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      • Susceptibility of amphibians to chytridiomycosis is associated with MHC class II conformation

        Bataille, Arnaud,Cashins, Scott D.,Grogan, Laura,Skerratt, Lee F.,Hunter, David,McFadden, Michael,Scheele, Benjamin,Brannelly, Laura A.,Macris, Amy,Harlow, Peter S.,Bell, Sara,Berger, Lee,Waldman, Bru The Royal Society 2015 Proceedings, Biological sciences Vol.282 No.1805

        <P>The pathogenic chytrid fungus <I>Batrachochytrium dendrobatidis</I> (Bd) can cause precipitous population declines in its amphibian hosts. Responses of individuals to infection vary greatly with the capacity of their immune system to respond to the pathogen. We used a combination of comparative and experimental approaches to identify major histocompatibility complex class II (MHC-II) alleles encoding molecules that foster the survival of Bd-infected amphibians. We found that Bd-resistant amphibians across four continents share common amino acids in three binding pockets of the MHC-II antigen-binding groove. Moreover, strong signals of selection acting on these specific sites were evident among all species co-existing with the pathogen. In the laboratory, we experimentally inoculated Australian tree frogs with Bd to test how each binding pocket conformation influences disease resistance. Only the conformation of MHC-II pocket 9 of surviving subjects matched those of Bd-resistant species. This MHC-II conformation thus may determine amphibian resistance to Bd, although other MHC-II binding pockets also may contribute to resistance. Rescuing amphibian biodiversity will depend on our understanding of amphibian immune defence mechanisms against Bd. The identification of adaptive genetic markers for Bd resistance represents an important step forward towards that goal.</P>

      • Characterization of MHC class IA in the endangered southern corroboree frog

        Kosch, Tiffany A.,Eimes, John A.,Didinger, Chelsea,Brannelly, Laura A.,Waldman, Bruce,Berger, Lee,Skerratt, Lee F. Springer-Verlag 2017 Immunogenetics Vol.69 No.3

        <P>Southern corroboree frogs (Pseudophryne corroboree) have declined to near extinction in the wild after the emergence of the amphibian chytrid fungus Batrachochytrium dendrobatidis in southeastern Australia in the 1980s. A major captive breeding and reintroduction program is underway to preserve this iconic species, but improving resistance to B. dendrobatidis would help the wild population to be self-sustaining. Using 3' and 5' rapid amplification of complementary DNA ends (RACE), we characterized the major histocompatibility complex (MHC) class IA locus in this species. We then used sequences generated from RACE to design primers to amplify the peptide-binding region (PBR) of this functional genetic marker. Finally, we analysed the diversity, phylogeny, and selection patterns of PBR sequences from four P. corroboree populations and compared this with other amphibian species. We found moderately high MHC class IA genetic diversity in this species and evidence of strong positive and purifying selection at sites that are associated with putative PBR pockets in other species, indicating that this gene region may be under selection for resistance to Bd. Future studies should focus on identifying alleles associated with Bd resistance in P. corroboree by performing a Bd laboratory challenge study to confirm the functional importance of our genetic findings and explore their use in artificial selection or genetic engineering to increase resistance to chytridiomycosis.</P>

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