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Lampreys are representatives of an ancient vertebrate lineage that diverged from our own ∼500 million years ago. By virtue of this deeply shared ancestry, the sea lamprey (P. marinus) genome is uniquely poised to provide insight into the ancestry of vertebrate genomes and the underlying principles of vertebrate biology. Here, we present the first lamprey(More)
Jawless vertebrates use variable lymphocyte receptors (VLR) comprised of leucine-rich-repeat (LRR) segments as counterparts of the immunoglobulin-based receptors that jawed vertebrates use for antigen recognition. Highly diverse VLR genes are somatically assembled by the insertion of variable LRR sequences into incomplete germline VLRA and VLRB genes. Here(More)
BAFF (TNF superfamily [TNFSF] 13B/Blys) and APRIL (TNFSF13) are important regulatory factors for lymphocyte activation and survival in mammals. A BAFF/APRIL-like relative called BAFF- and APRIL-like molecule (BALM) has also been identified in cartilaginous and bony fishes, and we report in this study a BAFF-like gene in lampreys. Our phylogenetic analysis(More)
BACKGROUND Cryopyrin-associated periodic syndrome (CAPS) is a group of rare autoinflammatory diseases, and of these, chronic infantile neurologic, cutaneous, and articular/neonatal-onset multisystem inflammatory disease (CINCA/NOMID) syndrome has the most severe phenotype. Canakinumab, a monoclonal antibody that targets interleukin-1β, has been shown to be(More)
BACKGROUND The natural course of submacular hemorrhage resulting from traumatic choroidal rupture generally has a poor outcome unless treated. The intravitreal injection of gas only or gas with recombinant tissue plasminogen activator (rt-PA) has been reported to be effective, but has also been reported to induce severe complications such as retinal(More)
Immunologists and evolutionary biologists have been debating the nature of the immune system of jawless vertebrates--lampreys and hagfish--since the nineteenth century. In the past 50 years, these fish were shown to have antibody-like responses and the capacity to reject allografts but were found to lack the immunoglobulin-based adaptive immune system of(More)
A surprising number of Fc receptor (FcR) relatives have been recognized recently with the potential capacity to modulate innate and adaptive immune responses. The six human FcR homologs (FcRH1-6), which belong to a phylogenetically conserved gene family, have variable numbers of extracellular immunoglobulin domains of five different subtypes. FcRH(More)
Clusters of localized hypermutation in human breast cancer genomes, named “kataegis” (from the Greek for thunderstorm), are hypothesized to result from multiple cytosine deaminations catalyzed by AID/APOBEC proteins. However, a direct link between APOBECs and kataegis is still lacking. We have sequenced the genomes of yeast mutants induced in diploids by(More)
Approximately 500 million years ago, two types of recombinatorial adaptive immune systems (AISs) arose in vertebrates. The jawed vertebrates diversify their repertoire of immunoglobulin domain-based T and B cell antigen receptors mainly through the rearrangement of V(D)J gene segments and somatic hypermutation, but none of the fundamental AIS recognition(More)
Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems. Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily. Cyclostomes, the lampreys and hagfish, instead use leucine-rich repeat proteins to construct variable lymphocyte receptors (VLRs), two types of which,(More)