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Camilla M Whittington - One of the best experts on this subject based on the ideXlab platform.
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proteomics and deep sequencing comparison of seasonally active venom glands in the Platypus reveals novel venom peptides and distinct expression profiles
Molecular & Cellular Proteomics, 2012Co-Authors: Emily S. W. Wong, Marilyn B. Renfree, Camilla M Whittington, David Morgenstern, Ehtesham Mofiz, Sara Gombert, Katrina Morris, Peter Templesmith, Glenn F King, Welsey C WarrenAbstract:The Platypus is a venomous monotreme. Male Platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of Platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in Platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.
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A Limited Role for Gene Duplications in the Evolution of Platypus Venom
Molecular biology and evolution, 2011Co-Authors: Emily S. W. Wong, Wesley C. Warren, Camilla M Whittington, Anthony T Papenfuss, Katherine BelovAbstract:Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic Platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 Platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the “venome” of the Platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.
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novel venom gene discovery in the Platypus
Genome Biology, 2010Co-Authors: Emily S. W. Wong, Richard K. Wilson, Camilla M Whittington, Anthony T Papenfuss, Devin P Locke, Elaine R Mardis, Sahar Abubucker, Makedonka Mitreva, Arthur HsuAbstract:To date, few peptides in the complex mixture of Platypus venom have been identified and sequenced, in part due to the limited amounts of Platypus venom available to study. We have constructed and sequenced a cDNA library from an active Platypus venom gland to identify the remaining components. We identified 83 novel putative Platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of Platypus envenomation. This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative Platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom.
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ornithorhynchus anatinus Platypus links the evolution of immunoglobulin genes in eutherian mammals and nonmammalian tetrapods
Journal of Immunology, 2009Co-Authors: Yaofeng Zhao, Camilla M Whittington, Lars Hellman, Huiting Cui, Zhiguo Wei, Xiaofeng Zhang, Ziding Zhang, Liming Ren, Yaping Zhang, Katherine BelovAbstract:The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the Platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-omicron-gamma2-gamma1-alpha1-epsilon-alpha2 order, spanning a total of approximately 200 kb DNA, encoding six distinct isotypes. The omicron (omicron for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to upsilon (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The Platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The Platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.
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Understanding and utilising mammalian venom via a Platypus venom transcriptome.
Journal of Proteomics, 2009Co-Authors: Camilla M Whittington, Wesley C. Warren, Philip W Kuchel, Anthony T Papenfuss, Allan M Torres, Jennifer M. S. Koh, Katherine BelovAbstract:Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the Platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to Platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of Platypus venom will eventually yield novel drugs and new targets for painkillers.
Katherine Belov - One of the best experts on this subject based on the ideXlab platform.
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Echidna venom gland transcriptome provides insights into the evolution of monotreme venom
PloS one, 2013Co-Authors: Emily S. W. Wong, Stewart C. Nicol, Wesley C. Warren, Katherine BelovAbstract:Monotremes (echidna and Platypus) are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male Platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a Platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the Platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the Platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna “venom” may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.
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A Limited Role for Gene Duplications in the Evolution of Platypus Venom
Molecular biology and evolution, 2011Co-Authors: Emily S. W. Wong, Wesley C. Warren, Camilla M Whittington, Anthony T Papenfuss, Katherine BelovAbstract:Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic Platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 Platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the “venome” of the Platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.
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ornithorhynchus anatinus Platypus links the evolution of immunoglobulin genes in eutherian mammals and nonmammalian tetrapods
Journal of Immunology, 2009Co-Authors: Yaofeng Zhao, Camilla M Whittington, Lars Hellman, Huiting Cui, Zhiguo Wei, Xiaofeng Zhang, Ziding Zhang, Liming Ren, Yaping Zhang, Katherine BelovAbstract:The evolutionary origins of mammalian immunoglobulin H chain isotypes (IgM, IgD, IgG, IgE, and IgA) are still incompletely understood as these isotypes differ considerably in structure and number from their counterparts in nonmammalian tetrapods. We report in this study that the Platypus (Ornithorhynchus anatinus) Ig H chain constant region gene locus contains eight Ig encoding genes, which are arranged in an mu-delta-omicron-gamma2-gamma1-alpha1-epsilon-alpha2 order, spanning a total of approximately 200 kb DNA, encoding six distinct isotypes. The omicron (omicron for Ornithorhynchus) gene encodes a novel Ig H chain isotype that consists of four constant region domains and a hinge, and is structurally different from any of the five known mammalian Ig classes. This gene is phylogenetically related to upsilon (epsilon) and gamma, and thus appears to be a structural intermediate between these two genes. The Platypus delta gene encodes ten heavy chain constant region domains, lacks a hinge region and is similar to IgD in amphibians and fish, but strikingly different from that in eutherian mammals. The Platypus Ig H chain isotype repertoire thus shows a unique combination of genes that share similarity both to those of nonmammalian tetrapods and eutherian animals and demonstrates how phylogenetically informative species can be used to reconstruct the evolutionary history of functionally important genes.
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Understanding and utilising mammalian venom via a Platypus venom transcriptome.
Journal of Proteomics, 2009Co-Authors: Camilla M Whittington, Wesley C. Warren, Philip W Kuchel, Anthony T Papenfuss, Allan M Torres, Jennifer M. S. Koh, Katherine BelovAbstract:Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the Platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to Platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of Platypus venom will eventually yield novel drugs and new targets for painkillers.
Ken W.s. Ashwell - One of the best experts on this subject based on the ideXlab platform.
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Development of the dorsal and ventral thalamus in Platypus (Ornithorhynchus anatinus) and short-beaked echidna (Tachyglossus aculeatus)
Brain Structure and Function, 2012Co-Authors: Ken W.s. AshwellAbstract:The living monotremes (Platypus and echidnas) are distinguished from therians as well as each other in part by the unusual structure of the thalamus in each. In particular, the Platypus has an enlarged ventral posterior (VP) nucleus reflecting the great behavioural importance of trigeminosensation and electroreception. The embryological collections of the Museum für Naturkunde in Berlin were used to analyse the development of the dorsal thalamus and ventral thalamus (prethalamus) in both species. Prosomeric organization of the forebrain emerged at 6 mm crown-rump length (CRL), but thalamic neurogenesis did not commence until about 8–9 mm CRL. Distinctive features of the dorsal thalamus in the two species began to emerge after hatching (about 14–15 mm CRL). During the first post-hatching week, dense clusters of granular cells aggregated to form the VP of the Platypus, whereas the VP complex of the echidna remained smaller and divided into distinct medial and lateral divisions. At the end of the first post-hatching week, the thalamocortical tract was much larger in the Platypus than the echidna. The dorsal thalamus of the Platypus is essentially adult-like by the sixth week of post-hatching life. The similar appearance of the dorsal thalamus in the two species until the time of hatching, followed by the rapid expansion of the VP in the Platypus, is most consistent with ancestral Platypuses having undergone changes in the genetic control of thalamic neurogenesis to produce a large VP for trigeminal electroreception after the divergence of the two lineages of monotreme.
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distinct development of peripheral trigeminal pathways in the Platypus ornithorhynchus anatinus and short beaked echidna tachyglossus aculeatus
Brain Behavior and Evolution, 2012Co-Authors: Ken W.s. Ashwell, Craig D. Hardman, Peter GiereAbstract:The extant monotremes (Platypus and echidnas) are believed to all be capable of electroreception in the trigeminal pathways, although they differ significantly in the number and distribution of electroreceptors. It has been argued by some authors that electroreception was first developed in an aquatic environment and that echidnas are descended from a Platypus-like ancestor that invaded an available terrestrial habitat. If this were the case, one would expect the developmental trajectories of the trigeminal pathways to be similar in the early stages of Platypus and short-beaked echidna development, with structural divergence occurring later. We examined the development of the peripheral trigeminal pathway from snout skin to trigeminal ganglion in sectioned material in the Hill and Hubrecht collections to test for similarities and differences between the two during the development from egg to adulthood. Each monotreme showed a characteristic and different pattern of distribution of developing epidermal sensory gland specializations (electroreceptor primordia) from the time of hatching. The cross-sectional areas of the trigeminal divisions and the volume of the trigeminal ganglion itself were also very different between the two species at embryonic ages, and remained consistently different throughout post-hatching development. Our findings indicate that the trigeminal pathways in the short-beaked echidna and the Platypus follow very different developmental trajectories from the earliest ages. These findings are more consistent with the notion that the Platypus and echidna have both diverged from an ancestor with rudimentary electroreception and/or trigeminal specialization, rather than the contention that the echidna is derived from a Platypus-like ancestor.
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the anterior olfactory nucleus and piriform cortex of the echidna and Platypus
Brain Behavior and Evolution, 2006Co-Authors: Ken W.s. Ashwell, Jennifer M PhillipsAbstract:The cyto- and chemoarchitecture of the anterior olfactory nucleus and piriform cortex of the short-beaked echidna and Platypus were studied to determine: (1) if these areas contain chemically distinct
Philip W Kuchel - One of the best experts on this subject based on the ideXlab platform.
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comparative nmr studies of diffusional water permeability of red blood cells from different species xviii Platypus ornithorhynchus anatinus and saltwater crocodile crocodylus porosus
Cell Biology International, 2010Co-Authors: Gheorghe Benga, Bogdan E Chapman, Guy Cox, Philip W KuchelAbstract:As part of a programme of comparative measurements of Pd (diffusional water permeability) the RBCs (red blood cells) from an aquatic monotreme, Platypus (Ornithorhynchus anatinus), and an aquatic reptile, saltwater crocodile (Crocodylus porosus) were studied. The mean diameter of Platypus RBCs was estimated by light microscopy and found to be approximately 6.3 microm. Pd was measured by using an Mn2+-doping 1H NMR (nuclear magnetic resonance) technique. The Pd (cm/s) values were relatively low: approximately 2.1 x 10(-3) at 25 degrees C, 2.5 x 10(-3) at 30 degrees C, 3.4 x 10(-3) at 37 degrees C and 4.5 at 42 degrees C for the Platypus RBCs and approximately 2.8 x 10(-3) at 25 degrees C, 3.2 x 10(-3) at 30 degrees C, 4.5 x 10(-3) at 37 degrees C and 5.7 x 10(-3) at 42 degrees C for the crocodile RBCs. In parallel with the low water permeability, the Ea,d (activation energy of water diffusion) was relatively high, approximately 35 kJ/mol. These results suggest that "conventional" WCPs (water channel proteins), or AQPs (aquaporins), are probably absent from the plasma membranes of RBCs from both the Platypus and the saltwater crocodile.
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Understanding and utilising mammalian venom via a Platypus venom transcriptome.
Journal of Proteomics, 2009Co-Authors: Camilla M Whittington, Wesley C. Warren, Philip W Kuchel, Anthony T Papenfuss, Allan M Torres, Jennifer M. S. Koh, Katherine BelovAbstract:Only five mammalian species are known to be venomous, and while a large amount of research has been carried out on reptile venom, mammalian venom has been poorly studied to date. Here we describe the status of current research into the venom of the Platypus, a semi-aquatic egg-laying Australian mammal, and discuss our approach to Platypus venom transcriptomics. We propose that such construction and analysis of mammalian venom transcriptomes from small samples of venom gland, in tandem with proteomics studies, will allow the identification of the full range of mammalian venom components. Functional studies and pharmacological evaluation of the identified toxins will then lay the foundations for the future development of novel biomedical substances. A large range of useful molecules have already been identified in snake venom, and many of these are currently in use in human medicine. It is therefore hoped that this basic research to identify the constituents of Platypus venom will eventually yield novel drugs and new targets for painkillers.
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d amino acid residue in a defensin like peptide from Platypus venom effect on structure and chromatographic properties
Biochemical Journal, 2005Co-Authors: Allan M Torres, Paramjit S Bansal, Paul F Alewood, Chryssanthi Tsampazi, D P Geraghty, Philip W KuchelAbstract:The recent discovery that the natriuretic peptide OvCNPb (Ornithorhynchus venom C-type natriuretic peptide B) from Platypus (Ornithorynchus anatinus) venom contains a D-amino acid residue suggested that other D-amino-acid-containing peptides might be present in the venom. In the present study, we show that DLP-2 (defensin-like peptide-2), a 42-amino-acid residue polypeptide in the Platypus venom, also contains a D-amino acid residue, D-methionine, at position 2, while DLP-4, which has an identical amino acid sequence, has all amino acids in the L-form. These findings were supported further by the detection of isomerase activity in the Platypus gland venom extract that converts DLP-4 into DLP-2. In the light of this new information, the tertiary structure of DLP-2 was recalculated using a new structural template with D-Met2. The structure of DLP-4 was also determined in order to evaluate the effect of a D-amino acid at position 2 on the structure and possibly to explain the large retention time difference observed for the two molecules in reverse-phase HPLC. The solution structures of the DLP-2 and DLP-4 are very similar to each other and to the earlier reported structure of DLP-2, which assumed that all amino acids were in the L-form. Our results suggest that the incorporation of the D-amino acid at position 2 has minimal effect on the overall fold in solution.
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d amino acid residue in the c type natriuretic peptide from the venom of the mammal ornithorhynchus anatinus the australian Platypus
FEBS Letters, 2002Co-Authors: Allan M Torres, Paramjit S Bansal, Ian Menz, Paul F Alewood, Jelle Lahnstein, C H Gallagher, Philip W KuchelAbstract:The C-type natriuretic peptide from the Platypus venom (OvCNP) exists in two forms, OvCNPa and OvCNPb, whose amino acid sequences are identical. Through the use of nuclear magnetic resonance, mass spectrometry, and peptidase digestion studies, we discovered that OvCNPb incorporates a D-amino acid at position 2 in the primary structure. Peptides containing a D-amino acid have been found in lower forms of organism, but this report is the first for a D-amino acid in a biologically active peptide from a mammal. The result implies the existence of a specific isomerase in the Platypus that converts an L-amino acid residue in the protein to the D-configuration.
Emily S. W. Wong - One of the best experts on this subject based on the ideXlab platform.
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Echidna venom gland transcriptome provides insights into the evolution of monotreme venom
PloS one, 2013Co-Authors: Emily S. W. Wong, Stewart C. Nicol, Wesley C. Warren, Katherine BelovAbstract:Monotremes (echidna and Platypus) are egg-laying mammals. One of their most unique characteristic is that males have venom/crural glands that are seasonally active. Male Platypuses produce venom during the breeding season, delivered via spurs, to aid in competition against other males. Echidnas are not able to erect their spurs, but a milky secretion is produced by the gland during the breeding season. The function and molecular composition of echidna venom is as yet unknown. Hence, we compared the deeply sequenced transcriptome of an in-season echidna crural gland to that of a Platypus and searched for putative venom genes to provide clues into the function of echidna venom and the evolutionary history of monotreme venom. We found that the echidna venom gland transcriptome was markedly different from the Platypus with no correlation between the top 50 most highly expressed genes. Four peptides found in the venom of the Platypus were detected in the echidna transcriptome. However, these genes were not highly expressed in echidna, suggesting that they are the remnants of the evolutionary history of the ancestral venom gland. Gene ontology terms associated with the top 100 most highly expressed genes in echidna, showed functional terms associated with steroidal and fatty acid production, suggesting that echidna “venom” may play a role in scent communication during the breeding season. The loss of the ability to erect the spur and other unknown evolutionary forces acting in the echidna lineage resulted in the gradual decay of venom components and the evolution of a new role for the crural gland.
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proteomics and deep sequencing comparison of seasonally active venom glands in the Platypus reveals novel venom peptides and distinct expression profiles
Molecular & Cellular Proteomics, 2012Co-Authors: Emily S. W. Wong, Marilyn B. Renfree, Camilla M Whittington, David Morgenstern, Ehtesham Mofiz, Sara Gombert, Katrina Morris, Peter Templesmith, Glenn F King, Welsey C WarrenAbstract:The Platypus is a venomous monotreme. Male Platypuses possess a spur on their hind legs that is connected to glands in the pelvic region. They produce venom only during the breeding season, presumably to fight off conspecifics. We have taken advantage of this unique seasonal production of venom to compare the transcriptomes of in- and out-of-season venom glands, in conjunction with proteomic analysis, to identify previously undiscovered venom genes. Comparison of the venom glands revealed distinct gene expression profiles that are consistent with changes in venom gland morphology and venom volumes in and out of the breeding season. Venom proteins were identified through shot-gun sequenced venom proteomes of three animals using RNA-seq-derived transcripts for peptide-spectral matching. 5,157 genes were expressed in the venom glands, 1,821 genes were up-regulated in the in-season gland, and 10 proteins were identified in the venom. New classes of Platypus-venom proteins identified included antimicrobials, amide oxidase, serpin protease inhibitor, proteins associated with the mammalian stress response pathway, cytokines, and other immune molecules. Five putative toxins have only been identified in Platypus venom: growth differentiation factor 15, nucleobindin-2, CD55, a CXC-chemokine, and corticotropin-releasing factor-binding protein. These novel venom proteins have potential biomedical and therapeutic applications and provide insights into venom evolution.
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A Limited Role for Gene Duplications in the Evolution of Platypus Venom
Molecular biology and evolution, 2011Co-Authors: Emily S. W. Wong, Wesley C. Warren, Camilla M Whittington, Anthony T Papenfuss, Katherine BelovAbstract:Gene duplication followed by adaptive selection is believed to be the primary driver of venom evolution. However, to date, no studies have evaluated the importance of gene duplications for venom evolution using a genomic approach. The availability of a sequenced genome and a venom gland transcriptome for the enigmatic Platypus provides a unique opportunity to explore the role that gene duplication plays in venom evolution. Here, we identify gene duplication events and correlate them with expressed transcripts in an in-season venom gland. Gene duplicates (1,508) were identified. These duplicated pairs (421), including genes that have undergone multiple rounds of gene duplications, were expressed in the venom gland. The majority of these genes are involved in metabolism and protein synthesis not toxin functions. Twelve secretory genes including serine proteases, metalloproteinases, and protease inhibitors likely to produce symptoms of envenomation such as vasodilation and pain were detected. Only 16 of 107 Platypus genes with high similarity to known toxins evolved through gene duplication. Platypus venom C-type natriuretic peptides and nerve growth factor do not possess lineage-specific gene duplicates. Extensive duplications, believed to increase the potency of toxic content and promote toxin diversification, were not found. This is the first study to take a genome-wide approach in order to examine the impact of gene duplication on venom evolution. Our findings support the idea that adaptive selection acts on gene duplicates to drive the independent evolution and functional diversification of similar venom genes in venomous species. However, gene duplications alone do not explain the “venome” of the Platypus. Other mechanisms, such as alternative splicing and mutation, may be important in venom innovation.
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novel venom gene discovery in the Platypus
Genome Biology, 2010Co-Authors: Emily S. W. Wong, Richard K. Wilson, Camilla M Whittington, Anthony T Papenfuss, Devin P Locke, Elaine R Mardis, Sahar Abubucker, Makedonka Mitreva, Arthur HsuAbstract:To date, few peptides in the complex mixture of Platypus venom have been identified and sequenced, in part due to the limited amounts of Platypus venom available to study. We have constructed and sequenced a cDNA library from an active Platypus venom gland to identify the remaining components. We identified 83 novel putative Platypus venom genes from 13 toxin families, which are homologous to known toxins from a wide range of vertebrates (fish, reptiles, insectivores) and invertebrates (spiders, sea anemones, starfish). A number of these are expressed in tissues other than the venom gland, and at least three of these families (those with homology to toxins from distant invertebrates) may play non-toxin roles. Thus, further functional testing is required to confirm venom activity. However, the presence of similar putative toxins in such widely divergent species provides further evidence for the hypothesis that there are certain protein families that are selected preferentially during evolution to become venom peptides. We have also used homology with known proteins to speculate on the contributions of each venom component to the symptoms of Platypus envenomation. This study represents a step towards fully characterizing the first mammal venom transcriptome. We have found similarities between putative Platypus toxins and those of a number of unrelated species, providing insight into the evolution of mammalian venom.
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defensins and the convergent evolution of Platypus and reptile venom genes
Genome Research, 2008Co-Authors: Camilla M Whittington, Emily S. W. Wong, Anthony T Papenfuss, Paramjit S Bansal, Allan M Torres, Janine E Deakin, Tina Graves, Amber E Alsop, Kyriena Schatzkamer, Colin KremitzkiAbstract:When the Platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist’s hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male Platypuses have venomous spurs on each hind leg. The Platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the Platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of Platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these Platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of Platypus and reptile venom. Here we show that several venom components have evolved separately in the Platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.
