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Botryllus Schlloseri genome project
Urochordates like B. schlosseri are considered to be the closest living invertebrate relatives of vertebrates. Using a novel method for high-throughput sequencing of eukaryotic genomes, we sequenced and assembled 580 Mbp of the B. schlosseri genome. The genome assembly is comprised of nearly 14,000 intron-containing predicted genes, and 13,500 intron-less predicted genes, 40% of which could be confidently parceled into 13 (of 16 haploid) chromosomes. A comparison of homologous genes between B. schlosseri and other diverse taxonomic groups revealed genomic events underlying the evolution of vertebrates and lymphoid-mediated immunity. The B. schlosseri genome is a community resource for studying alternative modes of reproduction, natural transplantation reactions, and stem cell-mediated regeneration.

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Cellular and Molecular Mechanisms of Aging and Regeneration in Botryllus schlosseri
In colonial organisms, like Botryllus schlosseri, individuals originally derived, like us, by sexual reproduction and chordate development, can metamorphose to clonal founders that undergo weekly formation of new individuals by budding from a small group of stem cells. Individuals are transient structures which die through massive apoptosis and successive buds mature to replicate an entire new body, every week (see Video 1). As a result, their stem cells, which are the only self renewing cells in a tissue, are the only cells which remain through the entire life of the genotype and are the only cells that can retain the effects of time. Therefore, aging of the colony in this organism is, by definition, aging of the stem cells: every other cell is regenerated from them on a cycle basis. In this colonial model organism, we can clearly define that stem cell aging is the root cause of senescence of the entire colony. We use genetic, genomic, and cell biological approaches to investigate the evolutionary molecular mechanisms that regulate blastogenesis, regeneration and the decline of tissue regenerative potential during aging.

Molecular Characterization of Predatory Stem Cells in a Chimeric Protochordate
Botryllus schlosseri is a clonal colonial tunicate that undergoes self/nonself recognition and responses in the wild. The colonies may be a single individual or the asexually reproduced clonal progeny of the founder, all linked by a common extracorporeal vasculature embedded in a gelatinous tunic. When two individuals or colonies contact each other on subtidal surfaces, the blind-ended ampullar vessels between colonies may anastomose, or undergo an inflammatory rejection, with formation of a scar between them. We showed in 1982 that fusion or rejection was determined by a single, very highly polymorphic gene locus [called Fu/HC], where sharing of one or two alleles leads to vascular fusion, and sharing of none leads to rejection. We later cloned a candidate gene family of alleles of this locus, which has the characteristics of a complex allelic polymorphism. Candidate receptors for the gene have also been discovered.

In Botryllus chimeras the adult circulating stem cells of one partner can compete and replace the germ line and/or the soma of the other partner (termed germ line or somatic stem cell parasitism). This ability to replace host tissues follows genetic (heritable) hierarchies of "winner strain" that replace "loser strain" tissues. We have proposed that fusion or rejection regulated by Fu/HC limits fusion and stem cell sharing to kin, especially important in germline stem cell competitions. We use genetic, genomic, and cell biological approaches to investigate: The evolutionary molecular mechanisms that regulate allogeneic stem cell competition in host.