School of BioSciences - Research Publications

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    Editorial: Fetal testicular hormones.
    Josso, N ; Rey, RA ; Pask, A (Frontiers Media SA, 2022)
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    Widespread cis-regulatory convergence between the extinct Tasmanian tiger and gray wolf
    Feigin, CY ; Newton, AH ; Pask, AJ (COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT, 2019-10)
    The extinct marsupial Tasmanian tiger, or thylacine, and the eutherian gray wolf are among the most widely recognized examples of convergent evolution in mammals. Despite being distantly related, these large predators independently evolved extremely similar craniofacial morphologies, and evidence suggests that they filled similar ecological niches. Previous analyses revealed little evidence of adaptive convergence between their protein-coding genes. Thus, the genetic basis of their convergence is still unclear. Here, we identified candidate craniofacial cis-regulatory elements across vertebrates and compared their evolutionary rates in the thylacine and wolf, revealing abundant signatures of convergent positive selection. Craniofacial thylacine-wolf accelerated regions were enriched near genes involved in TGF beta (TGFB) and BMP signaling, both of which are key morphological signaling pathways with critical roles in establishing the identities and boundaries between craniofacial tissues. Similarly, enhancers of genes involved in craniofacial nerve development showed convergent selection and involvement in these pathways. Taken together, these results suggest that adaptation in cis-regulators of TGF beta and BMP signaling may provide a mechanism to explain the coevolution of developmentally and functionally integrated craniofacial structures in these species. We also found that despite major structural differences in marsupial and eutherian brains, accelerated regions in both species were common near genes with roles in brain development. Our findings support the hypothesis that, relative to protein-coding genes, positive selection on cis-regulatory elements is likely to be an essential driver of adaptive convergent evolution and may underpin thylacine-wolf phenotypic similarities.
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    A Chromosome-Scale Hybrid Genome Assembly of the Extinct Tasmanian Tiger (Thylacinus cynocephalus)
    Feigin, C ; Frankenberg, S ; Pask, A ; Fraser, B (OXFORD UNIV PRESS, 2022-04-10)
    The extinct Tasmanian tiger or thylacine (Thylacinus cynocephalus) was a large marsupial carnivore native to Australia. Once ranging across parts of the mainland, the species remained only on the island of Tasmania by the time of European colonization. It was driven to extinction in the early 20th century and is an emblem of native species loss in Australia. The thylacine was a striking example of convergent evolution with placental canids, with which it shared a similar skull morphology. Consequently, it has been the subject of extensive study. While the original thylacine assemblies published in 2018 enabled the first exploration of the species' genome biology, further progress is hindered by the lack of high-quality genomic resources. Here, we present a new chromosome-scale hybrid genome assembly for the thylacine, which compares favorably with many recent de novo marsupial genomes. In addition, we provide homology-based gene annotations, characterize the repeat content of the thylacine genome, and show that consistent with demographic decline, the species possessed a low rate of heterozygosity even compared to extant, threatened marsupials.
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    Strategies for meiotic sex chromosome dynamics and telomeric elongation in Marsupials
    Marin-Gual, L ; Gonzalez-Rodelas, L ; Pujol, G ; Vara, C ; Martin-Ruiz, M ; Berrios, S ; Fernandez-Donoso, R ; Pask, A ; Renfree, MB ; Page, J ; Waters, PD ; Ruiz-Herrera, A ; Copenhaver, GP (PUBLIC LIBRARY SCIENCE, 2022-02)
    During meiotic prophase I, homologous chromosomes pair, synapse and recombine in a tightly regulated process that ensures the generation of genetically variable haploid gametes. Although the mechanisms underlying meiotic cell division have been well studied in model species, our understanding of the dynamics of meiotic prophase I in non-traditional model mammals remains in its infancy. Here, we reveal key meiotic features in previously uncharacterised marsupial species (the tammar wallaby and the fat-tailed dunnart), plus the fat-tailed mouse opossum, with a focus on sex chromosome pairing strategies, recombination and meiotic telomere homeostasis. We uncovered differences between phylogroups with important functional and evolutionary implications. First, sex chromosomes, which lack a pseudo-autosomal region in marsupials, had species specific pairing and silencing strategies, with implications for sex chromosome evolution. Second, we detected two waves of γH2AX accumulation during prophase I. The first wave was accompanied by low γH2AX levels on autosomes, which correlated with the low recombination rates that distinguish marsupials from eutherian mammals. In the second wave, γH2AX was restricted to sex chromosomes in all three species, which correlated with transcription from the X in tammar wallaby. This suggests non-canonical functions of γH2AX on meiotic sex chromosomes. Finally, we uncover evidence for telomere elongation in primary spermatocytes of the fat-tailed dunnart, a unique strategy within mammals. Our results provide new insights into meiotic progression and telomere homeostasis in marsupials, highlighting the importance of capturing the diversity of meiotic strategies within mammals.
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    Oestrogen Activates the MAP3K1 Cascade and β-Catenin to Promote Granulosa-like Cell Fate in a Human Testis-Derived Cell Line
    Stewart, MK ; Bernard, P ; Ang, C-S ; Mattiske, DM ; Pask, AJ (MDPI, 2021-09)
    Sex determination triggers the differentiation of the bi-potential gonad into either an ovary or testis. In non-mammalian vertebrates, the presence or absence of oestrogen dictates gonad differentiation, while in mammals, this mechanism has been supplanted by the testis-determining gene SRY. Exogenous oestrogen can override this genetic trigger to shift somatic cell fate in the gonad towards ovarian developmental pathways by limiting the bioavailability of the key testis factor SOX9 within somatic cells. Our previous work has implicated the MAPK pathway in mediating the rapid cellular response to oestrogen. We performed proteomic and phosphoproteomic analyses to investigate the precise mechanism through which oestrogen impacts these pathways to activate β-catenin-a factor essential for ovarian development. We show that oestrogen can activate β-catenin within 30 min, concomitant with the cytoplasmic retention of SOX9. This occurs through changes to the MAP3K1 cascade, suggesting this pathway is a mechanism through which oestrogen influences gonad somatic cell fate. We demonstrate that oestrogen can promote the shift from SOX9 pro-testis activity to β-catenin pro-ovary activity through activation of MAP3K1. Our findings define a previously unknown mechanism through which oestrogen can promote a switch in gonad somatic cell fate and provided novel insights into the impacts of exogenous oestrogen exposure on the testis.
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    Postnatal development in a marsupial model, the fat-tailed dunnart (Sminthopsis crassicaudata; Dasyuromorphia: Dasyuridae)
    Cook, LE ; Newton, AH ; Hipsley, CA ; Pask, AJ (NATURE PORTFOLIO, 2021-09-02)
    Marsupials exhibit unique biological features that provide fascinating insights into many aspects of mammalian development. These include their distinctive mode of reproduction, altricial stage at birth, and the associated heterochrony that is required for their crawl to the pouch and teat attachment. Marsupials are also an invaluable resource for mammalian comparative biology, forming a distinct lineage from the extant placental and egg-laying monotreme mammals. Despite their unique biology, marsupial resources are lagging behind those available for placentals. The fat-tailed dunnart (Sminthopsis crassicaudata) is a laboratory based marsupial model, with simple and robust husbandry requirements and a short reproductive cycle making it amenable to experimental manipulations. Here we present a detailed staging series for the fat-tailed dunnart, focusing on their accelerated development of the forelimbs and jaws. This study provides the first skeletal developmental series on S. crassicaudata and provides a fundamental resource for future studies exploring mammalian diversification, development and evolution.
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    Endocrine disrupting chemicals in the pathogenesis of hypospadias; developmental and toxicological perspectives
    Mattiske, DM ; Pask, AJ (ELSEVIER, 2021)
    Hypospadias is a defect in penile urethral closure that occurs in approximately 1/150 live male births in developed nations, making it one of the most common congenital abnormalities worldwide. Alarmingly, the frequency of hypospadias has increased rapidly over recent decades and is continuing to rise. Recent research reviewed herein suggests that the rise in hypospadias rates can be directly linked to our increasing exposure to endocrine disrupting chemicals (EDCs), especially those that affect estrogen and androgen signalling. Understanding the mechanistic links between endocrine disruptors and hypospadias requires toxicologists and developmental biologists to define exposures and biological impacts on penis development. In this review we examine recent insights from toxicological, developmental and epidemiological studies on the hormonal control of normal penis development and describe the rationale and evidence for EDC exposures that impact these pathways to cause hypospadias. Continued collaboration across these fields is imperative to understand the full impact of endocrine disrupting chemicals on the increasing rates of hypospadias.
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    Atrazine induces penis abnormalities including hypospadias in mice
    Govers, LC ; Harper, AP ; Finger, BJ ; Mattiske, DM ; Pask, AJ ; Green, MP (CAMBRIDGE UNIV PRESS, 2020-06)
    Use of the herbicide atrazine (ATR) is banned in the European Union; yet, it is still widely used in the USA and Australia. ATR is known to alter testosterone and oestrogen production and thus reproductive characteristics in numerous species. In this proof of concept study, we examined the effect of ATR exposure, at a supra-environmental dose (5 mg/kg bw/day), beginning on E9.5 in utero, prior to sexual differentiation of the reproductive tissues, until 26 weeks of age, on the development of the mouse penis. Notably, this is the first study to specifically investigate whether ATR can affect penis characteristics. We show that ATR exposure, beginning in utero, causes a shortening (demasculinisation) of penis structures and increases the incidence of hypospadias in mice. These data indicate the need for further studies of ATR on human reproductive development and fertility, especially considering its continued and widespread use.
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    Evolution and expansion of the RUNX2 QA repeat corresponds with the emergence of vertebrate complexity (vol 3, 771, 2020)
    Newton, AH ; Pask, AJ (NATURE RESEARCH, 2021-01-25)
    A Correction to this paper has been published: https://doi.org/10.1038/s42003-021-01687-0.
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    Ontogenetic origins of cranial convergence between the extinct marsupial thylacine and placental gray wolf
    Newton, AH ; Weisbecker, V ; Pask, AJ ; Hipsley, CA (NATURE PORTFOLIO, 2021-01-08)
    Phenotypic convergence, describing the independent evolution of similar characteristics, offers unique insights into how natural selection influences developmental and molecular processes to generate shared adaptations. The extinct marsupial thylacine and placental gray wolf represent one of the most extraordinary cases of convergent evolution in mammals, sharing striking cranial similarities despite 160 million years of independent evolution. We digitally reconstructed their cranial ontogeny from birth to adulthood to examine how and when convergence arises through patterns of allometry, mosaicism, modularity, and integration. We find the thylacine and wolf crania develop along nearly parallel growth trajectories, despite lineage-specific constraints and heterochrony in timing of ossification. These constraints were found to enforce distinct cranial modularity and integration patterns during development, which were unable to explain their adult convergence. Instead, we identify a developmental origin for their convergent cranial morphologies through patterns of mosaic evolution, occurring within bone groups sharing conserved embryonic tissue origins. Interestingly, these patterns are accompanied by homoplasy in gene regulatory networks associated with neural crest cells, critical for skull patterning. Together, our findings establish empirical links between adaptive phenotypic and genotypic convergence and provides a digital resource for further investigations into the developmental basis of mammalian evolution.