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Feigin, C. Y.

Publications and source records attributed to Feigin, C. Y..

9 recordsLinked to original sources

Genomes of two arid-zone marsupials uncover contrasting responses to climatic change

Small marsupials in the family Dasyuridae are a key component of Australias arid and semi-arid fauna, whose high species richness is proposed to reflect an opportunity-driven adaptive radiation. Despite growing interest in this group from both ecological and evolutionary perspectives, genomic data for most species is non-existent, or limited to a few marker loci. Here, we generated a chromosome-level reference genome and a de novo mitochondrial genome for the desert-dwelling Wongai ningaui (Ningaui ridei). The nuclear genome assembly is highly contiguous, with a scaffold N50 of 594.5 MB and high BUSCO gene recovery (93.8%). Additionally, we produced a draft assembly for the related, semi-arid slender-tailed dunnart (Sminthopsis murina). We then used these assemblies to explore the demographic histories of these species. We find evidence for contrasting patterns of population growth during the late Pleistocene and early Holocene, corresponding with differences in local climate, potentially consistent with differences in optimal habitat. The new genomic resources and demographic findings presented here provide a foundation for future studies on adaptive specialisation in this group of Australian marsupials. Significance StatementDasyurid marsupials are the primary carnivorous and insectivorous mammals in Australia. This family includes species such as the endangered Tasmanian devil (Sarcophilus harrisii) and quolls (Genus Dasyurus), as well as an emerging model species, the fat-tailed dunnart (Sminthopsis crassicaudata). Despite the species richness within dasyurids, most species remain under-studied. This is particularly true of arid and semi-arid zone species, who are often small in size, live in remote habitats and are cryptic by nature. By creating genome assemblies for two dasyurid species, this study provides resources to support phylogenetic, comparative and conservation research in arid zone marsupials. Importantly, the studys finding that arid and semi-arid species show distinct trajectories of demographic change in response to historical climate may have implications for the resilience of locally-adapted dasyurid species to ongoing climate change.

genomics↗

Loss-of-function mutations in ASIP and MC1R are associated with coat color variation in marsupials.

Pigment production in mammalian hair follicles is governed in part by interactions between Agouti Signalling Protein (ASIP) and the Melanocortin 1 Receptor (MC1R). The most common coat colours in mammals result from alternating bands of dark eumelanin and light pheomelanin within individual hairs. However, coats dominated by a single type of melanin have arisen several times. Here, we examine the genetic basis of two instances among the marsupials: a melanistic morph of the eastern quoll (Dasyurus viverrinus) found at high frequency in the wild, and a rare case of fixed xanthism in the marsupial moles. In the eastern quoll, we show that a deletion encompassing part of the ASIP coding sequence likely explains melanism in this species. Notably, this mutation is convergent with that recently discovered in its dark-coated relative, the Tasmanian devil (Sarcophilus harrisii). Conversely, we show that a nonsense mutation which severely truncates MC1R in the southern marsupial mole (Notoryctes typhlops) is a strong candidate driver of its pheomelanin-predominant coat. Together with other recent findings, our results suggest that loss-of-function mutations have occurred repeatedly within the marsupials, representing an important mechanism underpinning coat colour variation.

genomics↗

Cathelicidin antimicrobial peptides mediate immune protection of marsupial neonates

Marsupial neonates are born with immature immune systems, making them vulnerable to pathogens. While neonates receive maternal protection, they can also independently combat pathogens, though the mechanisms remain unknown. Using the sugar glider (Petaurus breviceps) as a model, we investigated immunological defense strategies of marsupial neonates. Cathelicidins - a family of antimicrobial peptides expanded in the genomes of marsupials - are highly expressed in developing neutrophils. Sugar glider cathelicidins reside in two genomic clusters and their coordinated expression is achieved by enhancer sharing within clusters and long-range physical interactions between clusters. These cathelicidins modulate immune responses and have potent antimicrobial effects, sufficient to provide protection in a mouse model of sepsis. Lastly, cathelicidins have a complex evolutionary history, where marsupials and monotremes are the only tetrapods that retained two cathelicidin clusters. Thus, cathelicidins are critical mediators of marsupial immunity, and their evolution reflects the life history-specific immunological needs of these animals.

evolutionary biology↗

De novo transcriptome assembly and genome annotation of the fat-tailed dunnart (Sminthopsis crassicaudata)

Marsupials exhibit highly specialized patterns of reproduction and development, making them uniquely valuable for comparative genomics studies with their sister lineage, eutherian (also known as placental) mammals. However, marsupial genomic resources still lag far behind those of eutherian mammals, limiting our insight into mammalian diversity. Here, we present a series of novel genomic resources for the fat-tailed dunnart (Sminthopsis crassicaudata), a mouse-like marsupial that, due to its ease of husbandry and ex-utero development, is emerging as a laboratory model. To enable wider use, we have generated a multi-tissue de novo transcriptome assembly of dunnart RNA-seq reads spanning 12 tissues. This highly representative transcriptome is comprised of 2,093,982 assembled transcripts, with a mean transcript length of 830 bp. The transcriptome mammalian BUSCO completeness score of 93% is the highest amongst all other published marsupial transcriptomes. Additionally, we report an improved fat-tailed dunnart genome assembly which is 3.23 Gb long, organized into 1,848 scaffolds, with a scaffold N50 of 72.64 Mb. The genome annotation, supported by assembled transcripts and ab initio predictions, revealed 21,622 protein-coding genes. Altogether, these resources will contribute greatly towards characterizing marsupial biology and mammalian genome evolution.

genomics↗

Reference genome of the endangered eastern quoll (Dasyurus viverrinus)

The eastern quoll (Dasyurus viverrinus) is an endangered marsupial mesopredator native to Australia. Since the extirpation of the last mainland Australian populations in the late 20th century, wild populations of this species have been restricted to two islands at the far southern end of its historical range. Eastern quolls are the subject of captive breeding programs and attempts have recently been made to re-establish a population in mainland Australia through translocations. However, few resources currently exist to guide the genetic management of this species. Here, we generated a chromosome-scale reference genome for the eastern quoll, along with gene annotations supported by multi-tissue transcriptomes. Through comparisons with related species, we find that our reference genome is among the most complete marsupial assemblies currently available. Using this assembly, we infer the species demographic history and identify potential evidence of a long-term decline beginning in the late Pleistocene. Finally, we identify a deletion at the ASIP locus that likely drives differences in pelage color between the eastern quoll and the closely related Tasmanian devil (Sarcophilus harrisii). The genomic resources we present are valuable new tools for evolutionary and conservation genomic studies.

genomics↗

Cis-regulatory landscapes of the fat-tailed dunnart and mouse provide insights into the drivers of craniofacial heterochrony

Marsupials and placental mammals exhibit significant differences in reproductive and life history strategies. Marsupials are born highly underdeveloped after an extremely short period of gestation, leading to prioritization of the development of structures critical for post-birth survival in the pouch. Critically, they must undergo accelerated development of the oro-facial region compared to placentals. Previously we described the accelerated development of the oro-facial region in the carnivorous Australian marsupial, the fat-tailed dunnart Sminthopsis crassicaudata that has one of the shortest gestations of any mammal. By combining genome comparisons of the mouse and dunnart with functional data for the enhancer-associated chromatin modifications, H3K4me3 and H3K27ac, we investigated divergence of craniofacial regulatory landscapes between these species. This is the first description of genome-wide face regulatory elements in a marsupial, with 60,626 putative enhancers and 12,295 putative promoters described. We also generated craniofacial RNA-seq data for the dunnart to investigate expression dynamics of genes near predicted active regulatory elements. While genes involved in regulating facial development were largely conserved in mouse and dunnart, the regulatory landscape varied significantly. Additionally, a subset of dunnart-specific enhancers were associated with genes highly expressed only in dunnart relating to cranial neural crest proliferation, embryonic myogenesis and epidermis development. Comparative RNA-seq analyses of facial tissue revealed dunnart-specific expression of genes involved in the development of the mechanosensory system. Accelerated development of the dunnart sensory system likely relates to the sensory cues received by the nasal-oral region during the postnatal journey to the pouch. Together these data suggest that accelerated face development in the dunnart may be driven by dunnart-specific enhancer activity. Our study highlights the power of marsupial-placental comparative genomics for understanding the role of enhancers in driving temporal shifts in development.

developmental biology↗

Sfrp2 is a multifunctional regulator of rodent color patterns

Animal pigment patterns are excellent models to elucidate mechanisms of biological organization. Although theoretical simulations, such as Turing reaction-diffusion systems, recapitulate many animal patterns, they are insufficient to account for those showing a high degree of spatial organization and reproducibility. Here, we compare the coats of the African striped mouse (Rhabdomys pumilio) and the laboratory mouse (Mus musculus) to study the molecular mechanisms controlling stripe pattern formation. By combining transcriptomics, mathematical modeling, and mouse transgenics, we show that Sfrp2 regulates the distribution of hair follicles and establishes an embryonic prepattern that foreshadows pigment stripes. Moreover, by developing and employing in vivo gene editing experiments in striped mice, we find that Sfrp2 knockout is sufficient to alter the stripe pattern. Strikingly, mutants also exhibit changes in coat color, revealing an additional function of Sfrp2 in regulating hair color. Thus, a single factor controls coat pattern formation by acting both as an orienting signaling mechanism and a modulator of pigmentation. By uncovering a multifunctional regulator of stripe formation, our work provides insights into the mechanisms by which spatial patterns are established in developing embryos and the molecular basis of phenotypic novelty.

developmental biology↗

Convergent deployment of ancestral programs during the evolution of mammalian flight membranes

Lateral flight membranes, or patagia, have evolved repeatedly in diverse mammalian lineages. While little is known about patagium development, its recurrent evolution may suggest a shared molecular basis. By combining transcriptomics, developmental experiments, and mouse transgenics, we demonstrate that lateral WNT5A expression in the marsupial sugar glider (Petaurus breviceps) promotes the differentiation of its patagium primordium. We further show that this function of WNT5A reprises ancestral roles in skin morphogenesis predating mammalian flight and has been convergently employed during patagium evolution in eutherian bats. Moreover, we find that many genes involved in limb development have been re-deployed during patagium outgrowth in both the sugar glider and bat. Taken together, our findings reveal that deeply conserved molecular toolkits underpin the evolutionary transition to flight in mammals.

developmental biology↗

A chromosome-scale hybrid genome assembly of the extinct Tasmanian tiger (Thylacinus cynocephalus)

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. Additionally, 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. SignificanceThe lack of high-quality genomes for extinct species inhibits research into their biology. Moreover, marsupials are underrepresented among sequenced genomes. Here, we present a new, chromosome-scale thylacine genome. This high-quality assembly is a valuable new resource for studies on marsupial carnivores.

genomics↗