Biology subjects

Etherington, G. J.

Publications and source records attributed to Etherington, G. J..

11 recordsLinked to original sources

bioRxiv2025

High-quality genome assembly for the genetically improved Abbassa Nile tilapia enables the reconstruction of X and Y haplotypes

The success of the Nile tilapia (Oreochromis niloticus) as an aquaculture species is partly the result of continuous selective breeding leading to high performing strains. These elite strains have been derived from breeding populations of diverse origins and crosses with other Oreochromis species. Owing to the complex and unique evolutionary histories of each strain, existing reference genomes of wild populations are unsuitable to implement genomic selection for beneficial traits such as growth or environmental resilience in aquaculture programmes. Here we generated a high-quality genome assembly and annotation of the WorldFish Genetically Improved Abbassa Nile tilapia (GIANT) elite strain using a combination of PacBio HiFi, and Omni-C Illumina sequencing. As a male Abbassa Nile tilapia was used for the generation of the genome assembly, we reconstructed both X and Y haplotypes, identifying both amhY and amh{Delta}y on LG23 indicating that Abbassa likely shares the same sex determination system as GIFT, and thereby differs from the existing reference genome, whose sex determination loci are located on LG1.

genomics↗

bioRxiv2024

Characterisation of the historic demographic decline of the British European polecat population

The European polecat (Mustela putorius) has a widespread distribution across many countries of mainland Europe but is documented to be declining within these ranges. In Britain, direct persecution led to a severe decline of the polecat population during the 19th century. Unlike European mainland populations, it is now recovering across much of its former British range. The genomic and conservation implications of such a severe demographic decline, followed by the current recovery, have still to be characterised in the European polecat in Britain. Here we carry out population-level whole-genome analyses of 65 polecats from Britain (Wales and England) and the European mainland. Our analyses reveal that Welsh polecats show genetic variability from both English and European polecats, while British polecats as a whole exhibit signs of genetic isolation from mainland European populations. We also reconstructed the demographic history of the Welsh polecat to quantify the magnitude of the bottleneck. Our analyses confirmed the drastic decline of the Welsh polecats effective population size, with a severe genetic bottleneck around 30-40 generations ago (1854-1894). We investigated whether whole genome diversity reflected this demographic event and found that Welsh polecats had significantly less genetic diversity than English polecats, but not European polecats. Runs of homozygosity and genetic load present in Welsh and English polecat genomes also indicated recent historic inbreeding. Our findings suggest that the increase in the British polecat population size may be attributed to admixture events. Additionally, we demonstrate that the Welsh polecat constitutes a genetically distinct population, which could be crucial for the overall conservation of European polecats by preserving unique genetic diversity.

evolutionary biology↗

bioRxiv2023

Schizosaccharomyces versatilis represents a distinct evolutionary lineage.

The fission yeast species Schizosaccharomyces japonicus is currently divided into two varieties - S. japonicus var. japonicus and S. japonicus var. versatilis. Here we examine the var. versatilis isolate CBS5679. The CBS5679 genome shows 88% coding sequence identity to the reference genome of S. japonicus var. japonicus at the coding sequence level, with phylogenetic analyses suggesting that it has split from the S. japonicus lineage 25 million years ago. The CBS5679 genome contains a reciprocal translocation between chromosomes 1 and 2, together with several large inversions. The products of genes linked to the major translocation are associated with "metabolism" and "cellular assembly" ontology terms. We further show that CBS5679 does not generate viable progeny with the reference strain of S. japonicus. Although CBS5679 shares closer similarity to the "type" strain of var. versatilis as compared to S. japonicus, it is not identical to the type strain, suggesting population structure within var. versatilis. We recommend that the taxonomic status of S. japonicus var. versatilis is raised, with it being treated as a separate species, Schizosaccharomyces versatilis. Take-awayO_LIThe taxonomic status of Schizosaccharomyces versatilis is addressed. C_LIO_LIS. versatilis diverged from S. japonicus around 25 million years ago. C_LIO_LIS. versatilis does not produce viable progeny in crosses with S. japonicus. C_LIO_LIS. versatilis has a reciprocal translocation between chromosomes 1 and 2. C_LIO_LIThe Gene Ontology terms for genes in the translocations are enriched for terms connected to "metabolism" and "cellular assembly". C_LI

evolutionary biology↗

bioRxiv2023

Telomere-to-telomere Schizosaccharomyces japonicus genome assembly reveals hitherto unknown genome features

Schizosaccharomyces japonicus belongs to the single-genus class Schizosaccharomycetes, otherwise known as fission yeasts. As part of a composite model system with its widely studied S. pombe sister species, S. japonicus has provided critical insights into the workings and the evolution of cell biological mechanisms. Furthermore, its divergent biology makes S. japonicus a valuable model organism in its own right. However, the currently available short-read genome assembly contains gaps and has been unable to resolve centromeres and other repeat-rich chromosomal regions. Here we present a telomere-to-telomere long-read genome assembly of the S japonicus genome. This includes the three megabase-length chromosomes, with centromeres hundreds of kilobases long, rich in 5S ribosomal RNAs, transfer RNAs, long terminal repeats, and short repeats. We identify a gene-sparse region on chromosome 2 that resembles a 331 kb centromeric duplication. We revise the genome size of S. japonicus to at least 16.6 Mb and possibly up to 18.12 Mb, at least 30% larger than previous estimates. Our whole genome assembly will support the growing S. japonicus research community and facilitate research in new directions, including centromere and DNA repeat evolution, and yeast comparative genomics. Take-awayO_LIA telomere-to-telomere genome assembly of the fission yeast S. japonicus C_LIO_LIChromosome 2 harbours a previously unknown second centromere-like region C_LIO_LIThe estimated genome size of S. japonicus may be up to 18.12 Mb C_LI

genomics↗

bioRxiv2022

Chromosome-level genome sequence of the Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) highlights regions of introgression with O. mossambicus

BackgroundThe Nile tilapia (Oreochromis niloticus) is the third most important freshwater fish for aquaculture. Its success is directly linked to continuous breeding efforts focusing on production traits such as growth rate and weight. Among those elite strains, the Genetically Improved Farmed Tilapia (GIFT) programme initiated by WorldFish is now distributed worldwide. To accelerate the development of the GIFT strain through genomic selection, a high-quality reference genome is necessary. FindingsUsing a combination of short (10X Genomics) and long read (PacBio HiFi, PacBio CLR) sequencing and a genetic map for the GIFT strain, we generated a chromosome level genome assembly for the GIFT. Using genomes of two closely related species (O. mossambicus, O. aureus), we characterised the extent of introgression between these species and O. niloticus that has occurred during the breeding process. Over 11Mb of O. mossambicus genomic material could be identified within the GIFT genome, including genes associated with immunity but also with traits of interest such as growth rate. ConclusionBecause of the breeding history of elite strains, current reference genomes might not be the most suitable to support further studies into the GIFT strain. We generated a chromosome level assembly of the GIFT strain, characterising its mixed origins, and the potential contributions of introgressed regions to selected traits.

genomics↗

bioRxiv2021

Extensive genome introgression between domestic ferret and European polecat during population recovery in Great Britain.

The European polecat (Mustela putorius) is a mammalian predator which occurs across much of Europe east to the Ural Mountains. In Great Britain, following years of persecution the European polecat has recently undergone a population increase due to legal protection and its range now overlaps that of feral domestic ferrets (Mustela putorius furo). During this range expansion, European polecats hybridised with feral domestic ferrets producing viable offspring. Here we carry out population-level whole genome sequencing on domestic ferrets, British European polecats, and European polecats from the European mainland and find high degrees of genome introgression in British polecats outside their previous stronghold, even in those individuals phenotyped as pure polecats. We quantify this introgression and find introgressed genes under selection that may assist in cognitive function and sight.

evolutionary biology↗

bioRxiv2021

Single Nucleotide Polymorphisms in the Bovine TLR2 Extracellular Domain Contribute to Breed and Species-Specific Innate Immune Functionality

Recent evidence suggests that several cattle breeds may be more resistant to infection with the zoonotic pathogen Mycobacterium bovis than others. Our data presented here suggests that the response to mycobacterial antigens varies in macrophages generated from Brown Swiss (BS) and Holstein Frisian (HF) cattle, two breeds belonging to the Bos taurus family. Whole genome sequencing of the Brown Swiss genome identified several potential candidate genes, in particular Toll-like Receptor-2 (TLR2) a pattern recognition receptor (PRR) that has previously been described to be involved in mycobacterial recognition. Further investigation revealed single nucleotide polymorphisms (SNP) in TLR2 that were identified between DNA isolated from cells of BS and HF cows. Interestingly, one specific SNP, H326Q, showed a different genotype frequency in two cattle subspecies, Bos taurus and Bos indicus. Cloning of the TLR2 gene and subsequent gene-reporter and chemokine assays revealed that this SNP, present in BS and Bos indicus breeds, resulted in a significantly higher response to mycobacterial antigens as well as tri-acylated lipopeptide ligands in general. Comparing wild-type and H326Q containing TLR2 responses, wild-type bovine TLR2 response showed clear, diminished mycobacterial antigen responses compared to human TLR2, however bovine TLR2 responses containing H326Q were found to be partially recovered compared to human TLR2. The creation of human:bovine TLR2 chimeras increased the response to mycobacterial antigens compared to the full-length bovine TLR2, but significantly reduced the response compared to the full-length human TLR2. Thus, our data, not only present evidence that TLR2 is a major PRR in the mammalian species-specific response to mycobacterial antigens, but furthermore, that there are clear differences between the response seen in different cattle breeds, which may contribute to their enhanced or reduced susceptibility to mycobacterial infection.

immunology↗

bioRxiv2020

Newly discovered tilapia cichlid fish biodiversity threatened by hybridization with non-native species

Invasive freshwater fish systems are known to readily hybridize with indigenous congeneric species, driving loss of unique and irreplaceable genetic resources. Here we reveal that newly discovered (2013-2016) evolutionarily significant populations of Korogwe tilapia (Oreochromis korogwe) from southern Tanzania are threatened by hybridization with the larger invasive Nile tilapia (Oreochromis niloticus). We use a combination of morphology, microsatellite allele frequencies and whole genome sequences to show that O. korogwe from southern lakes (Nambawala, Rutamba and Mitupa) are distinct from geographically-disjunct populations in northern Tanzania (Zigi River and Mlingano Dam). We also provide genetic evidence of O. korogwe x niloticus hybrids in three lakes and demonstrate heterogeneity in the extent of admixture across the genome. Finally, using the least admixed genomic regions we estimate that the northern and southern O. korogwe populations most plausibly diverged approximately 140,000 years ago, suggesting that the geographical separation of the northern and southern groups is not a result of a recent translocation, and instead these populations represent independent evolutionarily significant units. We conclude that these newly-discovered and phenotypically unique cichlid populations are already threatened by hybridization with an invasive species, and propose that these irreplaceable genetic resources would benefit from conservation interventions.

zoology↗

bioRxiv2020

A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework

BackgroundThe vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically-driven methods needed to process and understand these ever-growing datasets. ResultsHere we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows and trainings that not only enable users to perform one-click 10x preprocessing, but also empowers them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a wide range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal and clustering. The teaching resources cover an assortment of different concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal. ConclusionsThe reproducible and training-oriented Galaxy framework provides a sustainable HPC environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy Community provide a means for users to learn, publish and teach scRNA-seq analysis. Key PointsO_LISingle-cell RNA-seq has stabilised towards 10x Genomics datasets. C_LIO_LIGalaxy provides rich and reproducible scRNA-seq workflows with a wide range of robust tools. C_LIO_LIThe Galaxy Training Network provides tutorials for the processing of both 10x and non-10x datasets. C_LI

bioinformatics↗

bioRxiv2019

Sequencing smart: De novo sequencing and assembly approaches for non-model mammals.

BackgroundWhilst much sequencing effort has focused on key mammalian model organisms such as mouse and human, little is known about the correlation between genome sequencing techniques for non-model mammals and genome assembly quality. This is especially relevant to non-model mammals, where the samples to be sequenced are often degraded and low quality. A key aspect when planning a genome project is the choice of sequencing data to generate. This decision is driven by several factors, including the biological questions being asked, the quality of DNA available, and the availability of funds. Cutting-edge sequencing technologies now make it possible to achieve highly contiguous, chromosome-level genome assemblies, but relies on good quality high-molecular-weight DNA. The funds to generate and combining these data are often only available within large consortiums and sequencing initiatives, and are often not affordable for many independent research groups. For many researchers, value-for-money is a key factor when considering the generation of genomic sequencing data. Here we use a range of different genomic technologies generated from a roadkill European Polecat (Mustela putorius) to assess various assembly techniques on this low-quality sample. We evaluated different approaches for de novo assemblies and discuss their value in relation to biological analyses.\n\nResultsGenerally, assemblies containing more data types achieved better scores in our ranking system. However, when accounting for misassemblies, this was not always the case for Bionano and low-coverage 10x Genomics (for scaffolding only). We also find that the extra cost associated with combining multiple data types is not necessarily associated with better genome assemblies.\n\nConclusionsThe high degree of variability between each de novo assembly method (assessed from the seven key metrics) highlights the importance of carefully devising the sequencing strategy to be able to carry out the desired analysis. Adding more data to genome assemblies not always results in better assemblies so it is important to understand the nuances of genomic data integration explained here, in order to obtain cost-effective value-for-money when sequencing genomes.

genomics↗

bioRxiv2019

A Galaxy-based training resource for single-cell RNA-seq quality control and analyses.

BackgroundIt is not a trivial step to move from single-cell RNA-seq (scRNA-seq) data production to data analysis. There is a lack of intuitive training materials and easy-to-use analysis tools, and researchers can find it difficult to master the basics of scRNA-seq quality control and analysis.\n\nResultsWe have developed a range of easy-to-use scripts, together with their corresponding Galaxy wrappers, that make scRNA-seq training and analysis accessible to researchers previously daunted by the prospect of scRNA-seq analysis. The simple command-line tools and the point-and-click nature of Galaxy makes it easy to assess, visualise, and quality control scRNA-seq data.\n\nConclusionWe have developed a suite of scRNA-seq tools that can be used for both training and more in-depth analyses.

bioinformatics↗