Genome Project

Botryllus schlloseri genome project

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The Botryllus genome, and the development of the novel method that produced “Synthetic Long Reads” revolutionized the field of next generation sequencing
Voskoboynik et al., eLife

Tunicates are the closest extant relatives of vertebrates and represent an investigative model for evolutionary events leading to adaptive immunity and vertebrate-specific organ/tissue complexity. In 2009, we initiated the Botryllus schlosseri genome project establishing a collaborative group of 19 bioinformatics and molecular and cell biologists from Irv Weissman’s lab, Stephen Quake’s lab, and several international laboratories to gain insight into the evolution and molecular characteristic of stem cell-mediated regeneration, alternative modes of reproduction (sexual vs. a-sexual), and mechanisms of natural transplantation reaction and aging. During this project we developed a novel DNA library prep method for next generation sequencing called synthetic LRseq (Long Read Sequencing) which enables an accurate assembly of the relatively large genome of the Botryllus schlosseri.

Synthetic LRseq, which was later acquired by Illumina, significantly increased the length of a DNA molecule that can be determined by next-generation sequencing (from 100bp to 10,000bp) and allowed the assembling methods to resolve large DNA repeats. The technology we developed and patented is considered more effective than other methods in resolving chromosomal haplotypes. While earlier methods produced an average of the genetic information encoded on each paired chromosome, our method yielded individual results from each chromosome to account for the chromosomal haplotypes with the two different alleles of every polymorphic gene in the B. schlosseri genome. This method is widely used by Illumina, GBI, and other companies for next generation sequencing and has reduced the cost of whole human gDNA sequencing to <$500.

The B. schlosseri genome revealed critical events underlying the early evolution of vertebrates, including the first known appearance of genes related to hematopoiesis, cardiac, optic and auditory development. With over 75% of human genes tracing back to B. schlosseri with at least some sequence homology (e-value ≤e⁻¹⁰), the Botryllus genome, is an important tool for studying stem cells and evolutionary conserved mechanisms of development, regeneration, stem cell competition and aging.