Biology subjects

Silver, L. W.

Publications and source records attributed to Silver, L. W..

7 recordsLinked to original sources

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↗

bioRxiv2025

Escaping inbreeding: the demographic path to genetic recovery

Bottlenecks pose a major threat to species persistence by reducing genetic diversity and increasing inbreeding. Although evolutionary theory suggests these constraints can be overcome, empirical evidence has largely come from invasive species. Here, we analyse whole-genome data from 418 koalas (Phascolarctos cinereus) across 27 populations to reconstruct demographic histories and examine rare genetic variation. We find that northern populations retain higher genetic diversity, while southern populations, despite severe bottlenecks, exhibit larger and increasing effective population sizes (Ne). This apparent contradiction is explained by increased reshuffling of genetic variation through recombination, and the accumulation of rare alleles during recent demographic expansion. Our findings demonstrate that rapid population growth can substantially elevate Ne, offering an evolutionary pathway by which threatened populations may "escape" the genetic risks of inbreeding.

evolutionary biology↗

bioRxiv2025

Mutation rate estimate and population genomic analysis reveals decline of koalas prior to human arrival

The koala (Phascolarctos cinereus), an iconic Australian marsupial, has experienced substantial historical and contemporary population declines. Identifying the drivers of these declines has been hindered by limited genomic data and by uncertainty regarding the koala mutation rate. Here, we provide the first direct estimate of the koala mutation rate, based on four parent-offspring trios, yielding a mean of 6.12x10{square}{square} mutations per base pair per generation (95% confidence interval: 5.03-7.45x10{square}{square}). Using this estimate of the rate, we reconstructed the demographic history of koalas using 458 whole-genome sequences sampled across their entire range. Our results refine the estimated timing of past changes in population size, suggesting a large decline beginning [~]100 kya, before the arrival of modern humans in Australia. The koala population then split into five genetic populations 6-30 kya, which are now spread across >3500 km on the east coast of Australia. We also use the koala mutation rate to infer recombination maps for each population, confirming lower recombination rates in marsupials than in eutherian mammals. These findings provide critical insights into the evolutionary history of koalas, while highlighting the impact of using species-specific evolutionary rates in the inference of demographic histories and recombination landscapes. Our estimates of the genome-wide mutation rate and population-specific recombination maps for koalas provide valuable resources for future evolutionary and conservation analyses of marsupials.

evolutionary biology↗

bioRxiv2025

Adaptively integrated sequencing and assembly of near-complete genomes

Advances in long-read sequencing (LRS) and assembly algorithms have made it possible to create highly complete genome assemblies for humans, animals and plants. However, ongoing development is needed to improve accessibility, affordability, and assembly quality and completeness. Cornetto is a new strategy in which we use programmable selective nanopore sequencing to focus LRS data production onto the unsolved regions of a nascent assembly. This improves assembly quality and streamlines the process, both for humans and non-human vertebrates. Cornetto enables us to generate highly complete diploid human genome assemblies using only nanopore LRS data, surpassing the quality of previous efforts at a fraction of the cost. Cornetto enables genome assembly from challenging sample types like human saliva. Finally, we obtain accurate assemblies for clinically-relevant repetitive loci at the extremes of the genome, demonstrating valid approaches for genetic diagnosis in facioscapulohumeral muscular dystrophy (FSHD) and MUC1-autosomal dominant tubulointerstitial kidney disease (MUC1-ADTKD).

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↗