Biology subjects

Schmidt, J. M.

Publications and source records attributed to Schmidt, J. M..

12 recordsLinked to original sources

bioRxiv2026

Seasonal fluctuations in fitness result in severe reductions in effective population size

Genetic evidence for fluctuating selection has begun to accumulate for different species over the past few decades, especially for the Drosophila genus where studies have reported hundreds of loci undergoing putatively adaptive oscillations across successive seasons. However, most theoretical and simulation studies of fluctuating selection have relied on abstract or weakly parameterized models, making it difficult to assess their relevance for natural populations. In this study, we simulate multilocus seasonally fluctuating selection under a recently developed model and examine its effect on the variance effective population size (Ne) at a genome-wide scale. By recapitulating genomic, demographic, and evolutionary parameters from natural Drosophila populations in our simulations, we were able to reproduce allele frequency oscillations reported in recent studies and show that these lead to [~]50% genome-wide reductions in Ne. We also demonstrate that Ne reductions are well predicted by the maximum frequency amplitude among all adaptively fluctuating loci, and that the frequency amplitudes are largely determined by the number of adaptively fluctuating loci and the strength of their epistatic interactions. Our results demonstrate that fluctuating selection can substantially reduce effective population size and underscore the importance of temporally variable selection in shaping genome-wide patterns of variation beyond classical models. Article SummaryGenetic studies of fluctuating selection in natural populations have grown steadily over the past decade, with reports suggesting that hundreds of loci undergo adaptive oscillations over seasonal timescales in cosmopolitan Drosophila populations. By simulating seasonally fluctuating selection under a recently developed model and ecological scenarios informed by published studies, the authors show that this mode of selection can reduce effective population size by [~]50%, with the magnitude of the reduction correlated with the locus exhibiting the largest allele frequency fluctuations. These findings highlight fluctuating selection as an important factor shaping genome-wide patterns of genetic variation and effective population size.

evolutionary biology↗

bioRxiv2024

NUDIX Hydrolases Target Specific Inositol Pyrophosphates and Regulate Phosphate and Iron Homeostasis, and the Expression of Defense Genes in Arabidopsis

Inositol pyrophosphates (PP-InsPs) are important signaling molecules that regulate diverse cellular processes in eukaryotes, including energy homeostasis, phosphate (Pi) signaling, and phytohormone perception. Yet, in plants, the enzymes responsible for their turnover remain largely unknown. Using a non-hydrolysable PP-InsP analog in a pull-down approach, we identified a family of Arabidopsis NUDIX hydrolases (NUDTs) that group into two closely related subclades. Through in vitro assays, heterologous expression systems, and higher-order gene-edited mutants, we explored the substrate specificities and physiological roles of these hydrolases. Using a combination of strong anion exchange (SAX)-HPLC, PAGE, and capillary electrophoresis electrospray ionization mass spectrometry (CE-ESI-MS), we found that their PP-InsP pyrophosphatase activity is enantiomer-selective and Mg2+-dependent. Specifically, subclade I NUDTs preferentially hydrolyze 4-InsP7, while subclade II NUDTs target 3-InsP7, with minor activity against other PP-InsPs, including 5-InsP7. In higher-order mutants of subclade II NUDTs, we observed defects in both Pi and iron homeostasis, accompanied by increased levels of 1/3-InsP7 and 5-InsP7, with a markedly larger increase in 1/3-InsP7. Ectopic expression of NUDTs from both subclades induced local Pi starvation responses (PSRs), while RNA-seq analysis comparing wildtype (WT) and subclade II nudt12/13/16 loss-of-function plants indicates additional PSR-independent roles, potentially involving 1/3-InsP7 in the regulation of plant defense. Consistently, nudt12/13/16 mutants displayed enhanced resistance to Pseudomonas syringae infection, indicating a role in bacterial pathogen susceptibility. Expanding beyond subclade II NUDTs, we demonstrated susceptibility of the 3PP-position of PP-InsPs to enzymatic activities unrelated to NUDTs, and found that such activities are conserved across plants and humans. Additionally, we found that NUDT effectors from pathogenic ascomycete fungi exhibit a substrate specificity similar to subclade I NUDTs. Collectively, our findings reveal new roles for NUDTs in PP-InsP signaling, plant nutrient and immune responses, and highlight a cross-kingdom conservation of PP-InsP-metabolizing enzymes.

plant biology↗

bioRxiv2024

Granulysin antimicrobial activity promotes dormancy in Mycobacterium tuberculosis

Human tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains a global public health threat. Granulomas constitute a hallmark of TB pathogenesis that can clear, contain or exacerbate an infection. Containment is exploited by Mtb as a hideout to persist in a dormant, antibiotic-tolerant state only to resuscitate upon immunosuppression. The immune determinants of a granulomatous response driving Mtb persistence remain elusive. We here combined an ex vivo granuloma model with peripheral blood mononuclear cell (PBMC) specimens from TB patients and a high-dimensional mass cytometry (CyTOF) approach to shed light on the immune factors prompting Mtb dormancy. Compared to healthy controls, patient-derived ex vivo granulomas rapidly force Mtb to adopt a dormant-like state; an observation that correlates with the presence of activated innate (-like) cytotoxic lymphocytes. We further demonstrate that Mtb dormancy is induced by direct exposure to granulysin, thereby unravelling an immune escape mechanism to cytotoxic lymphocyte activity.

immunology↗

bioRxiv2024

Local genetic adaptation to habitat in wild chimpanzees

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees. One-Sentence SummaryChimpanzees show evidence of local genetic adaptation to habitat, particularly to pathogens, such as malaria, in forests.

evolutionary biology↗

bioRxiv2022

Genetic adaptations to SIV across chimpanzee populations

Central and eastern chimpanzees are infected with Simian Immunodeficiency Virus (SIV) in the wild, typically without developing acute immunodeficiency. Yet the recent zoonotic transmission of chimpanzee SIV to humans, which were naive to the virus, gave rise to the Human Immunodeficiency Virus (HIV), which causes AIDS and is responsible for one of the deadliest pandemics in human history. Chimpanzees have been infected with SIV for tens of thousands of years and have likely evolved to reduce its pathogenicity, becoming semi-natural hosts that largely tolerate the virus. In support of this view, central and eastern chimpanzees show evidence of positive selection in genes involved in SIV/HIV cell entry and immune response to SIV, respectively. We hypothesise that the population first infected by SIV would have experienced the strongest selective pressure to control the lethal potential of zoonotic SIV, and that population genetics will reveal those first critical adaptations. With that aim we used population genomics to investigate signatures of positive selection in the common ancestor of central-eastern chimpanzees. The genes with signatures of positive selection in the ancestral population are significantly enriched in SIV-related genes, especially those involved in the immune response to SIV and those encoding for host genes that physically interact with SIV/HIV (VIPs). This supports a scenario where SIV first infected the central-eastern ancestor and where this population was under strong pressure to adapt to zoonotic SIV. Interestingly, integrating these genes with candidates of positive selection in the two infected subspecies reveals novel patterns of adaptation to SIV. Specifically, we observe evidence of positive selection in numerous steps of the biological pathway responsible for T-helper cell differentiation, including CD4 and multiple genes that SIV/HIV use to infect and control host cells. This pathway is active only in CD4+ cells which SIV/HIV infects, and it plays a crucial role in shaping the immune response so it can efficiently control the virus. Our results confirm the importance of SIV as a selective factor, identify specific genetic changes that may have allowed our closest living relatives to reduce SIVs pathogenicity, and demonstrate the potential of population genomics to reveal the evolutionary mechanisms used by naive hosts to reduce the pathogenicity of zoonotic pathogens. Author SummaryChimpanzees are at the origin of HIV-1, a virus that generates an incurable disease and that generated a pandemic that has claimed 35 million lives. Chimpanzees have evolved to control the pathogenicity of the virus, which does not typically develop into AIDS in the same way as in humans. Identifying the genetic adaptations responsible for this process provides critical knowledge about SIV and HIV. Our analysis of chimpanzee genetic adaptations identified specific genes and molecular pathways involved in adaptation to SIV, providing important insights into the mechanisms that likely allowed our closest living relatives to control SIV/HIV. Further, we establish SIV as a strong and recurrent selective pressure in central and eastern chimpanzees, two important subspecies of large mammals that are currently endangered.

evolutionary biology↗

bioRxiv2020

Beyond soil health: the trophic effects of cover crops shape predator communities

Maintaining habitat throughout the season in annual cropping systems provides resource stability for arthropod communities. Stabilizing resource availability should lead to diverse predatory communities and their associated ecosystem services such as biological control. There is a need for studies to test change in predator communities due to habitat provisioning and estimate associated food web responses. Here we quantified predator community structure and used molecular gut-content analysis to reconstruct predator food webs in response to winter cover crops (i.e. cereal and legume based) in a cotton agroecosystem. Predators were collected from experimental field plots during each major crop development stage in 2017 and 2018, and PCR was used to estimate predator roles and responses to cover crop treatments. Cotton planted into a rye cover crop residue promoted unique predator communities in the early and mid-season as compared to no-cover fields. Correspondingly, we observed dissimilar prey consumption among cover crop treatments. While predators consumed incidental pests at high frequencies (e.g. aphids), predation on key pests by natural enemies in this system was lacking. The use of winter cover crops and reduced tillage practices increased the consumption of alternative prey by natural enemies on seedling cotton, encouraging high predator diversity that aligns temporally with potential early season pest outbreaks. Therefore, cover crops should be further integrated into integrated pest management strategies.

ecology↗

bioRxiv2019

Evidence that viruses, particularly SIV, drove genetic adaptation in natural populations of eastern chimpanzees

All four subspecies of chimpanzees are endangered. Differing in their demographic histories and geographical ranges within sub-Saharan Africa, they have likely adapted to different environmental factors. We show that highly differentiated SNPs in eastern chimpanzees are uniquely enriched in genic sites in a way that is expected under recent adaptation. These sites are enriched for genes that differentiate the immune response to infection by simian immunodeficiency virus (SIV) in natural vs. non-natural host species. Conversely, central chimpanzees exhibit selective sweeps at the cytokine receptors CCR3, CCR9 and CXCR6 - paralogs of CCR5 and CXCR4, the two major receptors utilized by HIV to enter human cells. Thus, we infer that SIV may be eliciting distinctive adaptive responses in different chimpanzee subspecies. Since central chimpanzee SIV is the source of the global HIV/AIDS pandemic, understanding the mechanisms that limit pathogenicity of SIV in chimpanzees can broaden our understanding of HIV infection in humans.

evolutionary biology↗

bioRxiv2018

Structural variants and selective sweep foci contribute to insecticide resistance in the Drosophila melanogaster genetic reference panel

Patterns of nucleotide polymorphism within populations of Drosophila melanogaster suggest that insecticides have been the selective agents driving the strongest recent bouts of positive selection. However, there is a need to explicitly link selective sweep loci to the particular insecticide phenotypes that could plausibly account for the drastic selective responses that are observed in these non-target insects. Here, we screen the Drosophila Genetic Reference Panel with two common insecticides; malathion (an organophosphate) and permethrin (a pyrethroid). Genome wide association studies map survival-on-malathion to two of the largest sweeps in the D. melanogaster genome; Ace and Cyp6g1. Malathion survivorship also correlates with lines which have high levels of Cyp12d1 and Jheh1 and Jheh2 transcript abundance. Permethrin phenotypes map to the largest cluster of P450 genes in the Drosophila genome, however in contrast to a selective sweep driven by insecticide use, the derived state seems to be associated with susceptibility. These results underscore previous findings that highlight the importance of structural variation to insecticide phenotypes: Cyp6g1 exhibits copy number variation and transposable element insertions, Cyp12d1 is tandemly duplicated, the Jheh loci are associated with a Bari1 transposable element insertion, and a Cyp6a17 deletion is associated with susceptibility.

genetics↗

bioRxiv2018

Human local adaptation of the TRPM8 cold receptor along a latitudinal cline

Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on this question, we exploit the fact that humans are a cosmopolitan species that inhabits territories under a wide range of temperatures. Focusing on cold perception - which is central to thermoregulation and survival in cold environments-- we show evidence of recent local adaptation on TRPM8. This gene encodes for a cation channel that is, to date, the only temperature receptor known to mediate an endogenous response to moderate cold. The upstream variant rs10166942 shows extreme population differentiation, with frequencies that range from 5% in Nigeria to 88% in Finland (placing this SNP in the 0.02% tail of the FST empirical distribution). When all populations are jointly analysed, allele frequencies correlate with latitude and temperature beyond what can be explained by shared ancestry and population substructure. Using a Bayesian approach, we infer that the allele originated and evolved neutrally in Africa, while positive selection raised its frequency to different degrees in Eurasian populations, resulting in allele frequencies that follow a latitudinal cline. We infer strong positive selection, in agreement with ancient DNA showing high frequency of the allele in Europe 3,000 to 8,000 years ago. rs10166942 is important phenotypically because its ancestral allele is protective of migraine. This debilitating disorder varies in prevalence across human populations, with highest prevalence in individuals of European descent -precisely the population with the highest frequency of rs10166942 derived allele. We thus hypothesize that local adaptation on previously neutral standing variation may have contributed to the genetic differences that exist in the prevalence of migraine among human populations today.\n\nAuthor SummarySome human populations were likely under strong pressure to adapt biologically to cold climates during their colonization of non-African territories in the last 50,000 years. Such putative adaptations required genetic variation in genes that could mediate adaptive responses to cold. TRPM8 is potentially one such gene, being the only known receptor for the sensation of moderate cold temperature. We show that a likely regulatory genetic variant nearby TRPM8 has several signatures of positive selection rising its frequency in Eurasian populations during the last 25,000 years. While the genetic variant was and is rare in Africa, it is now common outside of Africa, with frequencies that strongly correlate with latitude and are highest in northern European populations. Interestingly, this same genetic variant has previously been strongly associated with migraine. This suggests that adaptation to cold has potentially contributed to the variation in migraine prevalence that exists among human groups today.

genetics↗

bioRxiv2017

Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus of each cell. There are currently two distinct views of genome organization that are derived from different technologies. The first view, derived from genome-wide proximity ligation methods (e.g. Hi-C), suggests that genome organization is largely organized around chromosomes. The second view, derived from in situ imaging, suggests a central role for nuclear bodies. Yet, because microscopy and proximity-ligation methods measure different aspects of genome organization, these two views remain poorly reconciled and our overall understanding of how genomic DNA is organized within the nucleus remains incomplete. Here, we develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which moves away from proximity-ligation and enables genome-wide detection of higher-order DNA interactions within the nucleus. Using SPRITE, we recapitulate known genome structures identified by Hi-C and show that the contact frequencies measured by SPRITE strongly correlate with the 3-dimensional distances measured by microscopy. In addition to known structures, SPRITE identifies two major hubs of inter-chromosomal interactions that are spatially arranged around the nucleolus and nuclear speckles, respectively. We find that the majority of genomic regions exhibit preferential spatial association relative to one of these nuclear bodies, with regions that are highly transcribed by RNA Polymerase II organizing around nuclear speckles and transcriptionally inactive and centromere-proximal regions organizing around the nucleolus. Together, our results reconcile the two distinct pictures of nuclear structure and demonstrate that nuclear bodies act as inter-chromosomal hubs that shape the overall 3-dimensional packaging of genomic DNA in the nucleus.

genomics↗

bioRxiv2017

Percentage-Based Author Contribution Index. A Universal Measure Of Author Contribution To Scientific Articles

Deciphering the amount of work provided by different co-authors of a scientific paper has been a recurrent problem in science. Despite the myriad of metrics available, the scientific community still largely relies on the position in the list of authors to evaluate contributions, a metric that attributes subjective and unfounded credit to co-authors. We propose an easy to apply, fair and universally comparable metric to measure and report co-authors contribution in the scientific literature. The proposed Author Contribution Index (ACI) is based on contribution percentages provided by the authors, preferably at the time of submission. Researchers can use ACI for a number of purposes, including comparing the contributions of different authors, describing the contribution profile of a researcher or analysing how contribution changes through time. We provide an example analysis based on data collected from 97 scientists from the field of ecology who voluntarily responded to an online anonymous survey.

scientific communication and education↗

bioRxiv2016

Extracellular peptidases in subsurface sediments of the White Oak River estuary, NC, suggest microbial community adaptation to oxidize degraded organic matter

Anoxic subsurface sediments contain communities of heterotrophic microorganisms that metabolize organic carbon at extraordinarily slow rates. In order to assess the mechanisms by which subsurface microorganisms access detrital sedimentary organic matter, we measured kinetics of a range of extracellular peptidases in anoxic sediments of the White Oak River estuary, NC. Nine distinct peptidase substrates were enzymatically hydrolyzed at all depths. Potential peptidase activities (Vmax) decreased with increasing sediment depth, although Vmax expressed on a per cell basis was approximately the same at all depths. Half-saturation constants (Km) decreased with depth, indicating peptidases that functioned more efficiently at low substrate concentrations. Potential activities of extracellular peptidases acting on molecules that are enriched in degraded organic matter (D-phenylalanine and L-ornithine) increased relative to enzymes that act on L-phenylalanine, further suggesting microbial community adaptation to access degraded organic matter. Nineteen classes of predicted, exported peptidases were identified in genomic data from the same site, of which genes for class C25 (gingipain-like) peptidases represented more than 40% at each depth. Methionine aminopeptidases, zinc carboxypeptidases, and class S24-like peptidases, which are involved in single-stranded DNA repair, were also abundant. These results suggest a subsurface heterotrophic microbial community that primarily accesses low-quality detrital organic matter via a diverse suite of well-adapted extracellular enzymes.\n\nIO_SCPLOWMPORTANCEC_SCPLOWBurial of organic carbon in marine and estuarine sediments represents a long-term sink for atmospheric carbon dioxide. Globally, [~]40% of organic carbon burial occurs in anoxic estuaries and deltaic systems. However, the ultimate controls on the amount of organic matter that is buried in sediments, versus oxidized into CO2, are poorly constrained. Here we used a combination of enzyme assays and metagenomic analysis to identify how subsurface microbial communities catalyze the first step of proteinaceous organic carbon degradation. Our results show that microbial communities in deeper sediments are adapted to access molecules characteristic of degraded organic matter, suggesting that those heterotrophs are adapted to life in the subsurface.

ecology↗