Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.

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Population declines and extinctions of amphibians have been attributed to the chytrid fungus Batrachochytrium dendrobatidis (Bd), especially one globally emerging recombinant lineage ('Bd-GPL'). We used PCR assays that target the ribosomal internal transcribed spacer region (ITS) of Bd to determine the prevalence and genetic diversity of Bd in South Korea, where Bd is widely distributed but is not known to cause morbidity or mortality in wild populations. We isolated Korean Bd strains from native amphibians with low infection loads and compared them to known worldwide Bd strains using 19 polymorphic SNP and microsatellite loci. Bd prevalence ranged between 12.5 and 48.0%, in 11 of 17 native Korean species, and 24.7% in the introduced bullfrog Lithobates catesbeianus. Based on ITS sequence variation, 47 of the 50 identified Korean haplotypes formed a group closely associated with a native Brazilian Bd lineage, separated from the Bd-GPL lineage. However, multilocus genotyping of three Korean Bd isolates revealed strong divergence from both Bd-GPL and the native Brazilian Bd lineages. Thus, the ITS region resolves genotypes that diverge from Bd-GPL but otherwise generates ambiguous phylogenies. Our results point to the presence of highly diversified endemic strains of Bd across Asian amphibian species. The rarity of Bd-GPL-associated haplotypes suggests that either this lineage was introduced into Korea only recently or Bd-GPL has been outcompeted by native Bd strains. Our results highlight the need to consider possible complex interactions among native Bd lineages, Bd-GPL and their associated amphibian hosts when assessing the spread and impact of Bd-GPL on worldwide amphibian populations.

The pathogenic chytrid fungus Batrachochytrium dendrobatidis (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.

Objective. To investigate whether heterozygosity for a loss-of-function mutation in the gene encoding the ␣1 chain of type XI collagen (Col11a1) in mice (chondrodysplasia, cho) causes osteoarthritis (OA), and to understand the biochemical and biomechanical effects of this mutation on articular cartilage in knee and temporomandibular (TM) joints.Methods. Articular cartilage from the knee and TM joints of mice heterozygous for cho (cho/؉) and their wild-type littermates (؉/؉) was examined. The morphologic properties of cartilage were evaluated, and collagen fibrils were examined by transmission electron microscopy. Immunohistochemical staining was performed to examine the protein expression levels of matrix metalloproteinase 3 (MMP-3) and MMP-13 in knee joints. In 6-month-old animals, fixed-charge density was determined using a semiquantitative histochemical method, and tensile stiffness was determined using an osmotic loading technique.Results. The diameter of collagen fibrils in articular cartilage of knee joints from heterozygous cho/؉ mice was increased relative to that in control cartilage, and histologic analysis showed OA-like degenerative changes in knee and TM joints, starting at age 3 months. The changes became more severe with aging. At 3 months, protein expression for MMP-3 was increased in knee joints from cho/؉ mice. At 6 months, protein expression for MMP-13 was higher in knee joints from cho/؉ mice than in joints from their wild-type littermates, and negative fixed-charge density was significantly decreased. Moreover, tensile stiffness in articular cartilage of knee joints from cho/؉ mice was moderately reduced and was inversely correlated with the increase in articular cartilage degeneration. Conclusion. Heterozygosity for a loss-of-function mutation inCol11a1 results in the development of OA in the knee and TM joints of cho/؉ mice. Morphologic and biochemical evidence of OA appears to precede significant mechanical changes, suggesting that the cho mutation leads to OA through a mechanism that does not initially involve mechanical factors.Osteoarthritis (OA) is the most frequently occurring degenerative joint disease in the US (1). Although the precise mechanisms by which OA is initiated and progresses are largely unknown, there is growing evidence suggesting that single-gene mutations can, in some cases, be predisposing factors for the disease. For instance, mutations in the genes coding for type II collagen (COL2A1), type IX collagen (COL9A1, COL9A2, and COL9A3), and type XI collagen (COL11A1 and COL11A2) are responsible for earlyonset OA associated with variable degrees of chondrodysplasia in humans (2-6). Understanding the mechanisms underlying the OA caused by collagen mutations will not only broaden our knowledge of OA pathogenesis but may also provide valuable information for the identification of novel therapeutic targets for the treatment of OA.We have previously identified a mutation in Col11a1 as the genetic cause of chondrodysplasia (cho) in mice. The mutation, a single-nucleotide dele...