The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Frank Grützner - One of the best experts on this subject based on the ideXlab platform.
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Monotreme glucagon-like peptide-1 in venom and gut: one gene – two very different functions
Scientific Reports, 2016Co-Authors: Enkhjargal Tsend-ayush, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank GrütznerAbstract:The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of Monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that Monotremes evolved an alternative mechanism to degrade GLP-1. We also show that Monotreme GLP-1 stimulates insulin release in cultured rodent islets, but surprisingly shows low receptor affinity and bias toward Erk signaling. We propose that these changes in Monotreme GLP-1 are the result of conflicting function of this peptide in metabolic control and venom. This evolutionary path is fundamentally different from the generally accepted idea that conflicting functions in a single gene favour duplication and diversification, as is the case for Exendin-4 in gila monster. This provides novel insight into the remarkably different metabolic control mechanism and venom function in Monotremes and an unique example of how different selective pressures act upon a single gene in the absence of gene duplication.
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Monotreme glucagon like peptide 1 in venom and gut one gene two very different functions
Scientific Reports, 2016Co-Authors: Enkhjargal Tsendayush, Mark A. Myers, Sof Andrikopoulos, Nicole Wong, Patrick M. Sexton, Denise Wootten, Briony E. Forbes, Frank GrütznerAbstract:The importance of Glucagon like peptide 1 (GLP-1) for metabolic control and insulin release sparked the evolution of genes mimicking GLP-1 action in venomous species (e.g. Exendin-4 in Heloderma suspectum (gila monster)). We discovered that platypus and echidna express a single GLP-1 peptide in both intestine and venom. Specific changes in GLP-1 of Monotreme mammals result in resistance to DPP-4 cleavage which is also observed in the GLP-1 like Exendin-4 expressed in Heloderma venom. Remarkably we discovered that Monotremes evolved an alternative mechanism to degrade GLP-1. We also show that Monotreme GLP-1 stimulates insulin release in cultured rodent islets, but surprisingly shows low receptor affinity and bias toward Erk signaling. We propose that these changes in Monotreme GLP-1 are the result of conflicting function of this peptide in metabolic control and venom. This evolutionary path is fundamentally different from the generally accepted idea that conflicting functions in a single gene favour duplication and diversification, as is the case for Exendin-4 in gila monster. This provides novel insight into the remarkably different metabolic control mechanism and venom function in Monotremes and an unique example of how different selective pressures act upon a single gene in the absence of gene duplication.
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immunohistochemical analysis of pancreatic islets of platypus ornithorhynchus anatinus and echidna tachyglossus aculeatus ssp
Journal of Anatomy, 2015Co-Authors: Mark A. Myers, Briony E. Forbes, Frank GrütznerAbstract:Monotremes have undergone remarkable changes to their digestive and metabolic control system; however, the Monotreme pancreas remains poorly characterized. Previous work in echidna demonstrated the presence of pancreatic islets, but no information is available for platypus and the fine structure has not been described for either Monotreme. Based on our recent finding that Monotremes lack the ghrelin gene, which is expressed in mouse and human pancreatic islets, we investigated the structure of Monotreme islets in more detail. Generally, as in birds, the islets of Monotremes were smaller but greater in number compared with mouse. β-cells were the most abundant endocrine cell population in platypus islets and were located peripherally, while α-cells were observed both in the interior and periphery of the islets. δ-cells and pancreatic polypeptide (PP)-cells were mainly found in the islet periphery. Distinct PP-rich (PP-lobe) and PP-poor areas (non-PP-lobe) are present in therian mammals, and we identified these areas in echidna but not platypus pancreas. Interestingly, in some of the echidna islets, α- and β-cells tended to form two poles within the islets, which to our knowledge is the first time this has been observed in any species. Overall, Monotreme pancreata share the feature of consisting of distinct PP-poor and PP-rich islets with other mammals. A higher number of islets and α- or β-cell only islets are shared between Monotremes and birds. The islets of Monotremes were larger than those of birds but smaller compared with therian mammals. This may indicate a trend of having fewer larger islets comprising several endocrine cell types during mammalian evolution.
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A PROPOSAL TO SEQUENCE THE GENOME OF THE PLATYPUS, ORNITHORHYNCHUS ANATINUS.
2015Co-Authors: Frank Grützner, Marilyn B. Renfree, Katherine Belov, Janine Deakin, Robert Miller, Y Jirtle, Kerstin Lindblad-toh, Eric S. L, Richard K. WilsonAbstract:The discovery of the egg-laying Monotremes platypus and echidna in Australia more than 200 years ago caused great excitement and controversy in the zoological world. Their combination of reptilian, mammalian and unique characteristics seemed incongruous to 19th century scientists; and because of its strange and unique amalgam of characters, the platypus was initially thought to be a skilled taxidermist’s hoax. However, Monotremes were immediately identified as mammals because they bear fur and feed their young with milk. The evolutionary status of Monotremes, either at the root of mammals or as offshoot of the marsupial lineage, remains controversial today although most Monotreme biologists agree that the Prototherians (the Monotremes) diverged before the Therian (marsupial and eutherian) mammals. Platypus has been the subject of extensive anatomical and physiological studies because of its extraordinary features, including reproduction and development, neuroanatomy and special senses, as well as production (uniquely for a mammal) of venom. These studies have provided a considerable foundation of knowledge about this species that provides a solid basis for functional aspects of genomic compariso
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Changes in the ghrelin hormone pathway maybe part of an unusual gastric system in Monotremes
General and comparative endocrinology, 2013Co-Authors: Enkhjargal Tsend-ayush, Mark A. Myers, Briony E. Forbes, Frank GrütznerAbstract:Ghrelin is a growth hormone (GH)-releasing and appetite-regulating peptide predominately released from the stomach. Ghrelin is evolutionarily highly conserved and known to have a wide range of functions including the regulation of metabolism by maintaining an insulin-glucose balance. The peptide is produced as a single proprotein, which is later proteolytically cleaved. Ghrelin exerts its biological function after O-n-octanoylation at residue serine 3, which is catalyzed by ghrelin O-acyl transferase (GOAT) and allows binding to the growth hormone secretagogue receptor (GHS-R 1a). Genes involved in the ghrelin pathway have been identified in a broad range of vertebrate species, however, little is known about this pathway in the basal mammalian lineage of Monotremes (platypus and echidna). Monotremes are particularly interesting in this context, as they have undergone massive changes in stomach anatomy and physiology, accompanied by a striking loss of genes involved in gastric function. In this study, we investigated genes in the ghrelin pathway in Monotremes. Using degenerate PCR, database searches and synteny analysis we found that genes encoding ghrelin and GOAT are missing in the platypus genome, whilst, as has been reported in other species, the GHSR is present and expressed in brain, pancreas, kidney, intestine, heart and stomach. This is the first report suggesting the loss of ghrelin in a mammal. The loss of this gene may be related to changes to the platypus digestive system and raises questions about the control of blood glucose levels and insulin response in Monotreme mammals. In addition, the conservation of the ghrelin receptor gene in platypus indicates that another ligand(s) maybe acting via this receptor in Monotremes.
Ken W.s. Ashwell - One of the best experts on this subject based on the ideXlab platform.
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The Monotreme Nervous System
Evolution of Nervous Systems, 2017Co-Authors: Ken W.s. AshwellAbstract:Monotremes are egg-laying mammals and include the modern platypus and the short- and long-beaked echidnas. The Monotremes occupy a unique place in mammalian brain evolution and diverged in evolutionary history from all other mammals as much as 115 million years, but they should not be seen as evolutionary relics, nor as models of the archaic mammalian brain. The nervous systems of extant Monotremes exhibit specializations such as electroreception that are just as remarkable as those found among the eutherians, and the Monotreme brain is as far removed from the ancestral mammal brain as any other modern mammal.
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development of the hypothalamus and pituitary in platypus ornithorhynchus anatinus and short beaked echidna tachyglossus aculeatus
Journal of Anatomy, 2012Co-Authors: Ken W.s. AshwellAbstract:The living Monotremes (platypus and echidnas) are distinguished by the development of their young in a leathery-shelled egg, a low and variable body temperature and a primitive teat-less mammary gland. Their young are hatched in an immature state and must deal with the external environment, with all its challenges of hypothermia and stress, as well as sourcing nutrients from the maternal mammary gland. The Hill and Hubrecht embryological collections have been used to follow the structural development of the Monotreme hypothalamus and its connections with the pituitary gland both in the period leading up to hatching and during the lactational phase of development, and to relate this structural maturation to behavioural development. In the incubation phase, development of the hypothalamus proceeds from closure of the anterior neuropore to formation of the lateral hypothalamic zone and putative medial forebrain bundle. Some medial zone hypothalamic nuclei are emerging at the time of hatching, but these are poorly differentiated and periventricular zone nuclei do not appear until the first week of post-hatching life. Differentiation of the pituitary is also incomplete at hatching, epithelial cords do not develop in the pars anterior until the first week, and the hypothalamo-neurohypophyseal tract does not appear until the second week of post-hatching life. In many respects, the structure of the hypothalamus and pituitary of the newly hatched Monotreme is similar to that seen in newborn marsupials, suggesting that both groups rely solely on lateral hypothalamic zone nuclei for whatever homeostatic mechanisms they are capable of at birth/hatching.
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development of the cerebellum in the platypus ornithorhynchus anatinus and short beaked echidna tachyglossus aculeatus
Brain Behavior and Evolution, 2012Co-Authors: Ken W.s. AshwellAbstract:The Monotremes are a unique group of mammals whose young are incubated in a leathery-shelled egg and fed with milk from teatless areolae after hatching. As soon as they hatch, Monotreme young must be able to maneuver around the nest or maternal pouch to locate the areolae and stimulate milk ejection. In the present study, the embryological collections at the Museum fur Naturkunde, Berlin, have been used to follow the development of the Monotreme cerebellum through incubation and lactational phases, to determine whether cerebellar circuitry is able to contribute to the coordination of locomotion in the Monotreme hatchling, and to correlate cerebellar development with behavioral maturation. The structure of the developing Monotreme cerebellum and the arrangement of transitory neuronal populations are similar to those reported for fetal and neonatal eutherians, but the time course of the key events of later cerebellar development is spread over a much longer period. Expansion of the rostral rhombic lip and formation of the nuclear and cortical transitory zones occurs by the time of hatching, but it is not until after the end of the first post-hatching week that deep cerebellar neurons begin to settle in their definitive positions and the Purkinje cell layer can be distinguished. Granule cell formation is also prolonged over many post-hatching months and the external granular layer persists for more than 20 weeks after hatching. The findings indicate that cerebellar circuitry is unlikely to contribute to the coordination of movements in the Monotreme peri-hatching period. Those activities are most likely controlled by the spinal cord and medullary reticular formation circuitry.
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distinct development of the cerebral cortex in platypus and echidna
Brain Behavior and Evolution, 2012Co-Authors: Ken W.s. Ashwell, Craig D HardmanAbstract:Both lineages of the modern Monotremes have distinctive features in the cerebral cortex, but the developmental mechanisms that produce such different adult cortical architecture remain unknown. Similarly, nothing is known about the differences and/or similarities between Monotreme and therian cortical development. We have used material from the Hill embryological collection to try to answer key questions concerning cortical development in Monotremes. Our findings indicate that gyrencephaly begins to emerge in the echidna brain shortly before birth (crown-rump length 12.5 mm), whereas the cortex of the platypus remains lissencephalic throughout development. The cortices of both Monotremes are very immature at the time of hatching, much like that seen in marsupials, and both have a subventricular zone (SubV) within both the striatum and pallium during post-hatching development. It is particularly striking that in the platypus, this region has an extension from the palliostriatal angle beneath the developing trigeminoreceptive part of the somatosensory cortex of the lateral cortex. The putative SubV beneath the trigeminal part of S1 appears to accommodate at least two distinct types of cell and many mitotic figures and (particularly in the platypus) appears to be traversed by large numbers of thalamocortical axons as these grow in. The association with putative thalamocortical fibres suggests that this region may also serve functions similar to the subplate zone of Eutheria. These findings suggest that cortical development in each Monotreme follows distinct paths from at least the time of birth, consistent with a long period of independent and divergent cortical evolution.
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Development of the olfactory pathways in platypus and echidna.
Brain behavior and evolution, 2011Co-Authors: Ken W.s. AshwellAbstract:The two groups of living Monotremes (platypus and echidnas) have remarkably different olfactory structures in the adult. The layers of the main olfactory bulb of the short-beaked echidna are extensively folded, whereas those of the platypus are not. Similarly, the surface area of the piriform cortex of the echidna is large and its lamination complex, whereas in the platypus it is small and simple. It has been argued that the modern echidnas are derived from a platypus-like ancestor, in which case the extensive olfactory specializations of the modern echidnas would have developed relatively recently in Monotreme evolution. In this study, the development of the constituent structures of the olfactory pathway was studied in sectioned platypus and echidna embryos and post-hatchlings at the Museum fur Naturkunde, Berlin, Germany. The aim was to determine whether the olfactory structures follow a similar maturational path in the two Monotremes during embryonic and early post-hatching ages or whether they show very different developmental paths from the outset. The findings indicate that anatomical differences in the central olfactory system between the short-beaked echidna and the platypus begin to develop immediately before hatching, although details of differences in nasal cavity architecture emerge progressively during late post-hatching life. These findings are most consistent with the proposition that the two modern Monotreme lineages have followed independent evolutionary paths from a less olfaction-specialized ancestor. The Monotreme olfactory pathway does not appear to be sufficiently structurally mature at birth to allow olfaction-mediated behaviour, because central components of both the main and accessory olfactory system have not differentiated at the time of hatching.
Katherine Belov - One of the best experts on this subject based on the ideXlab platform.
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marsupial and Monotreme cathelicidins display antimicrobial activity including against methicillin resistant staphylococcus aureus
Microbiology, 2017Co-Authors: Emma Peel, Yuanyuan Cheng, Julianne T Djordjevic, Michael Kuhn, Tania C Sorrell, Katherine BelovAbstract:With the growing demand for new antibiotics to combat increasing multi-drug resistance, a family of antimicrobial peptides known as cathelicidins has emerged as potential candidates. Expansions in cathelicidin-encoding genes in marsupials and Monotremes are of specific interest as the peptides they encode have evolved to protect immunologically naive young in the harsh conditions of the pouch and burrow. Our previous work demonstrated that some marsupial and Monotreme cathelicidins have broad-spectrum antibacterial activity and kill resistant bacteria, but the activity of many cathelicidins is unknown. To investigate associations between peptide antimicrobial activity and physiochemical properties, we tested 15 cathelicidin mature peptides from tammar wallaby, grey short-tailed opossum, platypus and echidna for antimicrobial activity against a range of bacterial and fungal clinical isolates. One opossum cathelicidin ModoCath4, tammar wallaby MaeuCath7 and echidna Taac-CATH1 had broad-spectrum antibacterial activity and killed methicillin-resistant Staphylococcus aureus. However, antimicrobial activity was reduced in the presence of serum or whole blood, and non-specific toxicity was observed at high concentrations. The active peptides were highly charged, potentially increasing binding to microbial surfaces, and contained amphipathic helical structures, which may facilitate membrane permeabilisation. Peptide sequence homology, net charge, amphipathicity and alpha helical content did not correlate with antimicrobial activity. However active peptides contained a significantly higher percentage of cationic residues than inactive ones, which may be used to predict active peptides in future work. Along with previous studies, our results indicate that marsupial and Monotreme cathelicidins show potential for development as novel therapeutics to combat increasing antimicrobial resistance.
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Diversity at the Major Histocompatibility Complex Class II in
2016Co-Authors: The Platypus, Ornithorhynchus Anatinus, Mette Lillie, Rachael E. Woodward, Claire E. Sanderson, Mark D. B. Eldridge, Katherine BelovAbstract:The platypus (Ornithorhynchus anatinus) is the sole survivor of a previously widely distributed and diverse lineage of ornithorhynchid Monotremes. Its dependence on healthy water systems imposes an inherent sensitivity to habitat degradation and climate change. Here, we compare genetic diversity at the major histocompatibility complex (MHC) Class II-DZB gene and 3 MHC-associated microsatellite markers with diversity at 6 neutral microsatellite markers in 70 platypuses from across their range, including the mainland of Australia and the isolated populations of Tasmania, King Island, and Kangaroo Island. Overall, high DZB diversity was observed in the platypus, with 57 DZB b1 alleles characterized. Significant positive selection was detected within the DZB peptide-binding region, promoting variation in this domain. Low levels of genetic diversity were detected at all markers in the 2 island populations, King Island (endemic) and Kangaroo Island (introduced), with the King Island platypuses monomorphic at the DZB locus. Loss of MHC diversity on King Island is of concern, as the population may have compromised immunological fitness and reduced ability to resist changing environmental conditions. Key words: island populations, MHC diversity, Monotreme, platypus The platypus (Ornithorhynchus anatinus) is a small semiaquatic Monotreme found in the waterways of eastern Australia a
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The Immune System of Monotremes and Marsupials
Encyclopedia of Immunobiology, 2016Co-Authors: Emma Peel, Katherine BelovAbstract:Marsupials and Monotremes are two lineages of mammals that have characteristically short gestation periods and give birth to immunologically naive young. These and other unique reproductive characteristics separate them from eutherian mammals. While originally thought to be ‘primitive,’ marsupials and Monotremes have all cells and receptors required for a functioning immune system, including immune tissues, T and B cells, immunoglobulins, cytokines, and antigen receptors. Research in this field has progressed slowly due to the lack of species-specific reagents. However the increased availability of genome sequencing technology in the past decade has enabled in-depth analysis of marsupial and Monotreme immunology. In addition, comparison across mammals has revealed insights into the evolution of the mammalian immune system.
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A PROPOSAL TO SEQUENCE THE GENOME OF THE PLATYPUS, ORNITHORHYNCHUS ANATINUS.
2015Co-Authors: Frank Grützner, Marilyn B. Renfree, Katherine Belov, Janine Deakin, Robert Miller, Y Jirtle, Kerstin Lindblad-toh, Eric S. L, Richard K. WilsonAbstract:The discovery of the egg-laying Monotremes platypus and echidna in Australia more than 200 years ago caused great excitement and controversy in the zoological world. Their combination of reptilian, mammalian and unique characteristics seemed incongruous to 19th century scientists; and because of its strange and unique amalgam of characters, the platypus was initially thought to be a skilled taxidermist’s hoax. However, Monotremes were immediately identified as mammals because they bear fur and feed their young with milk. The evolutionary status of Monotremes, either at the root of mammals or as offshoot of the marsupial lineage, remains controversial today although most Monotreme biologists agree that the Prototherians (the Monotremes) diverged before the Therian (marsupial and eutherian) mammals. Platypus has been the subject of extensive anatomical and physiological studies because of its extraordinary features, including reproduction and development, neuroanatomy and special senses, as well as production (uniquely for a mammal) of venom. These studies have provided a considerable foundation of knowledge about this species that provides a solid basis for functional aspects of genomic compariso
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Tracing Monotreme Venom Evolution in the Genomics Era
Toxins, 2014Co-Authors: Camilla M. Whittington, Katherine BelovAbstract:The Monotremes (platypuses and echidnas) represent one of only four extant venomous mammalian lineages. Until recently, Monotreme venom was poorly understood. However, the availability of the platypus genome and increasingly sophisticated genomic tools has allowed us to characterize platypus toxins, and provides a means of reconstructing the evolutionary history of Monotreme venom. Here we review the physiology of platypus and echidna crural (venom) systems as well as pharmacological and genomic studies of Monotreme toxins. Further, we synthesize current ideas about the evolution of the venom system, which in the platypus is likely to have been retained from a venomous ancestor, whilst being lost in the echidnas. We also outline several research directions and outstanding questions that would be productive to address in future research. An improved characterization of mammalian venoms will not only yield new toxins with potential therapeutic uses, but will also aid in our understanding of the way that this unusual trait evolves.
Lars Hellman - One of the best experts on this subject based on the ideXlab platform.
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The complexity of expressed kappa light chains in egg-laying mammals
Immunogenetics, 2004Co-Authors: Melissa A. Nowak, Zuly E. Parra, Lars Hellman, Robert D. MillerAbstract:Complementary DNAs encoding immunoglobulin light chains were isolated from two Monotreme species, Ornithorhynchus anatinus (duckbill platypus) and Tachyglossus aculeatus (echidna). The sequences of both the variable and constant regions of these clones had greater similarity to IGK than to other light chain classes and phylogenetic analyses place them squarely within the mammalian IGK group, establishing them as Monotreme IGK homologues. The constant region sequences of all clones were essentially identical within each species and, along with Southern blot results, the data are consistent with a single IGKC in each species. The expressed IGKV repertoires from both platypus and echidna were randomly sampled and there appear to be at least four platypus and at least nine echidna IGKV subgroups. The IGKV subgroups are highly divergent within species, in some cases sharing as little as 57% nucleotide identity. Two of the IGKV subgroups are present in both species, so there is some degree of overlap in the germline repertoires of these two Monotremes. Overall the complexity seen in platypus and echidna IGK light chains is comparable with that of other mammals considered to have high levels of germline diversity and is in contrast to what has been found so far for Monotreme IGL .
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cloning of ige from the echidna tachyglossus aculeatus and a comparative analysis of e chains from all three extant mammalian lineages
Developmental and Comparative Immunology, 2004Co-Authors: Molly Vernersson, Maria Aveskogh, Lars HellmanAbstract:In continuation of our evolutionary studies of immunoglobulin (Ig) expression, we present here the cloning of IgE from a Monotreme, the short-beaked echidna (Tachyglossus aculeatus). Including echidna IgE, 15 epsilon chain sequences have been isolated and each of the three mammalian lineages (placentals, marsupials and Monotremes) is now represented by at least two sequences. Phylogenetic analyses based on all available epsilon chains and a selection of other mammalian Ig isotypes (IgM, IgA and IgG) were generated using three different algorithms. The resulting trees strongly support the Theria hypothesis, which states that the Monotreme lineage was the first of the three extant mammalian lineages to appear in evolution. Furthermore, to increase our understanding of IgE we have done a detailed comparative analysis, with focus on primary structure, potential N-glycosylation, charge distribution and conservation of residues in the putative receptor-binding site. The overall structure of IgE, i.e. four constant domains and the positions of putative disulfide-bridge formations, are conserved, as is an N-glycosylation site in the third constant domain. An increased homology was observed in the putative receptor-binding site, which suggests an important function for the IgE/Fc epsilon RI interaction. IgE has been found exclusively in mammals, but it is present in all extant mammalian lineages. This, together with the overall conservation of structure, indicates that IgE appeared as a separate isotype early in mammalian evolution and that structural maintenance may have a selective advantage.
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immunoglobulin genetics of ornithorhynchus anatinus platypus and tachyglossus aculeatus short beaked echidna
Comparative Biochemistry and Physiology A-molecular & Integrative Physiology, 2003Co-Authors: Katherine Belov, Lars HellmanAbstract:In this paper, we review data on the Monotreme immune system focusing on the characterisation of lymphoid tissue and of antibody responses, as well the recent cloning of immunoglobulin genes. It is now known that Monotremes utilise immunoglobulin isotypes that are structurally identical to those found in marsupials and eutherians, but which differ to those found in birds and reptiles. Monotremes utilise IgM, IgG, IgA and IgE. They do not use IgY. Their IgG and IgA constant regions contain three domains plus a hinge region. Preliminary analysis of Monotreme heavy chain variable region diversity suggests that the platypus primarily uses a single VH clan, while the short-beaked echidna utilises at least 4 distinct VH families which segregate into all three mammalian VH clans. Phylogenetic analysis of the immunoglobulin heavy chain constant region gene sequences provides strong support for the Theria hypothesis. The constant region of IgM has proven to be a useful marker for estimating the time of divergence of mammalian lineages.
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evolution of the major histocompatibility complex isolation of class ii β cdnas from two Monotremes the platypus and the short beaked echidna
Immunogenetics, 2003Co-Authors: Katherine Belov, Lars Hellman, Mary K Lam, D J ColganAbstract:Extant mammals are composed of three lineages: the eutherians, the marsupials and the Monotremes. The majority of the mammalian major histocompatibility complex (MHC) data is based on the eutherian mammals, which generally have three classical MHC class II β chain gene clusters — DRB, DQB and DPB, as well as the non-classical DMB and DOB. Marsupial DMB, DAB and DBB have been characterised. Confusion still surrounds the relationship of the marsupial DAB and DBB genes with the classical eutherian class II clusters. Here we present the first Monotreme MHC class II β chain sequences. Four MHC class II β chain sequences were isolated from a spleen cDNA library from the short-beaked echidna , and one from a spleen cDNA library from platypus using a brushtail possum DAB probe. Given the non-orthologous relationship of the Monotreme sequences with marsupial and eutherian β chain clusters, we recommend that the five new Monotreme sequences be assigned the nomenclature 'DZB', signifying the description of a new mammalian β chain cluster. Our analysis suggests that all mammalian β chain sequences (except DMB) evolved from a common ancestor. Maximum likelihood analysis places the Monotreme β chain sequences at the base of the mammalian clade, indicating their ancestral status. However, within the mammalian clade, monophyletic clades are not robust, and elucidation of the order of gene duplication that gave rise to the present-day gene clusters is not yet possible.
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echidna iga supports mammalian unity and traditional therian relationship
Mammalian Genome, 2002Co-Authors: Katherine Belov, Lars Hellman, Kyall R Zenger, Desmond W. CooperAbstract:IgA is found only in birds and mammals where it is the principal immunoglobulin class found in secretions, providing protection at mucosal surfaces. The structure of IgA in birds is different from that of marsupials and eutherians. The avian heavy-chain constant region of IgA (Ca) consists of four domains, while marsupial and eutherian Ca consists of three domains plus a hinge. Here we describe the cloning and characterization of the heavy chain of IgA from the short-beaked echidna, Tachyglossus aculeatus, and report that Monotreme Ca is composed of three domains plus a hinge, making it similar to its therian counterparts. The amino acid sequence identity of echidna Ca is approximately 47% with the therians and 30% with birds. Phylogenetic analysis of the Ca sequences provides strong support for the Theria hypothesis, which proposes that Monotremes diverged prior to the separation of marsupial and eutherians, and directly contradicts the results of the mitochondrial data, which support a "Marsupionta" relationship which has marsupials and Monotremes closer to each other. The characterization of the heavy chain of IgA from Monotremes, in conjunction with the recent description of Monotreme IgG and IgE nucleotide sequence, confirms that the 'second big bang' of immunoglobulin evolution predated the divergence of extant mammals.
Julie A. Sharp - One of the best experts on this subject based on the ideXlab platform.
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structural characterization of a novel Monotreme specific protein with antimicrobial activity from the milk of the platypus
Acta Crystallographica Section F-structural Biology and Crystallization Communications, 2018Co-Authors: Janet Newman, Kevin R. Nicholas, Julie A. Sharp, Ashwantha Kumar Enjapoori, John D Bentley, Timothy E Adams, Thomas S PeatAbstract:Monotreme lactation protein (MLP) is a recently identified protein with antimicrobial activity. It is present in the milk of Monotremes and is unique to this lineage. To characterize MLP and to gain insight into the potential role of this protein in the evolution of lactation, the crystal structure of duck-billed platypus (Ornithorhynchus anatinus) MLP was determined at 1.82 A resolution. This is the first structure to be reported for this novel, mammalian antibacterial protein. MLP was expressed as a FLAG epitope-tagged protein in mammalian cells and crystallized readily, with at least three space groups being observed (P1, C2 and P21). A 1.82 A resolution native data set was collected from a crystal in space group P1, with unit-cell parameters a = 51.2, b = 59.7, c = 63.1 A, α = 80.15, β = 82.98, γ = 89.27°. The structure was solved by SAD phasing using a protein crystal derivatized with mercury in space group C2, with unit-cell parameters a = 92.7, b = 73.2, c = 56.5 A, β = 90.28°. MLP comprises a monomer of 12 helices and two short β-strands, with much of the N-terminus composed of loop regions. The crystal structure of MLP reveals no three-dimensional similarity to any known structures and reveals a heretofore unseen fold, supporting the idea that Monotremes may be a rich source for the identification of novel proteins. It is hypothesized that MLP in Monotreme milk has evolved to specifically support the unusual lactation strategy of this lineage and may have played a central role in the evolution of these mammals.
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Identification and Functional Characterization of a Novel Monotreme- Specific Antibacterial Protein Expressed during
2016Co-Authors: Swathi Bisana, Satish Kumar, Peggy Rismiller, Stewart C. Nicol, Kevin R. Nicholas, Julie A. SharpAbstract:Monotremes are the only oviparous mammals and exhibit a fascinating combination of reptilian and mammalian characters. They represent a component of synapsidal reproduction by laying shelled eggs which are incubated outside the mother’s body. This is accompanied by a prototherian lactation process, marking them as representatives of early mammals. The only extant Monotremes are the platypus, and the short- and long- beaked echidnas, and their distributions are limited to Australia and New Guinea. Apart for a short weaning period, milk is the sole source of nutrition and protection for the hatchlings which are altricial and immunologically naive. The duration of lactation in these mammals is prolonged relative to the gestational length and period of incubation of eggs. Much of the development of Monotreme young occurs in the non-sterile ex-utero environment. Therefore the role of milk in the growth, development and disease protection of the young is of significant interest. By sequencing the cDNA of cells harvested from Monotreme milk, we have identified a novel Monotreme- specific transcript, and the corresponding gene was designated as the EchAMP. The expression profile of this gene in various tissues revealed that it is highly expressed in milk cells. The peptides corresponding to the EchAMP protein have been identified in a sample of echidna milk In silico analysis indicated putative antimicrobial potential for the cognate protein of EchAMP. This was further confirmed by in vitro assays using a host of bacteria. Interestingly, EchAMP did not display any activity against a commensal gut floral species. These results support the hypothesis of enhancement of surviva
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Milk | Milk of Monotremes and Marsupials
Reference Module in Food Science, 2016Co-Authors: Julie A. Sharp, Christophe Lefevre, Ashwantha Kumar Enjapoori, Vengama Modepalli, Helen E. Abud, Kevin R. NicholasAbstract:Lactation is a defining feature of mammals. The production of milk by the mammary gland during lactation is generally regarded as a mechanism required to supply nutrition to the neonate before it is able to digest other types of food. Increasing evidence suggests that components of milk have additional functions in addition to nutrition. Monotremes, marsupials and eutherians are all members of the class mammalia, but Monotremes and marsupials have evolved a lactation pattern that is very different from eutherians. In eutherians, the gestation period is long relative to its lactation period. However, in marsupials and Monotremes the gestation period is relatively short. As a result, the newborn is relatively small and undeveloped and most of the early development occurs postnatally. Eutherians produce milk of a constant composition after the expression of the initial colostrum, whereas marsupials such as the tammar wallaby ( Macropus eugenii ), have a short gestation, and give birth to a highly immature young and then commence a long lactation during which the milk production and composition progressively change in composition to suit the needs of the developing young. The comparative study of Monotreme, marsupial and eutherian milk is of significant interest and may reveal bioactives required for developmental processes. These factors may have been either lost, down-regulated or altered/modified in eutherians since most development of eutherian young occurs in utero with nutrition and developmental signaling provided by the amniotic fluid and supplemented from the mother via the placenta.
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Hormonal regulation of platypus Beta-lactoglobulin and Monotreme lactation protein genes.
General and comparative endocrinology, 2015Co-Authors: Ashwantha Kumar Enjapoori, Kevin R. Nicholas, Christophe Lefevre, Julie A. SharpAbstract:Endocrine regulation of milk protein gene expression in marsupials and eutherians is well studied. However, the evolution of this complex regulation that began with Monotremes is unknown. Monotremes represent the oldest lineage of extant mammals and the endocrine regulation of lactation in these mammals has not been investigated. Here we characterised the proximal promoter and hormonal regulation of two platypus milk protein genes, Beta-lactoglobulin (BLG), a whey protein and Monotreme lactation protein (MLP), a Monotreme specific milk protein, using in vitro reporter assays and a bovine mammary epithelial cell line (BME-UV1). Insulin and dexamethasone alone provided partial induction of MLP, while the combination of insulin, dexamethasone and prolactin was required for maximal induction. Partial induction of BLG was achieved by insulin, dexamethasone and prolactin alone, with maximal induction using all three hormones. Platypus MLP and BLG core promoter regions comprised transcription factor binding sites (e.g. STAT5, NF-1 and C/EBPα) that were conserved in marsupial and eutherian lineages that regulate caseins and whey protein gene expression. Our analysis suggests that insulin, dexamethasone and/or prolactin alone can regulate the platypus MLP and BLG gene expression, unlike those of therian lineage. The induction of platypus milk protein genes by lactogenic hormones suggests they originated before the divergence of marsupial and eutherians.
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Monotreme Lactation Protein Is Highly Expressed in Monotreme Milk and Provides Antimicrobial Protection
Genome biology and evolution, 2014Co-Authors: Ashwantha Kumar Enjapoori, Stewart C. Nicol, Kevin R. Nicholas, Christophe Lefevre, T. R. Grant, Julie A. SharpAbstract:Monotremes (platypus and echidna) are the descendants of the oldest ancestor of all extant mammals distinguished from other mammals by mode of reproduction. Monotremes lay eggs following a short gestation period and after an even briefer incubation period, altricial hatchlings are nourished over a long lactation period with milk secreted by nipple-less mammary patches located on the female’s abdomen. Milk is the sole source of nutrition and immune protection for the developing young until weaning. Using transcriptome and mass spectrometry analysis of milk cells and milk proteins, respectively, a novel Monotreme Lactation Protein (MLP) was identified as a major secreted protein in milk. We show that platypus and short-beaked echidna MLP genes show significant homology and are unique to Monotremes. The MLP transcript was shown to be expressed in a variety of tissues; however, highest expression was observed in milk cells and was expressed constitutively from early to late lactation. Analysis of recombinant MLP showed that it is an N-linked glycosylated protein and biophysical studies predicted that MLP is an amphipathic, α-helical protein, a typical feature of antimicrobial proteins. Functional analysis revealed MLP antibacterial activity against both opportunistic pathogenic Staphylococcus aureus and commensal Enterococcus faecalis bacteria but showed no effect on Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Salmonella enterica. Our data suggest that MLP is an evolutionarily ancient component of milk-mediated innate immunity absent in other mammals. We propose that MLP evolved specifically in the Monotreme lineage supporting the evolution of lactation in these species to provide bacterial protection, at a time when mammals lacked nipples.
