Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Agrarian Dreams, Agricultural Realities: Agricultural land conversion in Mexico's Chihuahuan Desert

This dissertation examines the drivers and socioeconomic process of the conversion of rangeland to irrigated crops in Janos County, Chihuahua since 1970. The research was motivated by a desire to understand why irrigated agriculture was expanding in this site when there were no such expansions in adjacent regions. I analyze the historical roots of agricultural expansion as well as the contemporary social and economic dynamics that propel it today. Data came from 166 interviews with landowners, ex-landowners, laborers, and local officials, as well as from historical land records. Results reveal the importance Mexico’s national land reform (~1920-1992) in breaking up large ranches and creating opportunities for small farms to become established, even if many of those small farms—especially on ejidos—ultimately failed. I attribute the majority of rangeland-to-cropland conversion to Mennonites, whose commodity farms have proliferated through both in-migration and capitalist investment of agricultural profits. My research contributes to the wide-ranging literature on Mexico’s ejido system through the analysis of dynamics on the arid lands ejidos in Janos County. The Janos ejidos differ from the preponderance of cases in the literature in that they were founded through very different mechanisms and have seen far higher rates of land sales and consolidation. I contribute to the literature on agricultural frontiers by discussing agricultural expansion in arid rangelands rather than in tropical forests, where most of the literature is centered. The contrast between stagnating agriculture on the ejidos and expanding agriculture by Mennonites reveals both the importance of capital access in desert farming and the prominent role that social and cultural capital play in improving access to agriculture. In Janos, addressing the ‘agrarian question’ entails a close examination of capital access as well as intragroup social dynamics. Commercial cattle grazing has been the dominant land use there for at least 300 years, though the percentage of land under crops has expanded significantly in recent decades, irrigated with groundwater from a declining aquifer. The proliferation of irrigated agriculture has roots in Mexico’s national land reform, which ran nearly from the end of the Revolution in 1920 until 1992. The land reform fractured the vast cattle ranches that had previously dominated Janos County and redistributed a third of the land area in the form of 14 ejidos. The land reform also incentivized ranchers to sell land rather than have it expropriated by the government, which enabled groups of Mennonites from central Chihuahua to buy thousands of hectares at a time starting in the 1950s. Those parcels became the first four Mennonite colonies in Janos County and the hubs of ongoing cropland expansion.The process of ejido formation in Janos County was different than in most studies of central and southern Mexico, with profound impacts for land use and rights ownership. Ejidos here were not formed through restitution of land rights to long-term residents, indigenous communities, or even occupiers. Instead, land rights on new ejidos were given to landless laborers who had signed petitions demanding land through the land reform process, laborers who were most often living more than hundred kilometers from Janos County and had never been there. The freshly minted ejidatarios who came to Janos County to begin their new agrarian lives lacked the equipment, the investment capital, the farming expertise, and the social relations with each other needed to establish farms. While government support for these communities was significant, it was only sporadically sufficient to establish agricultural livelihoods. Out-migration and land sales were rampant, particularly after Mexico’s neoliberal policy reforms of the late 1980s and 1990s. There has been significant consolidation of land control on the ejidos since the 1990s, which has facilitated the ability of some households to earn a modest living from cattle or crops. On nearly every ejido, there remains land officially designated for farming that is still used only for cattle grazing.Founders of the first four Mennonite colonies in Janos County had come from Mennonite communities in west-central Chihuahua, and those communities had been founded by Mennonites immigrating from Canada in the 1920s. Mennonites in Janos County are Mexican citizens or dual Mexican-Canadian citizens but are in nearly every way deliberately distinct from mainstream Mexican society. They still speak Spanish as a second language, if at all, and they live in clearly defined colonies with their own churches, schools, businesses, and minute governmental institutions. They are also farmers first and foremost, though there is some economic diversification. Mennonite settlers arrived to Janos with sufficient economic means to establish irrigated farms – mostly modest – and construct functioning community centers with minimal state support. Mennonite colonies are ethnic enclaves that maintain high stocks of social and cultural capital that improve access to farming and foster loyalty to the home community and to farming as a livelihood. Social practices of cooperation and preferential treatment reduce the economic burden of establishing new farms or expanding existing farms, such as sharing farm machinery and paying each other for land or expensive services in annual installments without interest. Mennonites also have their own sources of formal and informal credit that are difficult for outsiders to access. The Mennonite agricultural access regime has enabled farmers to gradually intensify and expand their farming operations over time. Mennonites now routinely tap into international markets to grow genetically modified cotton, in addition to chili peppers, onions, and other crops that are planted, weeded, and harvested by migrant workers from southern and central Mexico.Agricultural production in my focal communities was always of ubiquitous commodities produced primarily for the market, but since the 1990s there has been something of an agrarian transformation underway. The area of irrigated crops has expanded rapidly, driven in part by economic differentiation of farmers and consolidation of landownership. The national neoliberal policy changes in the 1990s enabled these changes, as they served to increase the costs of agricultural production, significantly alter credit access, open new agricultural markets, and legalize the sale and rental of ejido land rights. While rising production costs drove some ejidatario and Mennonite farmers to sell out and migrate, new markets and sources of credit enabled wealthier Mennonite farmers to intensify and expand their operations. Increased farm profits among the emerging Mennonite elite were plowed back into purchases of ejido parcels and new blocks of ranchland outside the original colonies. The expansion drove up property values, further incentivizing ejidatarios and ranchers alike to sell land to Mennonites. High property values and competition for land are major barriers to entry for young would-be farmers, breeding new concerns over social justice and community values. Meanwhile, irrigated agriculture continues to expand outward from the original Mennonite colonies and the aquifer continues to fall

Agrarian Dreams, Agricultural Realities: Agricultural Land Conversion in Mexico's Chihuahuan Desert

This dissertation examines the drivers and socioeconomic process of the conversion of rangeland to irrigated crops in Janos County, Chihuahua since 1970. The research was motivated by a desire to understand why irrigated agriculture was expanding in this site when there were no such expansions in adjacent regions. I analyze the historical roots of agricultural expansion as well as the contemporary social and economic dynamics that propel it today. Data came from 166 interviews with landowners, ex-landowners, laborers, and local officials, as well as from historical land records. Results reveal the importance Mexico’s national land reform (~1920-1992) in breaking up large ranches and creating opportunities for small farms to become established, even if many of those small farms—especially on ejidos—ultimately failed. I attribute the majority of rangeland-to-cropland conversion to Mennonites, whose commodity farms have proliferated through both in-migration and capitalist investment of agricultural profits. My research contributes to the wide-ranging literature on Mexico’s ejido system through the analysis of dynamics on the arid lands ejidos in Janos County. The Janos ejidos differ from the preponderance of cases in the literature in that they were founded through very different mechanisms and have seen far higher rates of land sales and consolidation. I contribute to the literature on agricultural frontiers by discussing agricultural expansion in arid rangelands rather than in tropical forests, where most of the literature is centered. The contrast between stagnating agriculture on the ejidos and expanding agriculture by Mennonites reveals both the importance of capital access in desert farming and the prominent role that social and cultural capital play in improving access to agriculture. In Janos, addressing the ‘agrarian question’ entails a close examination of capital access as well as intragroup social dynamics. Commercial cattle grazing has been the dominant land use there for at least 300 years, though the percentage of land under crops has expanded significantly in recent decades, irrigated with groundwater from a declining aquifer. The proliferation of irrigated agriculture has roots in Mexico’s national land reform, which ran nearly from the end of the Revolution in 1920 until 1992. The land reform fractured the vast cattle ranches that had previously dominated Janos County and redistributed a third of the land area in the form of 14 ejidos. The land reform also incentivized ranchers to sell land rather than have it expropriated by the government, which enabled groups of Mennonites from central Chihuahua to buy thousands of hectares at a time starting in the 1950s. Those parcels became the first four Mennonite colonies in Janos County and the hubs of ongoing cropland expansion. The process of ejido formation in Janos County was different than in most studies of central and southern Mexico, with profound impacts for land use and rights ownership. Ejidos here were not formed through restitution of land rights to long-term residents, indigenous communities, or even occupiers. Instead, land rights on new ejidos were given to landless laborers who had signed petitions demanding land through the land reform process, laborers who were most often living more than hundred kilometers from Janos County and had never been there. The freshly minted ejidatarios who came to Janos County to begin their new agrarian lives lacked the equipment, the investment capital, the farming expertise, and the social relations with each other needed to establish farms. While government support for these communities was significant, it was only sporadically sufficient to establish agricultural livelihoods. Out-migration and land sales were rampant, particularly after Mexico’s neoliberal policy reforms of the late 1980s and 1990s. There has been significant consolidation of land control on the ejidos since the 1990s, which has facilitated the ability of some households to earn a modest living from cattle or crops. On nearly every ejido, there remains land officially designated for farming that is still used only for cattle grazing. Founders of the first four Mennonite colonies in Janos County had come from Mennonite communities in west-central Chihuahua, and those communities had been founded by Mennonites immigrating from Canada in the 1920s. Mennonites in Janos County are Mexican citizens or dual Mexican-Canadian citizens but are in nearly every way deliberately distinct from mainstream Mexican society. They still speak Spanish as a second language, if at all, and they live in clearly defined colonies with their own churches, schools, businesses, and minute governmental institutions. They are also farmers first and foremost, though there is some economic diversification. Mennonite settlers arrived to Janos with sufficient economic means to establish irrigated farms – mostly modest – and construct functioning community centers with minimal state support. Mennonite colonies are ethnic enclaves that maintain high stocks of social and cultural capital that improve access to farming and foster loyalty to the home community and to farming as a livelihood. Social practices of cooperation and preferential treatment reduce the economic burden of establishing new farms or expanding existing farms, such as sharing farm machinery and paying each other for land or expensive services in annual installments without interest. Mennonites also have their own sources of formal and informal credit that are difficult for outsiders to access. The Mennonite agricultural access regime has enabled farmers to gradually intensify and expand their farming operations over time. Mennonites now routinely tap into international markets to grow genetically modified cotton, in addition to chili peppers, onions, and other crops that are planted, weeded, and harvested by migrant workers from southern and central Mexico. Agricultural production in my focal communities was always of ubiquitous commodities produced primarily for the market, but since the 1990s there has been something of an agrarian transformation underway. The area of irrigated crops has expanded rapidly, driven in part by economic differentiation of farmers and consolidation of landownership. The national neoliberal policy changes in the 1990s enabled these changes, as they served to increase the costs of agricultural production, significantly alter credit access, open new agricultural markets, and legalize the sale and rental of ejido land rights. While rising production costs drove some ejidatario and Mennonite farmers to sell out and migrate, new markets and sources of credit enabled wealthier Mennonite farmers to intensify and expand their operations. Increased farm profits among the emerging Mennonite elite were plowed back into purchases of ejido parcels and new blocks of ranchland outside the original colonies. The expansion drove up property values, further incentivizing ejidatarios and ranchers alike to sell land to Mennonites. High property values and competition for land are major barriers to entry for young would-be farmers, breeding new concerns over social justice and community values. Meanwhile, irrigated agriculture continues to expand outward from the original Mennonite colonies and the aquifer continues to fall

Changing Agro-Pastoral Livelihoods under Collective and Private Land Use in Xinjiang, China

After the founding of P. R. China, land use in rural China was organized under two successive paradigms: state-directed collectivization from 1958–1984 (the Collective Era), and privatization after 1984 (the Household Land Contract Period, HLCP). Taking Nileke County of Xinjiang as a case study, this research analyzed the livelihood changes of agro-pastoralists over the two periods using quantitative household livelihood assets—financial, physical, natural, human, and social capital—as indicators. Using annual series data of the five livelihood capitals, a comprehensive livelihood assets index (CLAI) was calculated by two-stage factor analysis. Higher CLAI scores meant better living and reduced poverty for agro-pastoralists. Quantitative results were validated and detailed with semi-structured household interviews. The results showed that CLAI slightly increased during the HLCP in comparison to the Collective Era, mainly due to increases in financial and physical capital. In contrast, natural and social capital showed downward trends, indicating that alleviation of poverty came at the cost of natural resources and social justice. Natural capital was the main contributor to agro-pastoralist livelihoods during the Collective Era, but diminished and was replaced by financial capital during the HLCP. Based on the findings, we put forward policy suggestions to improve community land management and sustainable livelihoods as part of future poverty alleviation efforts

Grazing exclusion reduced soil respiration but increased its temperature sensitivity in a Meadow Grassland on the Tibetan Plateau

Understanding anthropogenic influences on soil respiration (R-s) is critical for accurate predictions of soil carbon fluxes, but it is not known how R-s responds to grazing exclusion (GE). Here, we conducted a manipulative experiment in a meadow grassland on the Tibetan Plateau to investigate the effects of GE on R-s. The exclusion of livestock significantly increased soil moisture and above-ground biomass, but it decreased soil temperature, microbial biomass carbon (MBC), and R-s. Regression analysis indicated that the effects of GE on R-s were mainly due to changes in soil temperature, soil moisture, and MBC. Compared with the grazed blocks, GE significantly decreased soil carbon release by 23.6% over the growing season and 21.4% annually, but it increased the temperature sensitivity (Q(10)) of R-s by 6.5% and 14.2% for the growing season and annually respectively. Therefore, GE may reduce the release of soil carbon from the Tibetan Plateau, but under future climate warming scenarios, the increases in Q(10) induced by GE could lead to increased carbon emissions

Save water or save wildlife? Water use and conservation in the central Sierran foothill oak woodlands of California, USA

More frequent drought is projected for California. As water supplies constrict, and urban growth and out-migration spread to rural areas, trade-offs in water use for agriculture, biodiversity conservation, fire hazard reduction, residential development, and quality of life will be exacerbated. The California Black Rail (Laterallus jamaicensis coturniculus), state listed as “Threatened,” depends on leaks from antiquated irrigation district irrigation systems for much of its remnant small wetland habitat in the north central Sierra Nevada foothills. Residents of the 1295 km² foothill habitat distribution of the Black Rail were surveyed about water use. Results show that the most Black Rail habitat is owned by those purchasing water to irrigate pasture, a use that commonly creates wetlands from leaks and tailwater. Promoting wildlife, agricultural production, and preventing wildfire are common resident goals that call for abundant and inexpensive water; social and economic pressures encourage reduction in water use and the repair of leaks that benefit wildlife and greenery. Broad inflexible state interventions to curtail water use are likely to create a multitude of unintended consequences, including loss of biodiversity and environmental quality, and alienation of residents as valued ecosystem services literally dry up. Adaptive and proactive policies are needed that consider the linkages in the social-ecological system, are sensitive to local conditions, prevent landscape dewatering, and recognize the beneficial use of water to support ecosystem services such as wildlife habitat. Much Black Rail habitat is anthropogenic, created at the nexus of local governance, plentiful water, agricultural practices, historical events, and changing land uses. This history should be recognized and leveraged rather than ignored in a rush to “save” water by unraveling the social-ecological system that created the landscape. Policy and governance needs to identify and prioritize habitat areas to maintain during drought.This project was funded as part of the NSF Coupled Human Natural Systems Program, Project Award Number 1115069, Wetlands in a Working Landscape, with Professor Steve Beissinger as Principal Investigator. J.L. Oviedo’s involvement in this study was also funded by the Salvador de Madariaga program (grant number PRX16/00452) of the Spanish Ministry of Education, Culture and Sports.Peer reviewe

Assessing impacts of social-ecological diversity on resilience in a wetland coupled human and natural system: Data release

[Methods] We mapped all emergent wetlands > 5×5 m within our study area—California’s Sierra Nevada foothills EPA zone III eco-region in Yuba, Nevada, and southern Butte countieso of California. Mapping was done by manually interpreting summer 2013 GeoEye-1 0.4 m imagery in Google Earth 7.1.5. Areas covered by hydrophytes (Typha spp., Scirpus spp., Juncus effusus, Leersia oryzoides, or various sedges) were considered wetland. We included hydrophytes that appeared seasonally dried; if green vegetation was present along the wetland-upland transition zone, we buffered 5 m into it. Open water and rice were excluded. If imagery was ambiguous, we used Google Earth imagery from adjacent years to help distinguish if a wetland was present. Each wetland’s geomorphology was classified as slope (shallow hillside flow), pond fringe, fluvial, rice fringe, irrigation ditch, or waterfowl impoundment. We combined historic imagery and field data to determine the water sources. We surveyed 237 wetlands for occupancy of Black Rails up to three times each summer from 2012–2016 using established broadcast survey methods (for details see Richmond et al. 2010). To assess the effects of water source on wetland hydrology, we resurveyed wetlands for 14 periods: in the early wet season (January 8–27), late wet season (March 22–25), early dry season (May 17–June 20), and late dry season (July 15–August 15) from summer 2013–2016. At each visit we walked throughout the wetland with a map of aerial imagery and recorded the percent wetness (areal percent of wetland saturated with water). We trapped mosquitoes at 63 wetlands from June–October, 2012–2014 (4710 trap/nights) and estimated WNV prevalence (probability of a mosquito testing positive for WNV) with genetic testing. We estimated WNV transmission risk at each wetland as the mean abundance of WNV-infected Culex spp. (the main WNV vectors) per trap/night. [Usage Notes] Note that wetland data is not a comprehensive list of all wetlands in the region. Missing values for black rail occupancy in some years or visits within years are delineated withTheory posits that resilience of ecosystems increases when there is a diversity of agents (e.g., species) and linkages between them. If ecosystems are conceptualized as components of “coupled human and natural systems”, then a corollary would be that novel types of human-induced diversity may also foster resilience. We explored this hypothesis by studying how socially created diversity mediated the impact of a historically severe drought on a network of wetlands in the foothills of the California Sierra Nevada containing a metapopulation of the threatened California Black Rail (Laterallus jamaicensis coturniculus). We examined how (1) diversity in motivations for land ownership affected use of irrigation water and response to drought, (2) differences in natural and irrigated water sources affected wetland drying in response to drought, and (3) these processes affected the persistence of rails and the transmission risk of West Nile virus, an emerging infectious disease that threatens people and rails. Wetlands were mostly fed by inefficiencies and leaks from the irrigation system. Wetlands with both natural and irrigated water sources were larger, wetter, and likelier to persist through drought because these two sources showed response diversity by drying at different times. Wetlands with diverse water sources also provided the best habitat for the California Black Rail, and irrigation appeared responsible for its persistence through the drought. Irrigation increased WNV transmission risk by increasing the quantity, but not the quality, of wetland habitats for mosquitoes. The impacts of social diversity were more ambiguous, with redundancy prevalent. However, profit-motivated landowners provided wetlands more irrigation during non-drought conditions, while other landowner types were more likely to continue providing irrigation during drought. This dataset provides the wetland, California Black Rail, and West Nile virus data that support the findings of this study. Partial social and geospatial data are available by emailing the first author upon request, excluding some information that would make respondents identifiable.Sierra Foothills Audubon Society. National Science Foundation, Award: CNH-1115069. National Science Foundation, Award: DEB-1051342. Spanish Ministry of Culture and Education’s Salvador de Madariaga Program, Award: PRX16/00452.Peer reviewe

Assessing impacts of social-ecological diversity on resilience in a wetland coupled human and natural system

Theory posits that resilience of ecosystems increases when there is a diversity of agents (e.g., species) and linkages between them. If ecosystems are conceptualized as components of coupled human and natural systems, then a corollary would be that novel types of human-induced diversity may also foster resilience. We explored this hypothesis by studying how socially created diversity mediated the impact of a historically severe drought on a network of wetlands in the foothills of the California Sierra Nevada containing a metapopulation of the threatened California Black Rail (Laterallus jamaicensis coturniculus). We examined how (1) diversity in motivations for land ownership affected use of irrigation water and response to drought; (2) differences in natural and irrigated water sources affected wetland drying in response to drought; and (3) these processes affected the persistence of rails and the transmission risk of West Nile virus (WNV), an emerging infectious disease that threatens people and rails. Wetlands were mostly fed by inefficiencies and leaks from the irrigation system. Wetlands with both natural and irrigated water sources were larger, wetter, and likelier to persist through drought because these two sources showed response diversity by drying at different times. Wetlands with diverse water sources also provided the best habitat for the California Black Rail, and irrigation appeared responsible for its persistence through the drought. Irrigation increased WNV transmission risk by increasing the quantity, but not the quality, of wetland habitats for mosquitoes. The impacts of social diversity were more ambiguous, with redundancy prevalent. However, profit-motivated landowners provided wetlands more irrigation during nondrought conditions, whereas other landowner types were more likely to continue providing irrigation during drought. Our results highlight that conservation in social-ecological systems requires assessing not only the value of historic ecological diversity, but also how novel types of socially induced diversity may benefit ecosystems.We thank the field technicians, landowners, Jerry Tecklin, and Sierra Nevada Foothill Research and Extension Center for making this research possible. We thank the National Science Foundation (DEB-1051342, CNH-1115069), the Spanish Ministry of Culture and Education’s Salvador de Madariaga program (PRX16/00452), and the Sierra Foothills Audubon Society for funding.Peer reviewe

Integrating social and ecological data to model metapopulation dynamics in coupled human and natural systems

Editors’ Note: Papers in this Special Feature are linked online in a virtual table of contents at: www.wiley.com/go/ecologyjournal[EN] Understanding how metapopulations persist in dynamic working landscapes requires assessing the behaviors of key actors that change patches as well as intrinsic factors driving turnover. Coupled human and natural systems (CHANS) research uses a multidisciplinary approach to identify the key actors, processes, and feedbacks that drive metapopulation and landscape dynamics. We describe a framework for modeling metapopulations in CHANS that integrates ecological and social data by coupling stochastic patch occupancy models of metapopulation dynamics with agent-based models of land-use change. We then apply this framework to metapopulations of the threatened black rail (Laterallus jamaicensis) and widespread Virginia rail (Rallus limicola) that inhabit patchy, irrigation-fed wetlands in the rangelands of the California Sierra Nevada foothills. We collected data from five diverse sources (rail occupancy surveys, land-use change mapping, a survey of landowner decision making, climate and reservoir databases, and mosquito trapping and West Nile virus testing) and integrated them into an agent-based stochastic patch occupancy model. We used the model to (1) quantify the drivers of metapopulation dynamics, and the potential interactions and feedbacks among them; (2) test predictions of the behavior of metapopulations in dynamic working landscapes; and (3) evaluate the impact of three policy options on metapopulation persistence (irrigation district water cutbacks during drought, incentives for landowners to create wetlands, and incentives for landowners to protect wetlands). Complex metapopulation dynamics emerged when landscapes functioned as CHANS, highlighting the importance of integrating human activities and other ecological processes into metapopulation models. Rail metapopulations were strongly top-down regulated by precipitation, and the black rail's decade-long decline was caused by the combination of West Nile virus and drought. Theoretical predictions of the two metapopulations’ responses to dynamic landscapes and incentive programs were complicated by heterogeneity in patch quality and CHANS couplings, respectively. Irrigation cutbacks during drought posed a serious extinction risk that neither incentive policy effectively ameliorated