Biology subjects

Hughes, G. M.

Publications and source records attributed to Hughes, G. M..

8 recordsLinked to original sources

bioRxiv2026

A comparative genomics framework for identifying historical population bottlenecks using olfactory receptor gene evolution

Population bottlenecks reduce genetic diversity, increase the fixation of deleterious mutations and elevate extinction risk. Identifying lineages experiencing bottlenecks is a key goal of conservation genetics, facilitating the allocation of limited resources to at-risk species. Although whole-genome sequencing has improved bottleneck detection by reconstructing demographic history, these methods often require extensive population sampling, limiting their application. Previous studies of species showing population bottlenecks have reported an increased number of pseudogenes in the olfactory receptor (OR) gene family, however whether such evolutionary dynamics can be used as comparative biomarkers of genomic decline remains unknown. By quantifying the number of lineage-specific duplication and pseudogenization events, we introduce the duplication-to-loss ratio (DLR), a comparative metric exploring the rate at which chemosensory gene loss is offset by the generation of novel receptors. We characterize the chemosensory repertoires of 21 felid species, including species with known historical bottlenecks, to establish the utility of this DLR metric. Subsequently, we evaluate its usage across additional mammalian families, specifically Ursidae and Pinnipedia, to determine its utility beyond Felidae. Our DLR metric recovers several felid species with a history of genomic decline, including cheetah (Acinonyx jubatus) and black-footed cat (Felis nigripes), as well as the giant panda (Ailuropoda melanoleuca), polar bear (Ursus maritimus), Hawaiian monk seal (Neomonachus schauinslandi) and northern elephant seal (Mirounga angustirostris). Our results demonstrate the utility of the OR gene repertoire as a scalable, robust biomarker for identifying comparative population decline, prioritising species for conservation genomic investigation using only the reference genome.

genomics↗

bioRxiv2026

Expansion of Olfactory Receptor Family 14 Across Fossorial and Insectivorous Mammals

Mammals have incredibly diverse olfactory repertoires, reflected in significant copy number variation of olfactory receptor genes across species. As mammals occupy a wide range of habitats and foraging environments, it is expected that such variation is shaped by ecological niche. Indeed, several studies have shown that specific olfactory receptor gene families are associated with habitat and dietary specialization. Despite this, there is currently little known about the ecological factors driving variation of olfactory receptor family 14 (OR14) across mammals. Here, we address this gap by mining mammalian genomes to identify and classify OR14 genes across hundreds of species. By mapping OR14 variation onto dietary and habitat variables, in the context of the mammalian phylogenetic tree, we identify key factors associated with OR14 evolution across mammals. Specifically, we find that OR14 has undergone repeated expansion across independent lineages of fossorial and insectivorous mammals, suggesting that expansion of this gene family may be adaptive and driven by convergent ecological pressures. By performing principal component analysis and k-means clustering based on OR14 subfamily composition, we find that species cluster irrespective of phylogeny. Furthermore, we show that many independent myrmecophagous lineages form a single cluster, providing evidence of convergence at the sequence level, potentially driven by selection for ant/termite rich diets. Together, our results indicate that OR14 plays an important functional role in fossorial and insectivorous mammals, providing a foundation for future studies aimed at deorphaning these receptors.

evolutionary biology↗

bioRxiv2026

GENE-FAM: An automated pipeline for mining gene families and its application to MADS-box genes in Cannabis sativa

Understanding how gene families evolve can offer great insight into adaptation at the phenotypic and ecological levels. This is particularly true in plants, where transcription factor gene families are often targeted for breeding programs to improve the agronomic traits of economically important crops. While recent advances in next generation sequencing have accelerated the wealth of genomics data, there remains a lack of accessible and reproducible genome mining pipelines tailored for gene family characterisation. Here, we address this gap by developing GENE-FAM, an automated, scalable and open-source pipeline designed to mine and predict gene families based on conserved domains and motifs. To illustrate its application, we apply GENE-FAM to annotate MADS-box transcription factor genes across multiple Cannabis sativa genomes. A comprehensive set of MADS-box genes was identified across three C. sativa cultivars, including both previously annotated and newly predicted genes. Through phylogenetic analyses, we confirm that all type II MADS-box gene subfamilies represented in flowering plants are present in C. sativa. Comparing our annotations with those of Arabidopsis thaliana and Solanum lycopersicum revealed that while most MADS type II families are highly conserved, SEPALLATA-like genes have undergone diversification in C. sativa. Together, these results demonstrate the application of GENE-FAM for genome-wide identification and characterisation of gene families in non-model species, revealing novel insights into MADS-box gene family evolution in C. sativa.

genomics↗

bioRxiv2023

Title: Leveraging Base Pair Mammalian Constraint to Understand Genetic Variation and Human Disease

Although thousands of genomic regions have been associated with heritable human diseases, attempts to elucidate biological mechanisms are impeded by a general inability to discern which genomic positions are functionally important. Evolutionary constraint is a powerful predictor of function that is agnostic to cell type or disease mechanism. Here, single base phyloP scores from the whole genome alignment of 240 placental mammals identified 3.5% of the human genome as significantly constrained, and likely functional. We compared these scores to large-scale genome annotation, genome-wide association studies (GWAS), copy number variation, clinical genetics findings, and cancer data sets. Evolutionarily constrained positions are enriched for variants explaining common disease heritability (more than any other functional annotation). Our results improve variant annotation but also highlight that the regulatory landscape of the human genome still needs to be further explored and linked to disease.

genomics↗

bioRxiv2023

Evolutionary constraint and innovation across hundreds of placental mammals

Evolutionary constraint and acceleration are powerful, cell-type agnostic measures of functional importance. Previous studies in mammals were limited by species number and reliance on human-referenced alignments. We explore the evolution of placental mammals, including humans, through reference-free whole-genome alignment of 240 species and protein-coding alignments for 428 species. We estimate 10.7% of the human genome is evolutionarily constrained. We resolve constraint to single nucleotides, pinpointing functional positions, and refine and expand by over seven-fold the catalog of ultraconserved elements. Overall, 48.5% of constrained bases are as yet unannotated, suggesting yet-to-be-discovered functional importance. Using species-level phenotypes and an updated phylogeny, we associate coding and regulatory variation with olfaction and hibernation. Focusing on biodiversity conservation, we identify genomic metrics that predict species at risk of extinction.

genomics↗

bioRxiv2022

Nematodes can survive in a suspended form of life for indefinite time

Some organisms in nature have developed the ability to enter a state of suspended metabolism called cryptobiosis1 when environmental conditions are unfavorable. This state-transition requires execution of a combination of genetic and biochemical pathways1,2,3 that enable the organism to survive for prolonged periods. Recently, nematode individuals have been reanimated from Siberian permafrost after remaining in cryptobiosis. Preliminary analysis indicates that these nematodes belong to the genera Panagrolaimus and Plectus4. Here, we present precise radiocarbon dating indicating that the Panagrolaimus individuals have remained in cryptobiosis since the late Pleistocene ([~]46,000 years). Phylogenetic inference based on our genome assembly and a detailed morphological analysis demonstrate that they belong to an undescribed species, which we named Panagrolaimus n. sp. Comparative genome analysis revealed that the molecular toolkit for cryptobiosis in Panagrolaimus n. sp. and in C. elegans is partly orthologous. We show that biochemical mechanisms employed by these two species to survive desiccation and freezing under laboratory conditions are similar. Our experimental evidence also reveals that C. elegans dauer larvae can remain viable for longer periods in suspended animation than previously reported. Altogether, our findings demonstrate that nematodes evolved mechanisms potentially allowing them to suspend life over geological time scales.

genomics↗

bioRxiv2020

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low. Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

genomics↗

bioRxiv2019

Six new reference-quality bat genomes illuminate the molecular basis and evolution of bat adaptations

Bats account for ~20% of all extant mammal species and are considered exceptional given their extraordinary adaptations, including biosonar, true flight, extreme longevity, and unparalleled immune systems. To understand these adaptations, we generated reference-quality genomes of six species representing the key divergent lineages. We assembled these genomes with a novel pipeline incorporating state-of-the-art long-read and long-range sequencing and assembly techniques. The genomes were annotated using a maximal evidence approach, de novo predictions, protein/mRNA alignments, Iso-seq long read and RNA-seq short read transcripts, and gene projections from our new TOGA pipeline, retrieving virtually all (>99%) mammalian BUSCO genes. Phylogenetic analyses of 12,931 protein coding-genes and 10,857 conserved non-coding elements identified across 48 mammalian genomes helped to resolve bats closest extant relatives within Laurasiatheria, supporting a basal position for bats within Scrotifera. Genome-wide screens along the bat ancestral branch revealed (a) selection on hearing-involved genes (e.g LRP2, SERPINB6, TJP2), which suggest that laryngeal echolocation is a shared ancestral trait of bats; (b) selection (e.g INAVA, CXCL13, NPSR1) and loss of immunity related proteins (e.g. LRRC70, IL36G), including pro-inflammatory NF-kB signalling; and (c) expansion of the APOBEC family, associated with restricting viral infection, transposon activity and interferon signalling. We also identified unique integrated viruses, indicating that bats have a history of tolerating viral pathogens, lethal to other mammal species. Non-coding RNA analyses identified variant and novel microRNAs, revealing regulatory relationships that may contribute to phenotypic diversity in bats. Together, our reference-quality genomes, high-quality annotations, genome-wide screens and in-vitro tests revealed previously unknown genomic adaptations in bats that may explain their extraordinary traits.

genomics↗