other loci. Thermal cycling was carried out as described for the other loci. The EF1-α PCR products were purified by electrophoresis in a 1% agarose gel, excision of the band and purification with the QIAEX II Gel Extraction Kit (QIAGEN). All DNA fragments were sequenced at the Cornell University Life Sciences Core Laboratories Centre using the Applied Biosystems Automated 3730 DNA Analyzer with Big Dye Terminator chemistry and AmpliTaq-FS DNA Polymerase. All gene regions were sequenced in both directions in at least one isolate. Sequences of EF1-α, ITS, TUB2 and IGS for haplotype 1 (Table 2) are deposited in GenBank with accession numbers GQ255471, GQ255473, GQ255475, and GQ255476, respectively. Sequences of EF1-α, ITS and TUB2 and from E. necator var. ampelopsidis isolates from P. quinquefolia are deposited under accession numbers GQ255474, GQ255470 and GQ255472, respectively.
Sequences were aligned and manually edited in SeqMan (DNASTAR, Inc). Haplotype networks were constructed for each locus and for combined multilocus sequences by statistical parsimony with the program TCS 1.21 [60, 61]. Haplotype networks are preferable for intraspecific analyses because they allow for the coexistence of ancestral and derived haplotypes and account for recombination . Alternative, most parsimonious networks are accounted for by this method as loops in the network. The networks were assembled based on an absolute distance matrix between haplotypes, i.e., the number of mutations separating each haplotype, with a parsimony probability of 95%. The ancestral haplotype for each network was predicted based on rooting probability, which assesses the frequency of a particular haplotype and the number of linkages . We also predicted the ancestral haplotype by maximum parsimony using E. necator var. ampelopsidis as an outgroup. Outgroup haplotypes could not be incorporated into the network with TCS due to high divergence.
To compare diversity between source and introduced populations we estimated several population genetic parameters. They include: haplotype richness (hR), the total number of haplotypes; Watterson's theta (θw), which is a measure of nucleotide polymorphism equivalent to 2Neμ (in a haploid population) and an estimate of the effective population size ; and π, the pairwise nucleotide diversity . Each parameter was estimated for the eastern US and introduced populations separately using DnaSP v5 . To avoid the bias in diversity estimates caused by differences in sample sizes, we used bootstrapping to conduct rarefaction analysis . For the eastern US population, we sampled a smaller numbers of individuals, with replacement, equal to the sample size of the introduced population and estimated hR, θw, and π. This was repeated 1000 times and the median estimates for each parameter were recorded. We conducted a one-tailed test to determine if eastern US populations were more diverse than introduced populations. P-values were estimated as the proportion of the null distribution that was less than the observed diversity estimate for the introduced population.
Tajima's D  was calculated by using DnaSP v5 to test for departure from an equilibrium neutral model of evolution. Significant departures from neutrality were determined by permutation tests with 1000 replications.
Differentiation among geographic regions, host habitats, and host species in eastern North America was estimated on combined multilocus sequences. For these analyses labrusca hybrids were grouped with V. labrusca rather than the vinifera hybrid group since they are most similar to V. labrusca (National Grape Registry http://ngr.ucdavis.edu. The nearest neighbour statistic (Snn) measures how often the most similar sequence or sequences ('nearest neighbour') is from the same designated population . This statistic was selected for analyses because it has high power with small sample sizes. Snn estimates the proportion of nearest neighbours that are from the same population versus from a different population. With two populations, for example, a value close to 1 suggests that the two populations are highly differentiated, because almost every sequence would be most similar to other sequences from the same population, whereas a value of 0.5 would be expected if populations are not genetically structured because the closest sequences would be most similar to those from either population with equal probability. We also estimated differentiation with HST, a powerful measure of population subdivision that estimates FST among haplotypes . Both Snn and HST were calculated by using DnaSP v5. P-values were estimated by permutation tests with 1000 replications.
We thank all of the generous collaborators who helped us collect E. necator by assisting in our sampling at field sites, by collecting powdery mildew samples or by sending us DNA. We especially thank Sam Anas, Omer Frenkel, W. Douglas Gubler and Turner Sutton for helping us locate and collect samples in the field; and Marie-France Corio-Costet, Paolo Cortesi, Franco Faretra, Monica Miazzi, Jean-Pierre Péros, Eileen Scott and Brenda Stummer for sending DNA. We also thank Paolo Cortesi, Lance Cadle-Davidson, Omer Frenkel, Rick Harrison and anonymous reviewers for helpful comments on earlier drafts of this manuscript. This research was funded, in part, by grants from Hatch projects NYC-145854 and NYC-153410, and a Research Travel Grant from the Cornell University Graduate School to MTB.
MTB participated in the design of the study, conducted the research, analyzed the data, interpreted the results, and wrote the manuscript. MGM conceived the study, participated in the design of the study, performed some of the analyses, assisted with interpreting the results, and critically revised drafts of the manuscript. Both authors read and approved the final manuscript.

matches: V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V. V.


Late last Friday afternoon, President Obama released a long-awaited draft of the Consumer Privacy Bill of Rights Act. Industry and advocates have been waiting for this language since the White House announced support for comprehensive commercial privacy legislation in its February 2012 privacy report. The United States is one of only two developed nations without privacy protections for all personal data (Turkey is the other one); instead, we have a handful of sector-specific laws that apply to narrow categories of personal information, and general purpose consumer protection law enforced by the FTC that maps imperfectly to privacy rights.
CDT is committed to working with the administration and Congress on strengthening this bill to ultimately deliver the privacy rights and protections that we deserve.
We’re glad to see the administration continue to provide needed leadership on this issue. Consumers feel uneasy about how information about them is collected and used, and with the advent of increasingly sophisticated technologies, there is a pervasive sense that we’ve lost control of our privacy. So the administration’s concrete legislative proposal is an incredibly important step. The bill does have some significant flaws, but the administration seems to admit as much by explicitly labeling the Consumer Privacy Bill of Rights a “discussion draft.” A number of elements need to be improved if this bill is going to offer consumers comprehensive protection. As it is, there are too many loopholes, and enforcement is noticeably lacking. CDT is committed to working with the administration and Congress on strengthening this bill to ultimately deliver the privacy rights and protections that we deserve.
As a first step in that process, we’ve put together our initial summary of some of the bill’s most important provisions, along with tentative suggestions for changes. Like the administration, we recognize that our analysis may not take everything into account, so we intend to iterate on this guidance over time. With that caveat, let’s dive right in.
Some have argued in recent years that privacy protection should focus almost exclusively on responsible use at the expense of the other traditional protections; indeed, the President’s Council of Advisors on Science and Technology argued as much this summer in its report on Big Data (the White House’s own Big Data report was more measured). We’re pleased to see that the legislation includes a full range of protections beyond use limitations: minimizing the role of individual control, transparency, and collection limitations is inconsistent with consumer desires and expectations, and unreasonably presumes that nothing bad can happen to stored data. As we have seen in recent years, data security can be compromised, and governments can access commercial data sets often without reasonable due process requirements. Moreover, companies and individuals might not always see eye-to-eye on what constitutes reasonable use. The FTC recently rejected the notion that use limitations are sufficient to safeguard privacy; we’re glad to see the administration do the same.
However, most of the bill’s protections are predicated on a risk of harm. One very important element of the bill is that many of the FIPPs-based protections described above only apply in proportion to the “privacy risk” the data poses (the word “risk” appears 27 times in the 24 page bill). The bill defines “privacy risk” fairly narrowly — it is the potential that data could “cause emotional distress, or physical, financial, professional or other harm to an individual.” §4(g). This is a significant shift away from a rights-based formulation adopted in other privacy legislation. While an assessment of risk makes sense for some protections — such as what level of security or internal accountability to mandate — predicating rights such as individual control (§102) and access-and-correction (§106) on an evaluation of risk is questionable. Predicating rights on this narrow formulation would leave many if not most data sets — such as information collected for marketing purposes — unaddressed. Consumers might reasonably want to limit what gets collected about them — or even know what’s been collected — absent a significant risk of harm or emotional distress. Given that one significant rationale for this legislation is to demonstrate internationally — particularly to Europe — that the United States is serious about reforming its data protection regime, conditioning so much of the bill’s protections on a narrow assessment of harm is counterproductive (the EU’s Article 29 Working Party previously rejected the notion of conditioning rights on an assessment of privacy risk).
The bill also exempts a number of business records from many substantive protections. Similar to personal data that doesn’t pose a risk of privacy harm, many business records are also exempted from protections such as individual control (§102(d)) and data minimization (§104(c)(1)). Certainly, many data records should be exempt from individual control — you can’t opt out of a company’s security database that identifies you as a previous shoplifter. However, the categories of exceptions are extremely broad in this bill (including a tautological definition of “customary business records” in §4(j)), and information collected doesn’t need to be necessary for these purposes, only related. At the very least, reasonable minimization requirements — so that covered entities only collect the data that is needed (instead of simply related) for these purposes — would be an improvement.
The bill applies to companies and non-profits alike. Today, the Federal Trade Commission only has the authority to bring cases against for-profit commercial enterprises. This bill — in addition to expanding the substance of privacy requirements — would also expand the range of institutions to which these requirements apply to non-profit entities as well (meaning CDT would be subject to broad privacy requirements for the first time). §4(b). This is a sensible change, as non-profits — including political campaigns — have the capacity to collect a great deal of potentially sensitive personal information. However, the bill does have an exception for entities that collect information about less than 10,000 people in a year or that have five or fewer employees. §4(b)(1)(D). Given that small developers have the capacity to collect vast amounts of personal information, we’re not entirely convinced that this exception is justified.
The bill has a very broad definition of personal information. The bill applies generally to a wide range of information — considerably beyond the traditional definition of “personally identifiable information” (PII) addressed in some existing sectoral legislation. §4(a). As privacy commentators have recognized for years now, consumers have an interest in pseudonymous identifiers such as device IDs and cookies because (1) those identifiers can be used to dramatically alter individual experiences and (2) information attributed to unique identifiers could — quite easily in many cases — be tied to real world identity. Identifiers for devices that aren’t associated with a particular individual or family — say, a streetlight that is connected to the internet in order to be remotely turned on and off — are reasonably excluded from the definition of personal information.
Out-of-context data collection requires opt-in consent — or approval by a Privacy Review Board. So here’s where the bill gets rather complicated. As noted above, consumers get certain rights if there’s a “privacy risk” posed by that data. However, if data collection is “out of context,” then consumers must be given “Heightened Transparency and Control” over that data (basically, they must provide affirmative consent in response to a clear and prominent prompt). §103(b)(1). When data processing is “unreasonable in light of context” is somewhat hard to parse — there’s an eleven-factor test for what constitutes “context” in the definitions, including consideration of the nature of the institution’s relationship with the consumer and the types of data collected. §4(k). Previous privacy bills such as Representative Rush’s BEST PRACTICES Act and the Kerry-McCain Commercial Privacy Bill of Rights have adopted a simpler approach: opt-out controls for most data, opt-in controls for “sensitive” data. That approach is at the very least more predictable and certainly easier to implement. Alternatively, an obligation to provide just-in-time notice and opt-in controls could be tied to reasonable expectations or the likelihood that a consumer would be surprised by certain practices — arguably, the FTC has used this as a benchmark in previous enforcement actions. One of the key exercises going forward will be to evaluate this creative new idea of context and compare its strengthens and weaknesses against existing approaches.
Notably, the bill does provide for an exception to the requirement for Heightened Transparency and Control if an FTC-approved “Privacy Review Board” (think of a medical research institution’s Institutional Review Board) finds that opt-in control is impractical, and the privacy risks have been minimized and are outweighed by “substantial benefits” that don’t just accrue to the covered entity (this idea is tied to an expectation that big data will have a value to consumers and society). Even if a PRB waived a requirement of consent, the company would still have to provide transparency and individual control under §§101 and 102 of the bill, though general data minimization requirements are curiously overridden (§104(c)(3)). Moreover, whether out-of-context data processing is approved by an individual or a PRB, a disparate impact analysis must be conducted to ensure that the data processing wouldn’t result in unintended discrimination against various protected classes. §103(d). We are wary about transferring too much individual autonomy to obscure and unproven PRBs, but we appreciate the effort to provide a creative solution to the problem of how to encourage societally beneficial secondary though unanticipated uses of data. The idea merits greater exploration.
Retroactive revisions to privacy policies no longer need permission. Under existing law, the Federal Trade Commission has brought enforcement actions against companies who tried to retroactively revise privacy policies to change the rules for previously collected data (that is, a company made certain material representations in its policy at the time of collection, and then retroactively changed the policy to remove those conditions). This of course makes sense — you can’t promise someone at the time of data collection that you won’t sell their email address to a data broker, and then change your mind after the fact. Surprisingly, the President’s bill reverses course on this principle. Under §102(e), companies that change their policies simply need to post information about the change in advance, and then offer “compensating controls designed to mitigate privacy risks” from the change. This weakening of existing law is a bad idea, and this provision should be removed.
The bill has weak enforcement provisions. In order to effectively deter privacy violations, a privacy law needs to have robust enforcement — anemic enforcement powers has been blamed by many for uneven compliance with the Data Protection Directive in Europe. However, the Consumer Privacy Bill of Rights Act is hamstrung by strangely weak enforcement powers. Most notably, privacy fines are calculated not by the number of affected individuals, but by the number of days during which a violation occurs. Thus, if a multibillion dollar company decided to sell millions of records in one day in violation of its promises, under this bill it would face a maximum fine of $35,000 — an incredibly perverse result. State Attorneys General and citizens themselves are not empowered to obtain penalties at all. And new companies get a free pass from penalties for the first 18 months of their existence (consider that Instagram had over a million users within two months of launch — and 150 million pictures and 10 million users in less than a year). If this bill is to be effective in deterring bad privacy practices, the consequences for behaving illegally need to be significant.
The FTC can approve specific Codes of Conduct as “safe harbors.” Given the vagueness surrounding many of the bill’s provisions (including how both risk and context are evaluated), covered entities will be eager for some sort of certainty that a specific set of practices will comply with the law. While the draft bill does not allow for FTC rulemaking to provide more in-depth guidance, it does allow the FTC to bless certain industry-specific codes as compliant with the law. These codes can be developed through the existing National Telecommunications & Information Administration’s (NTIA) multistakeholder process that has delivered mixed results (at best) so far at generating consensus codes of conduct (though presumably institutions will be more incentivized to generate enforceable codes if there are substantive obligations from which you want to establish a safe harbor). Codes can also be developed outside of the NTIA process, potentially entirely by covered entities without multistakeholder input; however, these codes do not enjoy the presumption of validity and streamlined approval process that NTIA codes get. CDT believes that FTC-approved codes can play a helpful role in translating high level legal obligations into industry-specific practices — however, the FTC needs to be given the necessary resources to evaluate the potential influx of proposed codes.
CDT could support broad preemption provisions in a federal bill to create a common national standard, but the underlying substantive standard would need to be quite strong. Unfortunately, the President’s bill is not there at this point — too much personal information is exempted from too many protections, and the enforcement mechanisms won’t be an effective deterrent.
We are committed to working toward a common, strong privacy standard that would apply to all of our personal information. The President and FTC calling for comprehensive privacy legislation were important steps toward that goal. And this draft bill is an important step along the way.


BOOTH v. CHURNER ET AL.
The Prison Litigation Reform Act of 1995 amended 42 U. S. C. § 1997e(a), which now requires a prisoner to exhaust "such administrative remedies as are available" before suing over prison conditions. Petitioner Booth was a Pennsylvania state prison inmate when he began this 42 U. S. C. § 1983 action in Federal District Court, claiming that respondent corrections officers violated his Eighth Amendment right to be free from cruel and unusual punishment by assaulting him, using excessive force against him, and denying him medical attention to treat ensuing injuries. He sought various forms of injunctive relief and money damages. At the time, Pennsylvania provided an administrative grievance and appeals system, which addressed Booth's complaints but had no provision for recovery of money damages. Before resorting to federal court, Booth filed an administrative grievance, but did not seek administrative review after the prison authority denied relief. Booth's failure to appeal administratively led the District Court to dismiss the complaint without prejudice for failure to exhaust administrative remedies under § 1997e(a). The Third Circuit affirmed, rejecting Booth's argument that the exhaustion requirement is inapposite to his case because the administrative process could not award him the monetary relief he sought (money then being the only relief still requested).
trative [redress]" as is available; one "exhausts" processes, not forms of relief, and the statute provides that one must. Second, statutory history confirms the suggestion that Congress meant to require procedural exhaustion regardless of the fit between a prisoner's prayer for relief and the administrative remedies possible. Before § 1997e(a) was amended by the 1995 Act, a court had discretion (though no obligation) to require a state inmate to exhaust "such ... remedies as are available," but only if they were "plain, speedy, and effective." That scheme is now a thing of the past, for the amendments eliminated both the discretion to dispense with administrative exhaustion and the condition that the remedy be "plain, speedy, and effective" before exhaustion could be required. The significance of deleting that condition is apparent in light of McCarthy v. Madigan, 503 U. S. 140. In holding that the preamended version of § 1997e(a) did not require exhaustion by those seeking only money damages when money was unavailable at the administrative level, id., at 149-151, the McCarthy Court reasoned in part that only a procedure able to provide money damages would be "effective" within the statute's meaning, id., at 150. It has to be significant that Congress removed the very term, "effective," the McCarthy Court had previously emphasized in reaching the result Booth now seeks, and the fair inference to be drawn is that Congress meant to preclude the McCarthy result. Congress's imposition of an obviously broader exhaustion requirement makes it highly implausible that it meant to give prisoners a strong inducement to skip the administrative process simply by limiting prayers for relief to money damages not offered through administrative grievance mechanisms. Pp. 736-741.
Nancy Winkelman argued the cause for petitioner. With her on the briefs were Joseph T. Lukens and Ralph N. Sianni.
Gerald J. Pappert, First Deputy Attorney General of Pennsylvania, argued the cause for respondents. With him on the brief were D. Michael Fisher, Attorney General, John G. Knorr III, Chief Deputy Attorney General, and Gwendolyn T. Mosley and Calvin R. Koons, Senior Deputy Attorneys General.
*Briefs of amici curiae urging reversal were filed for the American Civil Liberties Union et al. by David C. Fathi, Elizabeth Alexander, Margaret Winter, Daniel L. Greenberg, John Boston, and Alphonse A. Gerhardstein; for the Association of the Bar of the City of New York by Michael B. Mushlin and William J. Rold; and for the Brennan Center for Justice et al. by Robert J. Lukens, Richard P. Weishaupt, and Jonathan M. Stein.
A brief of amici curiae urging affirmance was filed for the State of Ohio et al. by Betty D. Montgomery, Attorney General of Ohio, Stephen P. Carney, Associate Solicitor, and Todd R. Marti, Assistant Attorney General, and by the Attorneys General for their respective jurisdictions as follows: Bill Pryor of Alabama, Bruce M. Botelho of Alaska, Janet Napolitano of Arizona, Mark Pryor of Arkansas, Bill Lockyer of California, Ken Salazar of Colorado, Richard Blumenthal of Connecticut, M. Jane Brady of Delaware, Robert R. Rigsby of the District of Columbia, Robert A. Butterworth of Florida, Thurbert E. Baker of Georgia, John F. Tarantino of Guam, Earl I. Anzai of Hawaii, Alan Lance of Idaho, James E. Ryan of Illinois, Karen Freeman-Wilson of Indiana, Thomas J. Miller of Iowa, Carla J. Stovall of Kansas, Albert B. Chandler III of Kentucky, Richard P. Ieyoub of Louisiana, G. Steven Rowe of Maine, J. Joseph Curran, Jr., of Maryland, Thomas F. Reilly of Massachusetts, Jennifer M. Granholm of Michigan, Mike Hatch of Minnesota, Mike Moore of Mississippi, Jeremiah W (Jay) Nixon of Missouri, Mike McGrath of Montana, Don Stenberg of Nebraska, Frankie Sue Del Papa of Nevada, Philip T. McLaughlin of New Hampshire, John J. Farmer, Jr., of New Jersey, Patricia A. Madrid of New Mexico, Eliot Spitzer of New York, Roy Cooper of North Carolina, Wayne Stenehjem of North Dakota, W A. Drew Edmondson of Oklahoma, Hardy Myers of Oregon, Sheldon Whitehouse of Rhode Island, Charles M. Condon of South Carolina, Mark Barnett of South Dakota, Paul G. Summers of Tennessee, John Cornyn of Texas, Mark L. Shurtleff of Utah, William H. Sorrell of Vermont, Mark L. Earley of Virginia, Iver A. Stridiron of the Virgin Islands, Christine Q Gregoire of Washington, and Gay Woodhouse of Wyoming.
"such administrative remedies as are available" before suing over prison conditions. The question is whether an inmate seeking only money damages must complete a prison administrative process that could provide some sort of relief on the complaint stated, but no money. We hold that he must.
Petitioner, Timothy Booth, was an inmate at the State Correctional Institution at Smithfield, Pennsylvania, when he began this action under Rev. Stat. § 1979, 42 U. S. C. § 1983, in the United States District Court for the Middle District of Pennsylvania. He claimed that respondent corrections officers at Smithfield violated his Eighth Amendment right to be free from cruel and unusual punishment by assaulting him, bruising his wrists in tightening and twisting handcuffs placed upon him, throwing cleaning material in his face, and denying him medical attention to treat ensuing injuries. Booth sought various forms of injunctive relief, including transfer to another prison, as well as several hundred thousand dollars in money damages.
1 The Commonwealth has since modified its grievance scheme to permit awards of money. App. 60.
abuse he later alleged in his action. Id., at 10-14. He did not, however, go beyond the first step, and never sought intermediate or final administrative review after the prison authority denied relief.
Booth's failure to avail himself of the later stages of the administrative process led the District Court to dismiss the complaint without prejudice for failure to exhaust "administrative remedies ... available" within the meaning of 42 U. S. C. § 1997e(a) (1994 ed., Supp. V). See App. to Pet. for Cert. 38a. The Court of Appeals for the Third Circuit affirmed, 206 F.3d 289 (2000), rejecting Booth's argument that the statutory exhaustion requirement is inapposite to his case simply because the Commonwealth's administrative process could not award him the monetary relief he sought (money then being the only relief still requested, since Booth's transfer to another institution had mooted his claims for injunctive orders).2 Although the Third Circuit acknowledged that several other Courts of Appeals had held the exhaustion requirement subject to exception when the internal grievance procedure could not provide an inmateplaintiff with the purely monetary relief requested in his federal action, see, e. g., Whitley v. Hunt, 158 F.3d 882 (CA5 1998); Lunsford v. Jumao-As, 155 F.3d 1178 (CA9 1998); Garrett v. Hawk, 127 F.3d 1263 (CAlO 1997), the court found no such exception in the statute, 206 F. 3d, at 299-300; accord, Freeman v. Francis, 196 F.3d 641 (CA6 1999); Alexander v. Hawk, 159 F.3d 1321 (CAll 1998). We granted certiorari to address this conflict among the Circuits, 531 U. S. 956 (2000), and we now affirm.
2 There is some uncertainty, probably stemming in part from the ambiguity of Booth's pro se filings in District Court, as to whether all of Booth's claims for relief other than money damages became moot when he was transferred. See Brief for Petitioner 12, n. 7; Brief for United States as Amicus Curiae 10, n. 2. We assume for present purposes that only Booth's claims for money damages remain.
"[n]o action shall be brought with respect to prison conditions under section 1983 of this title, or any other Federal law, by a prisoner confined in any jail, prison, or other correctional facility until such administrative remedies as are available are exhausted."
The meaning of the phrase "administrative remedies ... available" is the crux of the case, and up to a point the parties approach it with agreement. Neither of them denies that some redress for a wrong is presupposed by the statute's requirement of an "available" "remed[y]"; neither argues that exhaustion is required where the relevant administrative procedure lacks authority to provide any relief or to take any action whatsoever in response to a complaint.4 The dispute here, then, comes down to whether or not a remedial scheme is "available" where, as in Pennsylvania, the administrative process has authority to take some action in response to a complaint, but not the remedial action an inmate demands to the exclusion of all other forms of redress.
3110 Stat. 1321, as renumbered and amended.
4 Without the possibility of some relief, the administrative officers would presumably have no authority to act on the subject of the complaint, leaving the inmate with nothing to exhaust. The parties do not dispute that the state grievance system at issue in this case has authority to take some responsive action with respect to the type of allegations Booth raises.
the matter out of court are slim. See Reply Brief for Petitioner 16. The prisoner would be clearly burdened, while the government would obtain little or no value in return. The respondents, however, also have something to say. They argue that requiring exhaustion in these circumstances would produce administrative results that would satisfy at least some inmates who start out asking for nothing but money, since the very fact of being heard and prompting administrative change can mollify passions even when nothing ends up in the pocket. And one may suppose that the administrative process itself would filter out some frivolous claims and foster better-prepared litigation once a dispute did move to the courtroom, even absent formal factfinding. Although we have not accorded much weight to these possibilities in the past, see McCarthy v. Madigan, 503 U. S. 140, 155-156 (1992), Congress, as we explain below, may well have thought we were shortsighted. See infra, at 739-741. In any event, the practical arguments for exhaustion at least suffice to refute Booth's claim that no policy considerations justify respondents' position. The upshot is that pragmatism is inconclusive.
tained")). So far so good, but Booth then claims to be able to infer with particularity that when a prisoner demands money damages as the sole means to compensate his injuries, a grievance system without that relief offers no "available" "remed[y]." The general definitions, however, just do not entail such a specific conclusion.
It strikes us that the same definitions get the respondent corrections officers and their amicus the United States closer to firm ground for their assertion that the phrase "such administrative remedies as are available" naturally requires a prisoner to exhaust the grievance procedures offered, whether or not the possible responses cover the specific relief the prisoner demands. See Brief for Respondents 21. The United States tracks Booth in citing Webster's Third New International Dictionary to define "remedy" as "the legal means to recover a right or to prevent or obtain redress for a wrong" and "available" as "capable of use for the accomplishment of a purpose." Webster's Third New International Dictionary, supra, at 150, 1920. But this exercise in isolated definition is ultimately inconclusive, for, depending on where one looks, "remedy" can mean either specific relief obtainable at the end of a process of seeking redress, or the process itself, the procedural avenue leading to some relief. See Black's Law Dictionary 1296 (7th ed. 1999) (defining "remedy" alternatively as "[t]he means of enforcing a right or preventing or redressing a wrong," or as "REMEDIAL ACTION .... Cf. RELIEF").
parties agree), the word "exhausted" has a decidedly procedural emphasis. It makes sense only in referring to the procedural means, not the particular relief ordered. It would, for example, be very strange usage to say that a prisoner must "exhaust" an administrative order reassigning an abusive guard before a prisoner could go to court and ask for something else; or to say (in States that award money damages administratively) that a prisoner must "exhaust" his damages award before going to court for more. How would he "exhaust" a transfer of personnel? Would he have to spend the money to "exhaust" the monetary relief given him? It makes no sense to demand that someone exhaust "such administrative [redress]" as is available; one "exhausts" processes, not forms of relief, and the statute provides that one must.
A second consideration, statutory history, confirms the suggestion that Congress meant to require procedural exhaustion regardless of the fit between a prisoner's prayer for relief and the administrative remedies possible. Before § 1997e(a) was amended by the Act of 1995, a court had discretion (though no obligation) to require a state inmate to exhaust "such ... remedies as are available," but only if those remedies were "plain, speedy, and effective." 42 U. S. C. § 1997e(a) (1994 ed.). That scheme, however, is now a thing of the past, for the amendments eliminated both the discretion to dispense with administrative exhaustion and the condition that the remedy be "plain, speedy, and effective" before exhaustion could be required.
exhaustion requirement for Bivens actions. See Bivens v. Six Unknown Fed. Narcotics Agents, 403 U. S. 388 (1971). It proposed § 1997e(a) as a model, on the assumption that the provision required exhaustion by those seeking nothing but money damages even when money was unavailable at the administrative level. We understood the effect of § 1997e(a) to be quite different, however. See 503 U. S., at 149-151. In holding that exhaustion was not required, we reasoned in part from the language of § 1997e(a) that required an "effective" administrative remedy as a precondition to exhaustion. Id., at 150. When a prisoner sought only money damages, we indicated, only a procedure able to provide money damages would be "effective" within the meaning of the statute. Ibid. ("[I]n contrast to the absence of any provision for the award of money damages under the Bureau's general grievance procedure, the statute conditions exhaustion on the existence of 'effective administrative remedies' "); see also id., at 156 (REHNQUIST, C. J., joined by SCALIA and THOMAS, JJ., concurring in judgment) ("[I]n cases ... where prisoners seek monetary relief, the Bureau's administrative remedy furnishes no effective remedy").
of an obviously broader exhaustion requirement makes it highly implausible that it meant to give prisoners a strong inducement to skip the administrative process simply by limiting prayers for relief to money damages not offered through administrative grievance mechanisms.
Thus, we think that Congress has mandated exhaustion clearly enough, regardless of the relief offered through administrative procedures.6 Cf. McCarthy, 503 U. S., at 144 ("Where Congress specifically mandates, exhaustion is required"). We accordingly affirm the judgment of the Third Circuit.
courts' discretion to excuse exhaustion when it would not be "appropriate and in the interests of justice." Compare 42 U. S. C. § 1997e(a) (1994 ed., Supp. V) with 42 U. S. C. § 1997e(a) (1994 ed.).
6 That Congress has mandated exhaustion in either case defeats the argument of Booth and supporting amici that this reading of § 1997e (1994 ed., Supp. V) is at odds with traditional doctrines of administrative exhaustion, under which a litigant need not apply to an agency that has "no power to decree ... relief," Reiter v. Cooper, 507 U. S. 258, 269 (1993), or need not exhaust where doing so would otherwise be futile. See Brief for Petitioner 24-27; Brief for Brennan Center for Justice et al. as Amici Curiae. Without getting into the force of this claim generally, we stress the point (which Booth acknowledges, see Reply Brief for Petitioner 4) that we will not read futility or other exceptions into statutory exhaustion requirements where Congress has provided otherwise. See McCarthy v. Madigan, 503 U. S. 140, 144 (1992); cf. Weinberger v. Salfi, 422 U. S. 749, 766-767 (1975). Here, we hold only that Congress has provided in § 1997e(a) that an inmate must exhaust irrespective of the forms of relief sought and offered through administrative avenues.


(12) exercise such other powers and perform such other functions and duties as may be prescribed by law.
(b) The behavioral sciences regulatory board, in addition to any other penalty, may assess an administrative penalty, after notice and an opportunity to be heard, against a licensee or registrant for a violation of any of the provisions of the licensure of psychologists act of the state of Kansas, the professional counselors licensure act, K.S.A. 65-6301 to 65-6320, inclusive, and amendments thereto, K.S.A. 74-5361 to 74-5374, inclusive, and K.S.A. 2012 Supp. 74-5375, and amendments thereto, the marriage and family therapists licensure act or the addictions counselor licensure act in an amount not to exceed $1,000. All fines assessed and collected under this section shall be remitted to the state treasurer in accordance with the provisions of K.S.A. 75-4215, and amendments thereto. Upon receipt of each such remittance, the state treasurer shall deposit the entire amount in the state treasury to the credit of the state general fund.
(c) If an order of the behavioral sciences regulatory board is adverse to a licensee or registrant of the board, the costs shall be charged to such person as in ordinary civil actions in the district court in an amount not to exceed $200. The board shall pay any additional costs and, if the board is the unsuccessful party, the costs shall be paid by the board. Witness fees and costs may be taxed in accordance with statutes governing taxation of witness fees and costs in the district court.
History: L. 1980, ch. 242, § 7; L. 1986, ch. 299, § 42; L. 1987, ch. 315, § 17; L. 1991, ch. 114, § 15; L. 1992, ch. 184, § 7; L. 1996, ch. 153, § 43; L. 2004, ch. 16, § 5; L. 2010, ch. 45, § 15; July 1, 2011.