Biology subjects

Leonard, L.

Publications and source records attributed to Leonard, L..

4 recordsLinked to original sources

bioRxiv2025

Mapping of genotype-by-environment interaction loci for Metabolic Syndrome-like traits using the multi-parent Drosophila Synthetic Population Resource determines that main genetic effects are distinct from environment dependent plastic loci

Metabolic Syndrome (MetS) risk, driven by genotype-environment interactions like diet, is rising globally. Due to its genetic and environmental complexity, the genetic architecture and interconnected traits underlying MetS is poorly understood. In Drosophila, genotype-by-diet interactions significantly influence MetS-like traits. This study used the Drosophila Synthetic Population Resource to dissect the genetic architecture of both genotypic and genotype-by-diet interaction effects underlying trait variation. The study hypotheses were: 1) Loci responsible for metabolic phenotypic variation should be shared across traits. 2) Genetic loci responsible for plasticity and epistatic interactions for metabolic traits should also be the loci responsible for the main effects. 3) Genes responsible for variation in metabolic traits should share common functions. Using a round-robin crossing scheme and novel analyses, we mapped additive, dominance, and epistatic loci--some diet-specific, others diet-independent. Main-effect and plastic loci were largely distinct, as were epistatic loci from main-effect loci, highlighting that main genetic effects alone will not explain how genetic variants interact with the environment or the genome to influence disease risk. gene-by-diet or gene-by-gene interactions influencing MetS risk. Further, tremendous cryptic genetic variation for metabolic traits is lurking in natural populations. We explored the function of candidate genes from our study empirically and with bioinformatics. While some of the candidate genes might have been expected, most would not have been identified a priori, thus with this study we have identified many new candidate mechanisms contributing to the genetic and genotype-by-diet interaction effects on MetS variance.

genetics↗

bioRxiv2024

Maladaptation in cereal crop landraces following a soot-producing climate catastrophe

Aerosol-producing global catastrophes such as nuclear war, super-volcano eruption, or asteroid strike, although rare, pose a serious threat to human survival. Light-absorbing aerosols would sharply reduce temperature and solar radiation reaching the earths surface, decreasing crop productivity including for locally adapted traditional crop varieties, i.e. landraces. Here, we test post-catastrophic climate impacts on barley, maize, rice, and sorghum, four crops with extensive landrace cultivation, under a range of nuclear war scenarios that differ in the amount of black carbon aerosol (soot) injected into the climate model. We used a crop growth model to estimate gradients of environmental stressors that drive local adaptation. We then fit genotype environment associations using high density genomic markers with gradient forest offset (GF offset) methods and predicted maladaptation through time. As a validation, we found that our GF models successfully predicted local adaptation of maize landraces in multiple common gardens across Mexico. We found strong concordance between GF offset and disruptions in climate, and landraces of all tested crop species were predicted to be the most maladapted across space and time where soot-induced climate change was the greatest. We further used our GF models to identify landrace varieties best matched to specific post-catastrophic conditions, indicating potential substitutions for agricultural resilience. We found the best landrace genotype was often far away or in another nation, though countries with more climatic diversity had better within-country substitutions. Our results highlight that a soot-producing catastrophe would result in the global maladaptation of landraces and suggest that current landrace adaptive diversity is insufficient for agricultural resilience in the case of the soot scenarios with the greatest change to climate.

evolutionary biology↗

bioRxiv2023

Adaptative Laboratory Evolution reveals biofilm regulating genes as key players in B. subtilis root colonization

Root-associated microorganisms play an important role in plant health, such as plant growth-promoting rhizobacteria from the Bacillus and Pseudomonas genera. Although bacterial consortia including these two genera would represent a promising avenue to efficient biofertilizer formulation, we observed that B. subtilis root colonization is decreased by the presence of P. fluorescens and P. protegens. To determine if B. subtilis can adapt to the inhibitory effect of Pseudomonas on roots, we conducted adaptative laboratory evolution experiments with B. subtilis in mono-association or co-cultured with P. fluorescens on tomato plant roots. Evolved isolates with various colony morphology and stronger colonization capacity of both tomato plant and A. thaliana roots emerged rapidly from the two evolution experiments. Certain evolved isolates had also a better fitness on root in presence of other Pseudomonas species. Whole genome sequencing revealed that single nucleotide polymorphism (SNPs) in negative biofilm regulator genes ywcC or sinR were found in all independent lineages, suggesting their involvement in enhanced root colonization. These findings provide insights into the molecular mechanisms underlying B. subtilis adaptation to root colonization and highlight the potential of directed evolution to enhance beneficial traits of PGPRs.

microbiology↗

bioRxiv2019

Global state of deworming coverage and inequity in low-income and middle-income countries: a spatiotemporal study of household health surveys

IntroductionMass deworming against soil-transmitted helminthiasis (STH) is a hallmark program in the neglected tropical diseases portfolio that is designed to be equitable and \"pro-poor\". However, the extent to which current deworming treatment programs achieve equitable coverage across wealth class and gender remains unclear, and the current public health metric of national deworming coverage does not include representation of inequity. This study develops a framework to measure both coverage and equity in global deworming to guide future programmatic evaluation, investment, and metric design.\n\nMethodsWe used nationally representative, geospatial household survey data that measured mother-reported deworming receipt in pre-school age children (age 1-4 years) in the previous 6 months. We estimated global deworming coverage disaggregated by geography, wealth quintile and gender and computed an equity index. We examined trends in coverage and equity index across countries, within countries, and over time. We used a regression model to compute the household correlates of deworming receipt and ecological correlates of equitable deworming.\n\nFindingsOur study included 820,883 pre-school age children living in 50 STH-endemic countries between 2004 and 2017. Globally, the mean global deworming coverage in pre-school children was estimated at 36%. The sub-national coverage ranged from 0.5% to 87.5%, and within-country variation was greater than between-country variation in coverage. The equity index was undesirable (deworming was consistently concentrated in the wealthier populations) in every endemic region of 12 countries. Of the 31 study countries that WHO reported achieving the goal of 75% national coverage, 26 had persistent inequity in deworming as defined by the mean equity index. Deworming equity modestly improved over time, and within-country variation in inequity decreased over time. We did not detect differences in deworming equity by gender. We found the strongest household correlates of deworming to be vitamin A supplementation and receipt of three doses of diphtheria-tetanus-pertussis vaccine (DTP3), while the strongest ecological predictors of equitable deworming were regions with higher coverage of health services such as DTP3 and vitamin A supplementation.\n\nInterpretationAlthough mass deworming is considered to be \"pro-poor\", we find substantial inequities by wealth, despite often high reported national coverage. These inequities appear to be geographically heterogeneous, modestly improving over time, and we found no evidence of gender differences in inequity. Future reporting of deworming coverage should consider disaggregation by geography, wealth, and gender with incorporation of an equity index to complement national deworming coverage.\n\nFundingBill and Melinda Gates Foundation, Stanford University Medical Scientist Training Program

epidemiology↗