Biology subjects

Haile, A.

Publications and source records attributed to Haile, A..

7 recordsLinked to original sources

bioRxiv2026

Genomic history and ecology of local adaptation in sky-island Arabidopsis thaliana

Adaptation to local environments in isolated habitats may produce independent solutions to similar ecological challenges, yielding insight into the predictability of evolution. Alpine plants on tropical sky-islands, in particular, must cope with extreme diurnal fluctuations in temperature and radiation. These populations may undergo parallel local adaptation to high elevation, or alternatively, distinct local adaptations due to intermountain heterogeneity. For instance, abiotic stress on mountain peaks could select for stress tolerance or stress escape/bet-hedging strategies. We tested these hypotheses in experiments with 163 newly sequenced Arabidopsis thaliana genotypes from East Africa. Genomic history followed geography: Ugandan genotypes were the most divergent, and Ethiopian genotypes more closely related. Effective population size decreased towards the present on all mountains, in concert with declining climatic suitability since the end of the African Humid Period. Genotypes from the colder and seasonally drier mountains showed strong seed dormancy, rapid flowering, short/curved inflorescences. In contrast, genotypes from the milder and less seasonal mountains showed less seed dormancy, delayed flowering, and long/erect inflorescences. Elevational clines found in multiple mountains included seed dormancy-release with short (vs. long) stratification, and shorter inflorescences, at higher elevations. In a genome-wide association study (GWAS) with inflorescence length, we detected the TCP5 transcription factor, but these variants only segregated in some mountains and showed an elevational allele frequency cline at only one mountain. Allele reuse based on GWAS was greater between Ethiopian populations (QTL allele-frequency r > 0.9 for most traits), and generally lower between Uganda and the rest. Results indicate limited evidence of parallel local adaptation along elevation, suggesting that dwarf inflorescences are selected for in multiple mountain tops, while bet-hedging prevails in cold and seasonally dry sky-islands, and divergent selection along elevation in other traits can evolve in mountains with milder climates. Overall these results suggest a long history of isolation and ecological complexity limit the predictability of local adaptation.

evolutionary biology↗

bioRxiv2025

Museum genomics reveals temporal genetic stasis and global genetic diversity in Arabidopsis thaliana

Global patterns of population genetic variation through time offer a window into evolutionary processes that maintain diversity. Over time, lineages may expand or contract their distribution, causing turnover in population genetic composition. At individual loci, migration, drift, and selection (among other processes) may affect allele frequencies. Museum specimens of widely distributed species offer a unique window into the genetics of understudied populations and changes over time. Here, we sequenced genomes of 130 herbarium specimens and 91 new field collections of Arabidopsis thaliana and combined these with published genomes. We sought a broader view of genomic diversity across the species, and to test if population genomic composition is changing through time. We documented extensive and previously uncharacterized diversity in a range of populations in Africa, populations that are under threat from anthropogenic climate change. Through time, we did not find dramatic changes in genomic composition of populations. Instead, we found a pattern of genetic change every 100 years of the same magnitude seen when comparing Eurasian populations that are 185 km apart, potentially due to a combination of drift and changing selection. We found only mixed signals of polygenic adaptation at phenology and physiology QTL. We did find that genes conserved across eudicots show altered levels of directional allele frequency change, potentially due to variable purifying and background selection. Our study highlights how museum specimens can reveal new dimensions of population diversity and show how wild populations are evolving in recent history.

evolutionary biology↗

bioRxiv2023

Spatiotemporal development of the human T follicular helper cell response to Influenza vaccination

We profiled blood and draining lymph node (LN) samples from human volunteers after influenza vaccination over two years to define evolution in the T follicular helper cell (TFH) response. We show LN TFH cells expanded in a clonal-manner during the first two weeks after vaccination and persisted within the LN for up to six months. LN and circulating TFH (cTFH) clonotypes overlapped but had distinct kinetics. LN TFH cell phenotypes were heterogeneous and mutable, first differentiating into pre-TFH during the month after vaccination before maturing into GC and IL-10+ TFH cells. TFH expansion, upregulation of glucose metabolism, and redifferentiation into GC TFH cells occurred with faster kinetics after re-vaccination in the second year. We identified several influenza-specific TFH clonal lineages, including multiple responses targeting internal influenza proteins, and show each TFH state is attainable within a lineage. This study demonstrates that human TFH cells form a durable and dynamic multi-tissue network.

immunology↗

bioRxiv2022

The genomics and physiology of abiotic stressors associated with global elevation gradients in Arabidopsis thaliana

Phenotypic and genetic diversity in Arabidopsis thaliana may be associated with adaptation along its wide elevational range. We took a multi-regional view of elevational adaptation and in a diverse panel of ecotypes measured plant responses to high elevation stressors: low partial CO2 pressure, high light, and night freezing. We conducted genome-wide association studies (GWAS) and found evidence of contrasting locally adaptive clines between regions. Western Mediterranean ecotypes showed low {delta}13C/early flowering at low elevations to high {delta}13C/late flowering at high elevations, while Asian ecotypes showed the opposite pattern. We mapped different candidate genes for each region, and trait-associated SNPs often showed elevational clines likely maintained by selection. Antioxidants and pigmentation showed regional differentiation but rarely elevational clines. GWAS for antioxidants identified an ascorbate transporter PHT4;4 (AT4G00370), which we show alters non-photochemical quenching kinetics under high light and may be involved in local adaptation to Moroccan mountains. The low-antioxidant PHT4;4 GWAS allele was associated with lower PHT4;4 expression and this haplotype was characterized by binding sites of a transcription factor family, DOF, involved in light response. Our results highlight how physiological and genomic elevational clines in different regions can be unique, underlining the complexity of local adaptation in widely distributed species.

evolutionary biology↗

bioRxiv2021

Germinal centre-driven maturation of B cell response to SARS-CoV-2 vaccination

Germinal centres (GC) are lymphoid structures where vaccine-responding B cells acquire affinity-enhancing somatic hypermutations (SHM), with surviving clones differentiating into memory B cells (MBCs) and long-lived bone marrow plasma cells (BMPCs)1-4. Induction of the latter is a hallmark of durable immunity after vaccination5. SARS-CoV-2 mRNA vaccination induces a robust GC response in humans6-8, but the maturation dynamics of GC B cells and propagation of their progeny throughout the B cell diaspora have not been elucidated. Here we show that anti-SARS-CoV-2 spike (S)-binding GC B cells were detectable in draining lymph nodes for at least six months in 10 out of 15 individuals who had received two doses of BNT162b2, a SARS-CoV-2 mRNA vaccine. Six months after vaccination, circulating S-binding MBCs were detected in all participants (n=42) and S-specific IgG-secreting BMPCs were detected in 9 out of 11 participants. Using a combined approach of single-cell RNA sequencing of responding blood and lymph node B cells from eight participants and expression of the corresponding monoclonal antibodies, we tracked the evolution of 1540 S-specific B cell clones. SHM accumulated along the B cell differentiation trajectory, with early blood plasmablasts showing the lowest frequencies, followed by MBCs and lymph node plasma cells whose SHM largely overlapped with GC B cells. By three months after vaccination, the frequency of SHM within GC B cells had doubled. Strikingly, S+ BMPCs detected six months after vaccination accumulated the highest level of SHM, corresponding with significantly enhanced anti-S polyclonal antibody avidity in blood at that time point. This study documents the induction of affinity-matured BMPCs after two doses of SARS-CoV-2 mRNA vaccination in humans, providing a foundation for the sustained high efficacy observed with these vaccines.

immunology↗

bioRxiv2021

SARS-CoV-2 mRNA vaccination elicits robust and persistent T follicular helper cell response in humans

SARS-CoV-2 mRNA vaccines induce robust anti-spike (S) antibody and CD4+ T cell responses. It is not yet clear whether vaccine-induced follicular helper CD4+ T (TFH) cell responses contribute to this outstanding immunogenicity. Using fine needle aspiration of draining axillary lymph nodes from individuals who received the BNT162b2 mRNA vaccine, we show that frequency of TFH correlates with that of S-binding germinal center B cells. Mining of the responding TFH T cell receptor repertoire revealed a strikingly immunodominant HLADPB1* 04-restricted response to S167-180 in individuals with this allele, which is among the most common HLA alleles in humans. Paired blood and lymph node specimens show that while circulating S-specific TFH cells peak one week after the second immunization, S-specific TFH persist at nearly constant frequencies for at least six months. Collectively, our results underscore the key role that robust TFH cell responses play in establishing long-term immunity by this efficacious human vaccine.

immunology↗

bioRxiv2020

Molecular classification of the placebo effect in nausea

Numerous studies have shown that the mere expectation improvement can alleviate symptoms in various conditions. These placebo effects often include reliable changes in central and peripheral organ systems. Here, we tested for the first time whether placebo effects can be monitored and predicted by plasma proteins. In a randomized controlled design, 90 healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to placebo treatment or no treatment on the second day. Significant placebo effects on nausea, motion sickness, and gastric activity could be verified. Using state-of-the-art proteomics, 74 differentially regulated proteins were identified in placebo-treated participants as compared to no-treatment controls. Gene ontology (GO) enrichment analyses of these proteins revealed acute-phase proteins as well as microinflammatory proteins to be reliable plasma correlates of the placebo effect. Regression analyses showed that day-adjusted scores of nausea indices in the placebo group were predictable by the identified GO protein signatures. We next identified specific plasma proteins, for which a significant amount of variance could be explained by the experimental factors sex, group, nausea, or their interactions. GO enrichment analyses of these proteins identified grooming behavior as a prominent hit, based on neurexin-1 (NRXN1) and contactin-associated protein-like 4 (CNTNAP4). Finally, Receiver Operator Characteristics (ROC) allowed to identify specific plasma proteins differentiating placebo responders from non-responders. These comprised immunoglobulins (IGHM, IGKV1D-16, IGHV3-23, IGHG1) and MASP2, related to regulation of complement activation, as well as proteins involved in oxidation reduction processes (QSOX1, CP TXN). This proof-of-concept study indicates that plasma proteomics are a promising tool to identify molecular correlates and predictors of the placebo effect in humans.

neuroscience↗