Biology subjects

Jeffries, D.

Publications and source records attributed to Jeffries, D..

3 recordsLinked to original sources

bioRxiv2024

Rates of evolution differ between cell types identified by single-cell RNAseq in threespine stickleback

Rates of evolutionary change vary by gene. While some broad gene categories are highly conserved with little divergence over time, others undergo continuous selection pressure and are highly divergent. Here, we combine single-cell RNA sequencing (scRNAseq) with evolutionary genomics to understand whether certain cell types exhibit faster evolutionary divergence (using their characteristic genes), than other types of cells. Merging scRNAseq with population genomic data, we show that cell types differ in the rate at which their characteristic genes evolve, as measured by allele frequency divergence among many populations (FST) and between species (dN/dS ratios). Neutrophils, B cells, and fibroblasts exhibit elevated FST at characteristic genes, while eosinophils in the intestine and thrombocytes in the head kidney exhibit lower FST than the average for 1000 random genes. Gene network centrality also differed between immune- and non-immune-associated genes, and closeness centrality was positively related to gene FST. These results highlight the value of merging single cell RNA sequencing technology with evolutionary population genomic data, and reveal that genes which define immune cell types exhibit especially rapid evolution.

evolutionary biology↗

bioRxiv2024

Regional Plasmodium falciparum subpopulations and malaria transmission connectivity in Africa were detected with an enlarged panel of genome-wide microsatellite loci

Unravelling the genetic diversity of Plasmodium falciparum malaria parasite provides critical information on how populations are affected by interventions and the environment, especially the evolution of molecular markers associated with parasite fitness and adaptation to drugs and vaccines. This study expands previous studies based on small sets of microsatellite loci, which often showed limited substructure in African populations of P. falciparum. Combining several short tandem repeat detection algorithms, we genotyped and analysed 2329 polymorphic microsatellite loci from next-generation sequences of 992 low-complexity P. falciparum isolates from 15 sub-Saharan African countries. Based on pairwise relatedness, we identified seven subpopulations and gene flow between the Central and Eastern African populations. The most divergent subpopulation was from Ethiopia, while unexpected unique subpopulations from Gabon and Malawi were resolved. Isolates from the Democratic Republic of Congo shared ancestry with multiple regional populations, suggesting a possible founder population of P. falciparum from the Congo basin, where there was stronger geneflow eastwards to Tanzania, and Kenya. and Malawi. The most differentiated microsatellite loci were those around the P. falciparum dihydropteroate synthase (Pfdhps) gene associated with sulphadoxine resistance. Haplotypes around the Pfdhps gene separated the West, Central, and East Africa parasite populations into distinct clusters, suggesting independent local evolution of Pfdhps-associated sulphadoxine resistance alleles in each African region. Overall, this study presents genome-wide microsatellites as markers for resolving P. falciparum population diversity, structure, and evolution in populations like Africa, where there is high gene flow.

genomics↗

bioRxiv2019

Use of a pandemic H1N1 strain with updated haemagglutinin and neuraminidase results in increased nasopharyngeal shedding and improved immunogenicity to Russian-backbone live attenuated influenza vaccine among children aged 2 - 4 years old: an open label, prospective, observational, phase 4 study in The Gambia.

BackgroundPoor efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in intranasal live attenuated influenza vaccine (LAIV) has been demonstrated in several studies. The reasons for this are unclear, but may be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) LAIV strains. MethodsIn an open-label, prospective, observational, phase 4 study, we evaluated the impact of updating the pH1N1 component in the Russian-backbone trivalent LAIV from Cal09 in 2016-17 (n=118) to an A/Michigan/45/2015-like strain (A/17/New York/15/5364, NY15) in 2017-18 (n=126), on shedding and immunogenicity in Gambian children aged 2-4 years old. The study was nested within a larger randomised controlled trial investigating LAIV-microbiome interactions (ClinicalTrials.gov NCT02972957). FindingsCal09 showed impaired nasopharyngeal shedding compared to H3N2 and influenza B, along with sub-optimal serum antibody and T-cell responses. Following the switch to NY15, a significant increase in pH1N1 shedding was seen, along with improvements in seroconversion and influenza-specific CD4+ T-cell responses. Viral kinetics in vitro mirrored these findings, with NY15 showing greater replicative ability than Cal09 in human nasal epithelial cells. Persistent shedding to day 7 was independently associated with both seroconversion and CD4+ T cell response in multivariable logistic regression. InterpretationOur results suggest that the pH1N1 component switch in LAIV may have overcome problems in prior formulations. LAIV effectiveness against pH1N1 should therefore improve in upcoming influenza seasons. Our data also highlight the importance of evaluating replicative fitness, in addition to antigenicity, when selecting annual LAIV components and design of potentially more effective vaccines. FundingThe Wellcome Trust.

clinical trials↗