The genetics of extreme microgeographic adaptation: an integrated approach identifies a major gene underlying leaf trichome divergence in Yellowstone Mimulus guttatus.

Microgeographic adaptation provides a particularly interesting context for understanding the genetic basis of phenotypic divergence and may also present unique empirical challenges. In particular, plant adaptation to extreme soil mosaics may generate barriers to gene flow or shifts in mating system that confound simple genomic scans for adaptive loci. Here, we combine three approaches - quantitative trait locus (QTL) mapping of candidate intervals in controlled crosses, population resequencing (PoolSeq) and analyses of wild recombinant individuals - to investigate one trait associated with Mimulus guttatus (yellow monkeyflower) adaptation to geothermal soils in Yellowstone National Park. We mapped a major QTL causing dense leaf trichomes in thermally adapted plants to a <50-kb region of linkage Group 14 (Tr14) previously implicated in trichome divergence between independent M. guttatus populations. A PoolSeq scan of Tr14 region revealed a cluster of six genes, coincident with the inferred QTL peak, with high allele frequency differences sufficient to explain observed phenotypic differentiation. One of these, the R2R3 MYB transcription factor Migut.N02661, is a plausible functional candidate and was also strongly associated (r2  = 0.27) with trichome phenotype in analyses of wild-collected admixed individuals. Although functional analyses will be necessary to definitively link molecular variants in Tr14 with trichome divergence, our analyses are a major step in that direction. They point to a simple, and parallel, genetic basis for one axis of Mimulus guttatus adaptation to an extreme habitat, suggest a broadly conserved genetic basis for trichome variation across flowering plants and pave the way for further investigations of this challenging case of microgeographic incipient speciation.

Fugitive methane emissions from leak-prone natural gas distribution infrastructure in urban environments.

Fugitive emissions from natural gas systems are the largest anthropogenic source of the greenhouse gas methane (CH4) in the U.S. and contribute to the risk of explosions in urban environments. Here, we report on a survey of CH4 emissions from 100 natural gas leaks in cast iron distribution mains in Metro Boston, MA. Direct measures of CH4 flux from individual leaks ranged from 4.0 - 2.3 × 10(4) g CH4•day(-1). The distribution of leak size is positively skewed, with 7% of leaks contributing 50% of total CH4 emissions measured. We identify parallels in the skewed distribution of leak size found in downstream systems with midstream and upstream stages of the gas process chain. Fixing 'superemitter' leaks will disproportionately stem greenhouse gas emissions. Fifteen percent of leaks surveyed qualified as potentially explosive (Grade 1), and we found no difference in CH4 flux between Grade 1 leaks and all remaining leaks surveyed (p = 0.24). All leaks must be addressed, as even small leaks cannot be disregarded as 'safely leaking.' Key methodological impediments to quantifying and addressing the impacts of leaking natural gas distribution infrastructure involve inconsistencies in the manner in which gas leaks are defined, detected, and classified. To address this need, we propose a two-part leak classification system that reflects both the safety and climatic impacts of natural gas leaks.

Phenotypic and genetic differentiation among yellow monkeyflower populations from thermal and non-thermal soils in Yellowstone National Park.

In flowering plants, soil heterogeneity can generate divergent natural selection over fine spatial scales, and thus promote local adaptation in the absence of geographic barriers to gene flow. Here, we investigate phenotypic and genetic differentiation in one of the few flowering plants that thrives in both geothermal and non-thermal soils in Yellowstone National Park (YNP). Yellow monkeyflowers (Mimulus guttatus) growing at two geothermal ("thermal") sites in YNP were distinct in growth form and phenology from paired populations growing nearby (<500 m distant) in non-thermal soils. In simulated thermal and non-thermal environments, thermal plants remained significantly divergent from non-thermal plants in vegetative, floral, mating system, and phenological traits. Plants from both thermal populations flowered closer to the ground, allocated relatively more to sexual reproduction, were more likely to initiate flowering under short daylengths, and made smaller flowers that could efficiently self-fertilize without pollinators. These shared differences are consistent with local adaptation to life in the ephemeral window for growth and reproduction created by winter and spring snowmelt on hot soils. In contrast, habitat type (thermal vs. non-thermal) explained little of the genetic variation at neutral markers. Instead, we found that one thermal population (Agrostis Headquarters; AHQ-T) was strongly differentiated from all other populations (all F (ST) > 0.34), which were only weakly differentiated from each other (all F (ST) < 0.07). Phenotypic differentiation of thermal M. guttatus, but little population genetic evidence of long-term ecotypic divergence, encourages further investigations of the potential for fine-scale adaptation and reproductive isolation across the geothermal gradient in Yellowstone.

Halofuginone and other febrifugine derivatives inhibit prolyl-tRNA synthetase.

Febrifugine, the bioactive constituent of one of the 50 fundamental herbs of traditional Chinese medicine, has been characterized for its therapeutic activity, though its molecular target has remained unknown. Febrifugine derivatives have been used to treat malaria, cancer, fibrosis and inflammatory disease. We recently demonstrated that halofuginone (HF), a widely studied derivative of febrifugine, inhibits the development of T(H)17-driven autoimmunity in a mouse model of multiple sclerosis by activating the amino acid response (AAR) pathway. Here we show that HF binds glutamyl-prolyl-tRNA synthetase (EPRS), inhibiting prolyl-tRNA synthetase activity; this inhibition is reversed by the addition of exogenous proline or EPRS. We further show that inhibition of EPRS underlies the broad bioactivities of this family of natural product derivatives. This work both explains the molecular mechanism of a promising family of therapeutics and highlights the AAR pathway as an important drug target for promoting inflammatory resolution.