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Belov, K.

Publications and source records attributed to Belov, K..

15 recordsLinked to original sources
bioRxiv2026

The Vertebrate Genomes Project Phase I: A global reference genome resource

The Vertebrate Genomes Project (VGP) aims to produce complete and near-error-free reference genomes for all [~]70,000 extant vertebrate species1. Organized in four phases, it progressively targets all vertebrate orders, families, genera, and eventually all species. Here we present the completion of VGP Phase I, delivering reference genomes for [~]95% of vertebrate orders, along with additional lineages within those orders, totaling 816 species and 1.6 trillion base pairs of main haplotype sequence. These genomes were assembled and annotated over an 8-year period (2018-2026) of rapid advances in genome sequencing, assembly, and annotation methods2-4, alongside the growth of associated consortium initiatives and international collaborations5-9. They represent some of the highest-quality vertebrate genomes currently available, and most have become the primary reference for their respective species in public databases. Comparative analyses across a subset of 579 species when we reached a threshold of 85% of orders allowed us to reconstruct the genome of the last common ancestor of all vertebrates 500 million years ago, identify diverse modes of sex chromosome evolution, reveal clade-specific three-dimensional genome architecture, discover methylated epigenetic landscapes across vertebrates, and provide a framework for studying gene and pseudogene evolution, immune loci, cancer-associated genes, and other trait-associated loci. Approximately a quarter of this subset are listed as Vulnerable to Critically Endangered by the IUCN Red List of Threatened Species, and have enabled more advanced genomic investigations of extinction risk. VGP Phase I delivers a reference backbone for vertebrate genomics, enabling discoveries that would otherwise remain out of reach across evolution, conservation, and medicine. Talking pointsO_LIThe flagship paper of VGP Phase I C_LIO_LIThe highest quality collection of genomes within the eukaryotic domain of life C_LIO_LIEvolution of genome sequencing technology quality throughout VGP Phase I C_LIO_LIA driver project that has been a model for multiple large-scale, high-quality reference genome projects C_LIO_LIReleases all currently unpublished genomes in Phase I from scientific study embargoes C_LIO_LIMultiple biological discoveries across the vertebrate tree of life C_LI

genomics↗
bioRxiv2025

Characterisation of pouch secretions from breeding Tasmanian devils

Tasmanian devils (Sarcophilus harrisii), like all marsupials, give birth to altricial young. Here we employ proteomic analysis to identify components of devil pouch secretions (red oil) that may contribute to offspring survival and development. Proteins were extracted from 5 samples and analysed by liquid chromatography-tandem mass spectrometry. Peptide-level evidence revealed proteins involved in a diverse set of immune pathways, including those mediating iron-ion transport, defence responses to bacteria, innate immune responses, and antigen processing. A core set of 200 proteins was identified across at least three samples, 63 of which were associated with antimicrobial or immunoregulatory functions. These included immunoglobulins, components of complement and coagulation cascade, and antimicrobial proteins and peptides. For the first time, these findings highlight the Tasmanian devils red oil secretions as a source of immune proteins likely contributing to microbiome restructuring during lactation. Moreover, the data indicate that these proteins may act synergistically in pathways triggered by immune challenges or physiological stress. In briefMicrobial shifts in the Tasmanian devil pouch are critical for establishing a protective environment for the developing joey. This study confirms that Tasmanian devil red oil contains a diverse array of immune proteins that likely contribute to these microbial shifts.

zoology↗
bioRxiv2025

When Cells Rebel: a comparative genomics investigation into marsupial cancer susceptibility

Cancer is ubiquitous in multicellular life, yet susceptibility varies significantly between species. Previous studies have shown a genetic basis for cancer resistance in many species, but few studies have investigated the inverse: why some species are particularly susceptible to cancer. The Dasyuridae are a family of carnivorous marsupials that are frequently reported as having high rates of cancer prevalence. We hypothesised that this high susceptibility also has a genetic basis. To investigate this, we generated reference genomes for the kowari (Dasyuroides byrnei), a dasyurid species with one of the highest rates of reported cancer prevalence among mammals, and a non-dasyurid marsupial, the eastern barred bandicoot (Perameles gunnii). We used these to perform a comparative genomics analysis alongside nine previously assembled reference genomes: four dasyurid species and five non-dasyurid marsupial species. Genomes were annotated using FGENESH++ and assigned to orthogroups for input to CAFE (Computational Analysis of gene Family Evolution) analysis to identify gene families that had undergone significant expansions or contractions in each lineage. In the dasyurids, we identified large expansions in Ras genes, a family of oncogenes. Interestingly, a similar expansion of Ras genes was also identified in the bandicoot and bilby. These genes were primarily expressed in tissues such as testes, ovaries and yolk sac, so we hypothesise they serve a reproductive role. Future work is required to identify the potential roles of oncogene expansions in cancer susceptibility in these marsupial species.

genomics↗
bioRxiv2025

Boost or Bust? The impact of supplementation on functional genetic diversity and selective processes in Tasmanian devils

Translocating individuals into existing populations of conspecifics can support threatened species by increasing population size, maintaining genetic diversity, and reducing the risk of inbreeding. However, for species whose adaptive potential is compromised due to ongoing threats, like disease, the outcome of such management interventions becomes more complex. The Tasmanian devil (Sarcophilus harrisii) is a prime example, where the emergence of Devil Facial Tumour Disease (DFTD) has led to significant population declines, raising concerns about their long-term survival. It is therefore critical to understand if the introduction of new functional genetic variants through supplementation actions enhances, or potentially hinders, their long-term persistence. We investigated changes in functional gene diversity at both the population- and individual-levels, pre and post supplementation, across multiple wild devil sites (four supplemented and four not supplemented). We found that functional diversity increased post supplementation. Though the magnitude of change was varied among sites, a similar site-specific pattern was also evident in genome-wide diversity. Importantly, we saw no evidence of swamping of local alleles or those putatively associated with DFTD regressions. This is likely due to the source population representing the broad wild genetic diversity and supplementations facilitating gene flow across the current fragmented landscape. Continued and long-term monitoring at multiple wild sites will be necessary to determine whether future generations retain this introduced genetic variation.

genomics↗
bioRxiv2025

Inbreeding and resultant homozygosity across key inflammation and DNA repair genes linked to chlamydial infection in New South Wales koalas

Inbreeding and resultant homozygosity can reduce genetic diversity and increase disease susceptibility. Koalas (Phascolarctos cinereus) are one species suffering genomic diversity loss and inbreeding and concurrent significant disease pressure (particularly chlamydiosis). Using 259 whole genomes with a pathogen sampling regime we identify potential links between inbreeding, genome-wide variation and chlamydial infection. We found a general trend of reduced genomic diversity and increased inbreeding from north to south across six sites in New South Wales. A genome-wide association study of 153 individuals from sites with known Chlamydia pecorum presence were used to investigate the potential relationship between inbreeding and infection. Chlamydia positive individuals (average FH = 0.026) were significantly more inbred than Chlamydia negative individuals (average FH= -0.0051) (t = - 2.31, df = 151, p-value = 0.022). We identified several genes involved in host-pathogen interactions and DNA mismatch repair within in runs of homozygosity that were unique to Chlamydia positive individuals. Interestingly, populations considered putatively Chlamydia-free had similar allele frequencies across candidate loci as Chlamydia positive individuals. Combined with gene flow analyses, this result suggests that isolation may have protected these populations more than harbouring alleles conferring infection resilience and supports the concept that disease should be carefully considered in any conservation measures that increase connectivity or translocations. Our genome-wide approach has identified several avenues for investigations into the pathogenesis of Chlamydia infection and chlamydiosis. We showcase the value of high-quality re-sequenced genomes for understanding the implications of inbreeding, genomic diversity loss, and infection susceptibility, all universal problems for threatened species.

genomics↗
bioRxiv2024

Temporal loss of genome-wide and immunogenetic diversity in a near-extinct parrot

Loss of genetic diversity threatens a species adaptive potential and long-term resilience. Predicted to be extinct by 2038, the orange-bellied parrot (Neophema chrysogaster) is a Critically Endangered migratory bird threatened by numerous viral, bacterial and fungal diseases. The species has undergone multiple population crashes, reaching a low of three wild-born females and 13 males in 2016 and is now represented by only a single wild population and individuals in the captive breeding program. Here we used our high-quality long-read reference genome, and contemporary and historical resequenced genomes from as early as 1829, to track the long-term genomic erosion and immunogenetic diversity decline in this species. 62% of genomic diversity was lost between historical (mean autosomal heterozygosity = 0.00149 {+/-} 0.000699 SD) and contemporary (0.00057 {+/-} 0.000026) parrots. A greater number and length of runs of homozygosity in contemporary samples was also observed. A temporal reduction of the number of alleles at Toll-like receptor genes was found (historical average alleles = 5.78 {+/-} 2.73; contemporary = 3.89 {+/-} 2.10), potentially exacerbating disease susceptibility in the contemporary population. Of particular concern is the new threat of avian influenza strain (HPAI) to Australia. We discuss the conservation implications of our findings and propose that hybridization and synthetic biology may be required to address the catastrophic loss of genetic diversity that has occurred this species in order to prevent extinction. Significance statementOrange-bellied parrots (Neophema chrysogaster) face a dire future, with extinction predicted by 2038 due to severe genetic diversity loss. This Critically Endangered species, now reduced to a single wild population and a captive breeding program, has lost 62% of its genomic diversity since 1829. Contemporary samples show a decline in immunogenetic diversity and signs of very recent inbreeding. Meaning birds today are more susceptible to disease events than birds a hundred years ago. Conservation efforts must consider hybridization and synthetic biology to counteract the catastrophic loss of genetic diversity to ensure the species survival. Our study underscores the urgent need for innovative strategies to preserve the adaptive potential and resilience of the orange-bellied parrot and other species in similar situations.

genomics↗
bioRxiv2023

Multi-omics resources for the Australian southern stuttering frog (Mixophyes australis) reveal assorted antimicrobial peptides

The number of genome-level resources for non-model species continues to rapidly expand. However, frog species remain underrepresented, with up to 90% of frog genera having no genomic or transcriptomic data. Here, we assemble the first genomic and transcriptomic resources for the recently described southern stuttering frog (Mixophyes australis). The southern stuttering frog is ground-dwelling, inhabiting naturally vegetated riverbanks in south-eastern Australia. Using PacBio HiFi long-read sequencing and Hi-C scaffolding, we generated a high-quality genome assembly, with a scaffold N50 of 369.3 Mb and 95.1% of the genome contained in twelve scaffolds. Using this assembly, we identified the mitochondrial genome, and assembled six tissue-specific transcriptomes. We also bioinformatically characterised novel sequences of two families of antimicrobial peptides (AMPs) in the southern stuttering frog, the cathelicidins and {beta}-defensins. While traditional peptidomic approaches to peptide discovery have typically identified one or two AMPs in a frog species from skin secretions, our bioinformatic approach discovered 12 cathelicidins and two {beta}-defensins that were expressed in a range of tissues. We investigated the novelty of the peptides and found diverse predicted activities. Our bioinformatic approach highlights the benefits of multi-omics resources in peptide discovery and contributes valuable genomic resources in an under-represented taxon.

genomics↗
bioRxiv2022

Genome assembly of the numbat (Myrmecobius fasciatus), the only termitivorous marsupial

The numbat (Myrmecobius fasciatus) is a critically endangered Australian marsupial, and the last surviving member of the Myrmecobiidae family. The numbat regularly undergoes torpor and is unique amongst marsupials as it is the only diurnal and termitivorous species. Here we sequenced the first draft genome of the numbat using 10x Genomics chromium linked-read technology, resulting in a 3.42 Gbp genome with a scaffold N50 of 223 Kbp. A global transcriptome from liver, lung and tongue was also generated to aid genome annotation with Fgenesh++, identifying 21,465 protein-coding genes and 78.7% complete mammalian BUSCOs. To investigate adaptation to the numbats termitivorous diet and arid/semi-arid range, we interrogated the most highly expressed transcripts within the tongue and manually annotated taste, vomeronasal and aquaporin gene families. Antimicrobial proteins and proteins involved in digestion were highly expressed in the tongue, as expected. Similarly, umami taste receptors were also expressed in the tongue, however sweet taste receptors were not expressed in this tissue. This pattern of taste receptor expression, combined with the putative contraction of the bitter taste receptor gene repertoire in the numbat genome, may indicate a potential evolutionary adaptation to their specialized termitivorous diet. Vomeronasal and aquaporin gene repertoires were similar to other marsupials and have not undergone expansion or contraction. The draft numbat genome is a valuable tool for conservation and can be applied to population genetics/genomics studies and to investigate the unique biology of this interesting species.

genomics↗
bioRxiv2021

A reference genome for the critically endangered woylie, Bettongia penicillata ogilbyi

Biodiversity is declining globally, and Australia has one of the worst extinction records for mammals. The development of sequencing technologies means that genomic approaches are now available as important tools for wildlife conservation and management. Despite this, genome sequences are available for only 5% of threatened Australian species. Here we report the first reference genome for the woylie (Bettongia penicillata ogilbyi), a critically endangered marsupial from Western Australia, and the first genome within the Potoroidae family. The woylie reference genome was generated using Pacific Biosciences HiFi long-reads, resulting in a 3.39 Gbp assembly with a scaffold N50 of 6.49 Mbp and 86.5% complete mammalian BUSCOs. Assembly of a global transcriptome from pouch skin, tongue, heart and blood RNA-seq reads was used to guide annotation with Fgenesh++, resulting in the annotation of 24,655 genes. The woylie reference genome is a valuable resource for conservation, management and investigations into disease-induced decline of this critically endangered marsupial.

genomics↗
bioRxiv2021

Epigenetic predictors of maximum lifespan and other life history traits in mammals

Maximum lifespan of a species is the oldest that individuals can survive, reflecting the genetic limit of longevity in an ideal environment. Here we report methylation-based models that accurately predict maximum lifespan (r=0.89), gestational time (r=0.96), and age at sexual maturity (r=0.87), using cytosine methylation patterns collected from over 12,000 samples derived from 192 mammalian species. Our epigenetic maximum lifespan predictor corroborated the extended lifespan in growth hormone receptor knockout mice and rapamycin treated mice. Across dog breeds, epigenetic maximum lifespan correlates positively with breed lifespan but negatively with breed size. Lifespan-related cytosines are located in transcriptional regulatory regions, such as bivalent chromatin promoters and polycomb-repressed regions, which were hypomethylated in long-lived species. The epigenetic estimators of maximum lifespan and other life history traits will be useful for characterizing understudied species and for identifying interventions that extend lifespan.

evolutionary biology↗
bioRxiv2021

DNA Methylation Networks Underlying Mammalian Traits

Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an unbiased clustering of individual cytosines into 55 modules and identified 31 modules related to primary traits including age, species lifespan, sex, adult species weight, tissue type and phylogenetic order. Analysis of the correlation between DNA methylation and species allowed us to construct phyloepigenetic trees for different tissues that parallel the phylogenetic tree. In addition, while some stable cytosines reflect phylogenetic signatures, others relate to age and lifespan, and in many cases responding to anti-aging interventions in mice such as caloric restriction and ablation of growth hormone receptors. Insights uncovered by this investigation have important implications for our understanding of the role of epigenetics in mammalian evolution, aging and lifespan.

evolutionary biology↗
bioRxiv2021

Universal DNA methylation age across mammalian tissues

Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence. SUMMARYThis study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.

developmental biology↗
bioRxiv2020

The first Antechinus reference genome provides a resource for investigating the genetic basis of semelparity and age-related neuropathologies

Antechinus are a genus of mouse-like marsupials that exhibit a rare reproductive strategy known as semelparity and also naturally develop age-related neuropathologies similar to those in humans. We provide the first annotated antechinus reference genome for the brown antechinus (Antechinus stuartii). The reference genome is 3.3Gb in size with a scaffold N50 of 73Mb and 93.3% complete mammalian BUSCOs. Using bioinformatic methods we assign scaffolds to chromosomes and identify 0.78Mb of Y-chromosome scaffolds. Comparative genomics revealed interesting expansions in the NMRK2 gene and the protocadherin gamma family, which have previously been associated with aging and age-related dementias respectively. Transcriptome data displayed expression of common Alzheimers related genes in the antechinus brain and highlight the potential of utilising the antechinus as a future disease model. The valuable genomic resources provided herein will enable future research to explore the genetic basis of semelparity and age-related processes in the antechinus.

genomics↗
bioRxiv2018

Characterisation of the faecal virome of captive and wild Tasmanian devils using virus-like particles metagenomics and meta-transcriptomics

BackgroundThe Tasmanian devil is an endangered carnivorous marsupial threatened by devil facial tumour disease (DFTD). While research on DFTD has been extensive, little is known about the viruses present in devils, and whether any of these are of potential conservation relevance for this endangered species.\n\nMethodsUsing both metagenomics based on virus-like particle (VLP) enrichment and sequence-independent amplification (VLP metagenomics), and meta-transcriptomics based on bulk RNA sequencing, we characterised and compared the faecal viromes of captive and wild Tasmanian devils.\n\nResultsA total of 54 devil faecal samples collected from captive (n = 2) and wild (n = 4) populations were processed for virome characterisation using both approaches. We detected many novel, highly divergent viruses, including vertebrate viruses, bacteriophage and other dietary associated plant and insect viruses. In total, 18 new vertebrate viruses, including novel sapelovirus, astroviruses, bocaviruses, papillomaviruses and gammaherpesvirus were identified, as well as known mammalian pathogens including rabbit haemorrhagic disease virus 2 (RHDV2). Captive devils showed significantly lower levels of viral diversity than wild devils. Comparison of the two methodological approaches revealed substantial differences in the number and types of viruses detected, with meta-transcriptomics mainly identifying RNA viruses, and VLP metagenomics largely identifying DNA viruses.\n\nConclusionThis study has greatly expanded our knowledge of eukaryotic viruses in the Tasmanian devil and provides important baseline information that will contribute to the conservation and captive management of this endangered species. In addition, our results showed that a combination of VLP metagenomics and meta-transcriptomics may be a more comprehensive approach to virome characterisation than either method alone.

molecular biology↗