Biology subjects

Martin, F. J.

Publications and source records attributed to Martin, F. J..

At least 19 recordsLinked to original sources

bioRxiv2025

Complete de novo assembly and re-annotation of the zebrafish genome

The zebrafish (Danio rerio) is widely used in vertebrate research, but its reference genome assembly has contained extensively unresolved regions across both euchromatic and heterochromatic compartments. The previous reference genome assembly, GRCz11, consisted of 19,725 contigs assembled into 1,917 scaffolds. Recent advances in both long-read sequencing technologies and genome assembly algorithms have made "complete" genome assemblies possible for the first time. We used homozygous fish from two lab strains, "Tubingen" and "AB," for de novo genome assemblies. The new assemblies incorporated 7% more genomic sequence than GRCz11 and an additional 130 million bases of previously unassembled sequence. RefSeq annotation incorporating newly generated Iso-Seq cDNA sequences have added notable increases in mRNAs (68%), lncRNAs (47%), and misc_RNAs (1099%). Two assemblies have been elevated to reference genome status (GRCz12tu and GRCz12ab). We generated an additional 40 draft haplotypes to create a zebrafish pangenome resource and demonstrate its utility for variant analysis.

genomics↗

bioRxiv2025

The Onychomys pangenome reveals the unique molecular adaptations that confer toxin resistance

Novel traits enable many rodents to thrive in extreme environmental niches. Predatory grasshopper mice (Onychomys sp.) have co-evolved resistance to painful and lethal neurotoxins produced by their scorpion prey. Previous work reported that grasshopper mice have structural and functional modifications in sodium channel Nav1.8 that block the effect of painful toxins. However, key questions remain about the molecular adaptations underlying toxin resistance. We produced the first high-quality reference genomes and annotations for Onychomys species and Peromyscus eremicus. We implemented a comprehensive pipeline to detect positive selection across genome-scale datasets and identified Onychomys-specific mutations in Nav1.3 (Scn3a), a sodium channel gene expressed in the central nervous system and the peripheral sensory system after nerve damage. We detected an Onychomys-specific tandem gene duplication of the Cblif gene, which encodes a glycoprotein crucial for vitamin B12 absorption. This adaptation likely supports the species dietary specialisation and modified stomach morphology, where parietal cells expressing Cblif are especially numerous. Our study provides a key step for establishing the Onychomys species as a model system for studying toxin resistance, alternative pain phenotypes, and behavioural traits related to predator-prey interactions.

genomics↗

bioRxiv2025

The mouse pangenome reveals the structural complexity of the murine protein coding landscape

We present the first mouse pangenome consisting of 17 high-quality inbred mouse strain genomes with complete annotation. This collection includes 12 widely used classical laboratory strains and 5 wild-derived strains. We have fully resolved previously incomplete genomic regions, including the major histocompatibility complex (MHC), the defensin cluster, T-cell receptor, and Ly49 complexes. Hundreds of non-reference genes identified in previous publications not found in GRCm39, like Defa1, Raet1a, and Klra20 (Ly49T), were localised in the new reference genomes. We conducted the first genome-wide scan of variable number tandem repeats (VNTRs) within the coding regions of mice, identifying over 400 genes with VNTR polymorphisms up to more than 600 repeat copies and repeat units reaching 990 nucleotides. Our strain-specific annotations enhance RNA-Seq analyses, as demonstrated in PWK/PhJ, where we observed a 5.1% improvement in read mapping and expression level differences in 2.1% of coding genes compared to using GRCm39.

genomics↗

bioRxiv2025

The genome sequence of the hemlock woolly adelgid, Adelges tsugae Annand 1924

The genome of the hemlock woolly adelgid (Adelges tsugae) is presented in 10 chromosomal pseudomolecules along with 132 unplaced scaffolds for a combined length of 216.56 Mb. The genome is highly contiguous, with a benchmarking universal single-copy orthologs (BUSCO) completion score of 98.25%, an N50 of 20.54 Mb, and the longest scaffold 37.41 Mb in length. On the basis of chromosomal synteny with other aphid genomes, the hemlock woolly adelgids genome is composed of 8 autosomes and two sex (X) chromosomes. Annotation of the assembly identified 11,800 coding genes, 1,930 non-coding genes, and 20,403 mRNA transcripts. The mitogenome is also presented in a single, annotated, circular contig 25,980 bases in length. Species taxonomyEukaryota; Metazoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Paraneoptera; Hemiptera; Sternorrhyncha; Aphidomorpha; Adelgoidea; Adelgidae; Adelges; Annandina; Adelges (Annandina) tsugae Annand, 1924 (NCBI:txid357502)

genomics↗

bioRxiv2024

GENCODE: massively expanding the lncRNA catalog through capture long-read RNA sequencing

Accurate and complete gene annotations are indispensable for understanding how genome sequences encode biological functions. For more than twenty years, the GENCODE consortium has developed reference annotations for the human and mouse genomes, becoming a foundation for biomedical and genomics communities worldwide. Nevertheless, collections of important yet poorly-understood gene classes like long non-coding RNAs (lncRNAs) remain incomplete and scattered across multiple, uncoordinated catalogs. To address this, GENCODE has undertaken the most comprehensive lncRNA annotation effort to date. This is founded on the manually supervised computational annotation of full-length targeted long-read sequencing, on matched embryonic and adult tissues, of orthologous regions in human and mouse. Altogether 17,931 human genes (140,268 transcripts) and 22,784 mouse genes (136,169 transcripts) have been added to the GENCODE catalog representing a 2-fold and 6-fold growth in transcripts, respectively - the greatest increase in the number of annotated human genes since the sequencing of the human genome. Our targeted design assigned human-mouse orthologs at a rate beyond previous studies, tripling the number of human disease-associated lncRNAs that have mouse orthologs. Novel lncRNA genes consistently exhibit biological signals of functionality, and they greatly enhance the functional interpretability of the human genome. While poorly expressed in bulk RNA-Seq samples, many of them are highly expressed in specific cell populations, maybe even contributing to cell-type determination. The expanded GENCODE lncRNA annotations mark a critical step toward deciphering the human and mouse genomes.

genomics↗

bioRxiv2023

Continent-wide genomic analysis of the African buffalo (Syncerus caffer).

The African buffalo (Syncerus caffer) is a wild bovid with a historical distribution across much of sub-Saharan Africa. Genomic analysis can provide insights into the evolutionary history of the species, and the key selective pressures shaping populations, including assessment of population level differentiation, population fragmentation, and population genetic structure. In this study we generated the highest quality de novo genome assembly (2.65 Gb, scaffold N50 69.17 Mb) of African buffalo to date, and sequenced a further 195 genomes from across the species distribution. Principal component and admixture analyses provided surprisingly little support for the currently described four subspecies, but indicated three main lineages, in Western/Central, Eastern and Southern Africa, respectively. Estimating Effective Migration Surfaces analysis suggested that geographical barriers have played a significant role in shaping gene flow and the population structure. Estimated effective population sizes indicated a substantial drop occurring in all populations 5-10,000 years ago, coinciding with the increase in human populations. Finally, signatures of selection were enriched for key genes associated with the immune response, suggesting infectious disease exert a substantial selective pressure upon the African buffalo. These findings have important implications for understanding bovid evolution, buffalo conservation and population management.

genomics↗

bioRxiv2023

A revamped rat reference genome improves the discovery of genetic diversity in laboratory rats

The seventh iteration of the reference genome assembly for Rattus norvegicus-- mRatBN7.2--corrects numerous misplaced segments and reduces base-level errors by approximately 9-fold and increases contiguity by 290-fold compared to its predecessor. Gene annotations are now more complete, significantly improving the mapping precision of genomic, transcriptomic, and proteomics data sets. We jointly analyzed 163 short-read whole genome sequencing datasets representing 120 laboratory rat strains and substrains using mRatBN7.2. We defined [~]20.0 million sequence variations, of which 18.7 thousand are predicted to potentially impact the function of 6,677 genes. We also generated a new rat genetic map from 1,893 heterogeneous stock rats and annotated transcription start sites and alternative polyadenylation sites. The mRatBN7.2 assembly, along with the extensive analysis of genomic variations among rat strains, enhances our understanding of the rat genome, providing researchers with an expanded resource for studies involving rats.

genomics↗

bioRxiv2023

Lepidoptera genomics based on 88 chromosomal reference sequences informs population genetic parameters for conservation

Butterflies and moths (Lepidoptera) are one of the most ecologically diverse and speciose insect orders, with more than 157,000 described species. However, the abundance and diversity of Lepidoptera are declining worldwide at an alarming rate. As few Lepidoptera are explicitly recognised as at risk globally, the need for conservation is neither mandated nor well-evidenced. Large-scale biodiversity genomics projects that take advantage of the latest developments in long-read sequencing technologies offer a valuable source of information. We here present a comprehensive, reference-free, whole-genome, multiple sequence alignment of 88 species of Lepidoptera. We show that the accuracy and quality of the alignment is influenced by the contiguity of the reference genomes analysed. We explored genomic signatures that might indicate conservation concern in these species. In our dataset, which is largely from Britain, many species, in particular moths, display low heterozygosity and a high level of inbreeding, reflected in medium (0.1 - 1 Mb) and long (> 1 Mb) runs of homozygosity. Many species with low inbreeding display a higher masked load, estimated from the sum of rejected substitution scores at heterozygous sites. Our study shows that the analysis of a single diploid genome in a comparative phylogenetic context can provide relevant genetic information to prioritise species for future conservation investigation, particularly for those with an unknown conservation status.

genomics↗

bioRxiv2023

Hagfish genome illuminates vertebrate whole genome duplications and their evolutionary consequences

Whole genome duplications (WGDs) are major events that drastically reshape genome architecture and are causally associated with organismal innovations and radiations1. The 2R Hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution2, 3. However, the veracity and timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved4-6 and whether these WGD events underlie vertebrate phenotypic diversification remains elusive7. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and the 2R event occurred in the gnathostome stem-lineage in the late Cambrian after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced two additional, independent genome duplications (herein CR1 and CR2). Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only after the 2R event, questioning the general expectation that WGDs lead to leaps of morphological complexity7.

genomics↗

bioRxiv2022

A Draft Human Pangenome Reference

The Human Pangenome Reference Consortium (HPRC) presents a first draft human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence and are more than 99% accurate at the structural and base-pair levels. Based on alignments of the assemblies, we generated a draft pangenome that captures known variants and haplotypes, reveals novel alleles at structurally complex loci, and adds 119 million base pairs of euchromatic polymorphic sequence and 1,529 gene duplications relative to the existing reference, GRCh38. Roughly 90 million of the additional base pairs derive from structural variation. Using our draft pangenome to analyze short-read data reduces errors when discovering small variants by 34% and boosts the detected structural variants per haplotype by 104% compared to GRCh38-based workflows, and by 34% compared to using previous diversity sets of genome assemblies.

genomics↗

bioRxiv2022

The evolution of two transmissible cancers in Tasmanian devils

Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analysing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982-1989), and DFT2 in 2011 (2009-2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study illuminates the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.

cancer biology↗

bioRxiv2022

The swan genome and transcriptome: its not all black and white

The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related Northern Hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious disease, notably infectious diseases from which Australia has been largely shielded. Indeed, unlike Mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to severe highly pathogenic avian influenza (HPAI). Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. Here, we generate the first chromosome-length annotated black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We used these genomes and transcriptomes, to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to HPAI. We also implicate genetic differences in SLC45A2 in the iconic plumage of the Australian black swan. Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat the survival of the black swan would be in significant peril.

genomics↗

bioRxiv2021

Coiled coils 9-to-5: Rational de novo design of α-helical barrels with tunable oligomeric states

The rational design of linear peptides that assemble controllably and predictably in water is challenging. Sequences must encode unique target structures and avoid alternative states. However, the stabilizing and discriminating non-covalent forces available are weak in water. Nonetheless, for -helical coiled-coil assemblies considerable progress has been made in rational de novo design. In these, sequence repeats of nominally hydrophobic (h) and polar (p) residues, hpphppp, direct the assembly of amphipathic helices into dimeric to tetrameric bundles. Expanding this pattern to hpphhph can produce larger -helical barrels. Here, we show that pentamers to nonamers are achieved simply by varying the residue at one of these h sites. In L/I-K-E-I-A-x-Z repeats, decreasing the size of Z from threonine to serine to alanine to glycine gives progressively larger oligomers. X-ray crystal structures of the resulting -helical barrels rationalize this: side chains at Z point directly into the helical interfaces, and smaller residues allow closer helix contacts and larger assemblies.

biochemistry↗

bioRxiv2020

The Ensembl COVID-19 resource: Ongoing integration of public SARS-CoV-2 data

The COVID-19 pandemic has seen unprecedented use of SARS-CoV-2 genome sequencing for epidemiological tracking and identification of emerging variants. Understanding the potential impact of these variants on the infectivity of the virus and the efficacy of emerging therapeutics and vaccines has become a cornerstone of the fight against the disease. To support the maximal use of genomic information for SARS-CoV-2 research, we launched the Ensembl COVID-19 browser, incorporating a new Ensembl gene set, multiple variant sets (including novel variation calls), and annotation from several relevant resources integrated into the reference SARS-CoV-2 assembly. This work included key adaptations of existing Ensembl genome annotation methods to model ribosomal slippage, stringent filters to elucidate the highest confidence variants and utilisation of our comparative genomics pipelines on viruses for the first time. Since May 2020, the content has been regularly updated and tools such as the Ensembl Variant Effect Predictor have been integrated. The Ensembl COVID-19 browser is freely available at https://covid-19.ensembl.org.

bioinformatics↗

bioRxiv2019

The tuatara genome: insights into vertebrate evolutionfrom the sole survivor of an ancient reptilian order

The tuatara (Sphenodon punctatus), the only living member of the archaic reptilian order Rhynchocephalia (Sphenodontia) once widespread across Gondwana, is an iconic and enigmatic terrestrial vertebrate endemic to New Zealand. A key link to the now extinct stem reptiles from which dinosaurs, modern reptiles, birds and mammals evolved, the tuatara provides exclusive insights into the ancestral amniotes. The tuatara genome, at [~]5 Gbp, is among the largest vertebrate genomes assembled. Analysis of this genome and comparisons to other vertebrates reinforces the uniqueness of the tuatara. Phylogenetic analyses indicate tuatara diverged from the snakes and lizards [~]250 MYA. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Genome sequence analysis identifies expansions of protein, non-protein-coding RNA families, and repeat elements, the latter of which show an extraordinary amalgam of reptilian and mammalian features. Sequencing of this genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. It also provides important insights into both the technical challenges and the cultural obligations associated with genome sequencing.

genomics↗

bioRxiv2019

Cell type specific novel lincRNAs and circRNAs in the BLUEPRINT haematopoietic transcriptomes atlas.

Transcriptional profiling of hematopoietic cell subpopulations has helped characterize the developmental stages of the hematopoietic system and the molecular basis of malignant and non-malignant blood diseases for the past three decades. The introduction of high-throughput RNA sequencing has increased knowledge of the full repertoire of RNA molecules in hematopoietic cells of different types, without relying on prior gene annotation. Here, we introduce the analysis of the BLUEPRINT consortium gene expression data for mature hematopoietic cells, comprising 90 total RNA and 32 small RNA sequencing experiments, from 27 different cell types. We used these data to describe the transcriptional profile of each we used guided transcriptome assembly to extend the annotation of the transcribed genome, which led to the identification of hundreds of novel non-coding RNA genes, which display a high degree of cell type specificity. We also characterized the expression of circular RNAs and found that these are also highly cell type specific. This resource refines the active transcriptional landscape of mature hematopoietic cells, highlights abundant genes and transcriptional isoforms for each cell type, and provides valuable data and visualisation tools for the scientific community working on hematological development and diseases.

genomics↗

bioRxiv2019

Haplotype-Resolved Cattle Genomes Provide Insights Into Structural Variation and Adaptation

We present high quality, phased genome assemblies representative of taurine and indicine cattle, subspecies that differ markedly in productivity-related traits and environmental adaptation. We report a new haplotype-aware scaffolding and polishing pipeline using contigs generated by the trio binning method to produce haplotype-resolved, chromosome-level genome assemblies of Angus (taurine) and Brahman (indicine) cattle breeds. These assemblies were used to identify structural and copy number variants that differentiate the subspecies and we found variant detection was sensitive to the specific reference genome chosen. Six gene families with immune related functions are expanded in the indicine lineage. Assembly of the genomes of both subspecies from a single individual enabled transcripts to be phased to detect allele-specific expression, and to study genome-wide selective sweeps. An indicus-specific extra copy of fatty acid desaturase is under positive selection and may contribute to indicine adaptation to heat and drought.

genomics↗

bioRxiv2019

An improved pig reference genome sequence to enable pig genetics and genomics research

The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete and unresolved redundancies, short range order and orientation errors and associated misassembled genes limited its utility. We present two annotated highly contiguous chromosome-level genome assemblies created with more recent long read technologies and a whole genome shotgun strategy, one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

genomics↗