Biology subjects

Tedder, A.

Publications and source records attributed to Tedder, A..

5 recordsLinked to original sources

bioRxiv2024

Identifying ancient antibiotic resistance genes in archaeological dental calculus

Research on ancient antimicrobial resistance is limited, and appropriate screening criteria for identifying antibiotic (ARGs) and metal resistance genes (MRGs) in archaeological samples are unclear. We assessed the impact of DNA damage and contamination on ARG and MRG detection in ancient metagenomic sequences. Starting from a set of modern oral metagenomic samples, we simulated diagenetic DNA damage as expected in ancient oral metagenomic samples. Then we estimated the impact of this damage on ARG and MRG prediction at different identity thresholds. We also examined 25 post-industrial (ca. 1850 - 1901) dental calculus samples before and after decontamination to study the rates of false positive (FP) and negative (FN) ARG and MRG predictions introduced by sample contamination. The tests showed that diagenetic damage does not significantly affect resistance gene detection, but contamination does. Furthermore, while high thresholds are advisable when feasible, overall identity thresholds do not significantly affect the rates of FPs and FNs. Additionally, comparing post-industrial and modern dental calculus revealed Tetracycline ARGs as dominant in both contaminated ancient samples and modern samples, and MLS (Macrolide, Lincosamide, and Streptogramins) ARGs as prevalent in historical samples before widespread antibiotic use. Data summaryThe simulated data were generated from 182 human oral biofilm samples, retrieved from the European Nucleotide Archive (ENA project: PRJNA817430) (Anderson et al., 2023). Additionally, real ancient (PRJEB1716 and PRJEB12831) and modern (PRJEB1716) metagenomic sequences were selected from metagenomic datasets published by Standeven et al. (2024). Impact statementAntimicrobial resistance (AMR) is a global health crisis. Studying the adaptability of microorganisms over centuries allows us to understand key factors that contribute to the survival and spread of antibiotic-resistant bacteria today. We know that antibiotic abuse is a key driver of AMR; however, further study into specific environmental niches that promote the evolution of antibiotic-resistant bacteria is important. For example, the extent to which the oral microbiome facilitates the increase of certain antibiotic-resistant genes and the impact of metal pollution on the spread of AMR. To investigate these key areas, it is essential to examine oral microbiomes across time, providing a complete perspective on the evolution of AMR. However, ancient metagenomics poses problems for the screening of antibiotic and metal-resistant genes in ancient bacterial DNA due to nucleotide base damage and short-read data. Through thorough threshold experimentation to establish optimal screening criteria for ancient resistance gene identification, and by addressing gaps in knowledge of ancient resistance genes, this research offers clinical significance to existing research and contributes to the development of strategies aimed at easing the impact of AMR on public health.

microbiology↗

bioRxiv2024

An efficient pipeline for creating metagenomic-assembled genomes from ancient oral microbiomes

Metagenomic-assembled genomes (MAGs) are difficult to recover from ancient DNA (aDNA) due to substantial fragmentation, degradation, and multi-source contamination. These complexities associated with aDNA raise concerns about whether bioinformatic tools intended for interpreting modern DNA are suitable for reconstructing ancient MAGs. Using simulated modern and ancient data, we investigated: 1) how using binning tools designed for modern DNA affects our ability to effectively construct MAGs from ancient genomes; 2) the performance of three different binning tools for aDNA samples; and 3) whether a one size fits all approach is suitable for ancient metagenomics. We established that binning tools for modern DNA performed efficiently on simulated modern and ancient DNA. When applied to real archaeological DNA spanning 5000 years, we retrieve high-confidence MAGs in most cases.

microbiology↗

bioRxiv2024

An extensive archaeological dental calculus dataset spanning 5000 years for ancient human oral microbiome research

Archaeological dental calculus can provide detailed insights into the ancient human oral microbiome. We offer a multi-period, multi-site, ancient shotgun metagenomic dataset consisting of 174 samples obtained primarily from archaeological dental calculus derived from various skeletal collections in the United Kingdom. This article describes all the materials used including the skeletons historical period and burial location, biological sex, and age determination, data accessibility, and additional details associated with environmental and laboratory controls. In addition, this article describes the laboratory and bioinformatic methods associated with the dataset development and discusses the technical validity of the data following quality assessments, damage evaluations, and decontamination procedures. Our approach to collecting, making accessible, and evaluating bioarchaeological metadata in advance of metagenomic analysis aims to further enable the exploration of archaeological science topics such as diet, disease, and antimicrobial resistance (AMR).

microbiology↗

bioRxiv2018

Genetic basis and timing of a major mating system shift in Capsella

Shifts from outcrossing to self-fertilisation have occurred repeatedly in many different lineages of flowering plants, and often involve the breakdown of genetic outcrossing mechanisms. In the Brassicaceae, self-incompatibility (SI) allows plants to ensure outcrossing by recognition and rejection of self-pollen on the stigma. This occurs through the interaction of female and male specificity components, consisting of a pistil based receptor and a pollen-coat protein, both of which are encoded by tightly linked genes at the S-locus. When benefits of selfing are higher than costs of inbreeding, theory predicts that loss-of-function mutations in the male (pollen) SI component should be favoured, especially if they are dominant. However, it remains unclear whether mutations in the male component of SI are predominantly responsible for shifts to self-compatibility, and testing this prediction has been difficult due to the challenges of sequencing the highly polymorphic and repetitive ~100 kbp S-locus. The crucifer genus Capsella offers an excellent opportunity to study multiple transitions from outcrossing to self-fertilization, but so far, little is known about the genetic basis and timing of loss of SI in the self-fertilizing diploid Capsella orientalis. Here, we show that loss of SI in C. orientalis occurred within the past 2.6 Mya and maps as a dominant trait to the S-locus. Using targeted long-read sequencing of multiple complete S-haplotypes, we identify a frameshift deletion in the male specificity gene SCR that is fixed in C. orientalis, and we confirm loss of male SI specificity. We further analyze RNA sequencing data to identify a conserved, S-linked small RNA (sRNA) that is predicted to cause dominance of self-compatibility. Our results suggest that degeneration of pollen SI specificity in dominant S-alleles is important for shifts to self-fertilization in the Brassicaceae.\n\nAuthor SummaryAlready Darwin was fascinated by the widely varying modes of plant reproduction. The shift from outcrossing to self-fertilization is considered one of the most frequent evolutionary transitions in flowering plants, yet we still know little about the genetic basis of these shifts. In the Brassicaceae, outcrossing is enforced by a self-incompatibility (SI) system that enables the recognition and rejection of self pollen. This occurs through the action of two tightly linked genes at the S-locus, that encode a receptor protein located on the stigma (female component) and a pollen ligand protein (male component), respectively. Nevertheless, SI has frequently been lost, and theory predicts that mutations in the male component should have an advantage during the loss of SI, especially if they are dominant. To test this hypothesis, we mapped the loss of SI in a selfing species from the genus Capsella, a model system for evolutionary genomics. We found that loss of SI mapped to the S-locus, which harbored a dominant loss-of-function mutation in the male SI protein, and as expected, we found that male specificity was indeed lost in C. orientalis. Our results suggest that transitions to selfing often involve parallel genetic changes.

evolutionary biology↗

bioRxiv2017

Demography And Mating System Shape The Genome-Wide Impact Of Purifying Selection In Arabis alpina

Plant mating systems have profound effects on levels and structuring of genetic variation, and can affect the impact of natural selection. While theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study the effect of mating system on purifying selection by conducting population genomic analyses on whole-genome resequencing data from 38 European individuals of the arctic-alpine crucifer Arabis alpina. We find that outcrossing and mixed-mating populations maintain genetic diversity at similar levels, whereas highly self-fertilizing Scandinavian A. alpina show a strong reduction in genetic diversity, most likely as a result of a postglacial colonization bottleneck. We further find evidence for accumulation of genetic load in highly self-fertilizing populations, whereas the genome-wide impact of purifying selection does not differ greatly between mixed-mating and outcrossing populations. Our results demonstrate that intermediate levels of outcrossing may allow efficient selection against harmful alleles whereas demographic effects can be important for relaxed purifying selection in highly selfing populations. Thus, both mating system and demography shape the impact of purifying selection on genomic variation in A. alpina. These results are important for an improved understanding of the evolutionary consequences of mating system variation and the maintenance of mixed-mating strategies.\n\nSignificanceIntermediate outcrossing rates are theoretically predicted to maintain effective selection against harmful alleles, but few studies have empirically tested this prediction using genomic data. We used whole-genome resequencing data from alpine rock-cress to study how genetic variation and purifying selection vary with mating system. We find that populations with intermediate outcrossing rates have similar levels of genetic diversity as outcrossing populations, and that purifying selection against harmful alleles is efficient in mixed-mating populations. In contrast, self-fertilizing populations from Scandinavia have strongly reduced genetic diversity, and accumulate harmful mutations, likely as a result of demographic effects of postglacial colonization. Our results suggest that mixed-mating populations can avoid the negative evolutionary consequences of high self-fertilization rates.

evolutionary biology↗