Temporal Loss of Genome-Wide and Immunogenetic Diversity in a Near-Extinct Parrot

Type: Journal article

Reference: Silver LW, Farquharson KA, Peel E, Gilbert MTP, Belov K, Morales HE, Hogg CJ. Temporal Loss of Genome-Wide and Immunogenetic Diversity in a Near-Extinct Parrot. Mol Ecol. 2025 Mar 25:e17746. doi: 10.1111/mec.17746.

Abstract

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 (N = 19) and historical (N = 16) 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 were also observed. A temporal reduction in 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 hybridisation and synthetic biology may be required to address the catastrophic loss of genetic diversity that has occurred in this species in order to prevent extinction.

AMPed Up Immunity: 418 Whole Genomes Reveal Intraspecific Diversity of Koala Antimicrobial Peptides

Type: Journal article

Reference: Petrohilos C, Peel E, Silver LW, Belov K, Hogg CJ. AMPed up immunity: 418 whole genomes reveal intraspecific diversity of koala antimicrobial peptides. Immunogenetics. 2025 Jan 8;77(1):11. doi: 10.1007/s00251-024-01368-2.

Abstract

Characterising functional diversity is a vital element to understanding a species’ immune function, yet many immunogenetic studies in non-model organisms tend to focus on only one or two gene families such as the major histocompatibility complex (MHC) or toll-like receptors (TLR). Another interesting component of the eukaryotic innate immune system is the antimicrobial peptides (AMPs). The two major groups of mammalian AMPs are cathelicidins and defensins, with the former having undergone species-specific expansions in marsupials. Here, we utilised data from 418 koala whole genomes to undertake the first comprehensive analysis of AMP diversity across a mammalian wildlife species’ range. Overall, allelic diversity was lower than other immune gene families such as MHC, suggesting that AMPs are more conserved, although balancing selection was observed in PhciDEFB12. Some non-synonymous SNPs in the active peptide are predicted to change AMP function through stop gains, change in structure, and increase in peptide charge. Copy number variants (CNVs) were observed in two defensins and one cathelicidin. Interestingly, the most common CNV was the duplication of PhciCATH5, a cathelicidin with activity against chlamydia, which was more common in the southern part of the species range than the north. AMP copy number is correlated with expression levels, so we hypothesise that there is a selective pressure from chlamydia for duplications in PhciCATH5. Future studies should use phenotypic metadata to assess the functional impacts of this gene duplication.

Bioactive components in the marsupial pouch and milk

Type: Journal article

Reference: Jayamanna Mohottige MW, Gardner CE, Nye-Wood MG, Farquharson KA, Juhász A, Belov K, Hogg CJ, Peel E, Colgrave ML. Bioactive components in the marsupial pouch and milk. Nutr Res Rev. 2024 Nov 18:1-12. doi: 10.1017/S0954422424000313.

Abstract

Marsupials give birth to immunologically naïve young after a relatively short gestation period compared with eutherians. Consequently, the joey relies significantly on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the S100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet, there are numerous additional research opportunities to pursue, including uncovering novel bioactive components and investigating their modes of action, dynamics, stability and ability to penetrate the gut epithelium to facilitate systemic effects.

Extant and extinct bilby genomes combined with Indigenous knowledge improve conservation of a unique Australian marsupial

Type: Journal article

Reference: Hogg, C.J., Edwards, R.J., Farquharson, K.A. et al. Extant and extinct bilby genomes combined with Indigenous knowledge improve conservation of a unique Australian marsupial. Nat Ecol Evol 8, 1311–1326 (2024). https://doi.org/10.1038/s41559-024-02436-2

Abstract

Ninu (greater bilby, Macrotis lagotis) are desert-dwelling, culturally and ecologically important marsupials. In collaboration with Indigenous rangers and conservation managers, we generated the Ninu chromosome-level genome assembly (3.66 Gbp) and genome sequences for the extinct Yallara (lesser bilby, Macrotis leucura). We developed and tested a scat single-nucleotide polymorphism panel to inform current and future conservation actions, undertake ecological assessments and improve our understanding of Ninu genetic diversity in managed and wild populations. We also assessed the beneficial impact of translocations in the metapopulation (N = 363 Ninu). Resequenced genomes (temperate Ninu, 6; semi-arid Ninu, 6; and Yallara, 4) revealed two major population crashes during global cooling events for both species and differences in Ninu genes involved in anatomical and metabolic pathways. Despite their 45-year captive history, Ninu have fewer long runs of homozygosity than other larger mammals, which may be attributable to their boom–bust life history. Here we investigated the unique Ninu biology using 12 tissue transcriptomes revealing expression of all 115 conserved eutherian chorioallantoic placentation genes in the uterus, an XY1Y2 sex chromosome system and olfactory receptor gene expansions. Together, we demonstrate the holistic value of genomics in improving key conservation actions, understanding unique biological traits and developing tools for Indigenous rangers to monitor remote wild populations.

Characterisation of defensins across the marsupial family tree

Type: Journal Article

Reference: Peel, E., Hogg, C. and Belov, K., 2024. Characterisation of defensins across the marsupial family tree. Developmental & Comparative Immunology, p.105207. https://doi.org/10.1016/j.dci.2024.105207

Abstract

Defensins are antimicrobial peptides involved in innate immunity, and gene number differs amongst eutherian mammals. Few studies have investigated defensins in marsupials, despite their potential involvement in immunological protection of altricial young. Here we use recently sequenced marsupial genomes and transcriptomes to annotate defensins in nine species across the marsupial family tree. We characterised 35 alpha and 286 beta defensins; gene number differed between species, although Dasyuromorphs had the largest repertoire. Defensins were encoded in three gene clusters within the genome, syntenic to eutherians, and were expressed in the pouch and mammary gland. Marsupial beta defensins were closely related to eutherians, however marsupial alpha defensins were more divergent. We identified marsupial orthologs of human DEFB3 and 6, and several marsupial-specific beta defensin lineages which may have novel functions. Marsupial predicted mature peptides were highly variable in length and sequence composition. We propose candidate peptides for future testing to elucidate the function of marsupial defensins.

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

Type: Journal Article

Reference: Tang, S., Peel, E., Belov, K., Hogg, C. J., & Farquharson, K. A. (2024). Multi-omics resources for the Australian southern stuttering frog (Mixophyes australis) reveal assorted antimicrobial peptides. Scientific Reports, 14(1), 3991. https://doi.org/10.1038/s41598-024-54522-x

Abstract

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 β-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 β-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.

Emma Peel

Peel, E. J. (2018). Peptides from the Pouch: Marsupial and Monotreme Cathelicidins. The University of Sydney.

The rise in antimicrobial resistance and paucity of new antimicrobial compounds calls for alternatives to traditional antibiotics. Antimicrobial peptides (AMPs) have emerged as potential candidates. Cathelicidins are a major family of AMPs in mammals which form part of innate immunity through antimicrobial and immunomodulatory functions. Marsupial and monotreme cathelicidins are of particular interest due to their involvement in protecting immunologically naive young during development in the pouch via expression in the pouch lining and milk where they modulate microbial flora and provide passive immunity. As such, the cathelicidin gene family has expanded in marsupials and monotremes, with a high number of cathelicidins in the tammar wallaby, gray short-tailed opossum and platypus. However our knowledge is limited to these species and functional studies involving antimicrobial activity are lacking. This thesis describes the characterisation of cathelicidins in the Tasmanian devil, koala and echidna, and investigates the antimicrobial function of all marsupial and monotreme cathelicidins. As expected, cathelicidins have expanded in the Tasmanian devil and koala, resulting in a high number of cathelicidins which were widely expressed throughout the body, including in pouch lining and milk. Only a single cathelicidin was identified in the echidna due to the quality of the genome. Out of 26 cathelicidins tested, six displayed broad-spectrum antibacterial activity against gram-negative and positive bacteria, including methicillin-resistant Staphylococcus aureus. One koala cathelicidin rapidly inactivated C. pecorum and significantly reduced the number of chlamydial inclusions in vitro. Activity was reduced in the presence of serum and whole blood, and peptides displayed varying levels of haemolytic and cytotoxic activity. Many cathelicidins did not display antimicrobial activity and future work is required to explore their potential immunomodulatory properties. The results presented in this thesis have advanced our understanding of cathelicidins in marsupials and monotremes on a genetic and functional level, and highlights their potential as novel therapeutics in the future.

https://sydney.primo.exlibrisgroup.com/permalink/61USYD_INST/1c0ug48/alma991032033232205106

The Sydney Morning Herold: Devil’s milk could be the killer ingredient in war on superbugs

PhD candidate Emma Peel from the School of Life and Environmental Sciences was interviewed about new research that has proved Tasmanian Devil’s milk can kill some of the most deadly bacterial and fungal infections

Read the full article here: https://www.smh.com.au/technology/devils-milk-could-be-the-killer-ingredient-in-war-on-superbugs-20161014-gs29l5.html