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International Team Sequences and Assembles Sea Lamprey Genome

NEW YORK (GenomeWeb News) – An international team led by investigators at the Michigan State University and the University of Kentucky have sequenced and assembled the genome of sea lamprey, Petromyzon marinus, using the sequence to begin refining their understanding of vertebrate evolution. Their work was published online yesterday in Nature Genetics.

"The lamprey genome provides an important resource for reconstructing vertebrate origins and the evolutionary events that have shaped the genomes of extant organisms," senior author Weiming Li, with MSU's Department of Fisheries and Wildlife, and colleagues explained.

Lampreys have long-fascinated biologists due to their proposed position in the vertebrate family tree: the lamprey lineage branched off from a shared ancestor that also spawned the hagfish lineage, ancestors of jawed vertebrates — known as gnathostomes — and other, now extinct, lineages.

"Given the critical phylogenetic position of the lamprey as an outgroup to the gnathostomes," Li and colleagues explained, "comparing the lamprey genome to gnathostome genomes holds the promise of providing insights into the structure and gene content of the ancestral vertebrate genome."

Despite its potential for providing insights into vertebrate evolution, though, the lamprey genome had previously proven tough to sequence, authors of the current study explained, owing to the its extensive repetitive element content and the lack of a related reference sequence.

Further complicating the sequencing process is the genome's preponderance of guanine and cytosine bases, which can befuddle some high-throughput sequencing instruments, leading to an over- or under-representation of these GC reads.

For the new study, members of the team from Washington University's Genome Institute tackled the lamprey genome with whole-genome shotgun sequencing, fosmid sequencing, and BAC library sequencing, using genomic DNA from a female sea lamprey caught wild in the Great Lakes. Collaborators at the MSU Genomic Core sequenced lamprey RNA, meanwhile, generated transcriptome data that helped in annotating the newly sequenced genome.

The team's analyses of the 816 million base genome assembly uncovered 26,046 predicted protein-coding genes. Among them were members of 224 gene families that appear to be shared between the lamprey and at least one jawed vertebrate but missing from invertebrate animals.

Almost 35 percent of the existing genome assembly is made up of sequences representing repetitive elements from thousands of families, researchers reported.

Even so, they explained that repeats may actually make up a somewhat larger proportion of the overall lamprey genome, since some repetitive element sequences are unwittingly collapsed by genome assembly software.

Through comparisons with sequences from jawed animals, researchers saw shared chromosomal organization between the lamprey and these gnathostomes. The two lineages also shared sequences from hundreds of conserved non-coding elements.

While homologous to conserved non-coding sequences in the jawed vertebrate genomes, though, the lamprey versions of these elements shared sequence identity over around half of each element, on average.

More research is needed to know just why that is, the group explained, though it may reflect either rapid sequence change in the lamprey lineage or else a splitting off by the lamprey ancestor prior to complete sequence conservation in the jawed vertebrates.

Together with data from existing genomes, patterns in the lamprey genome point to at least two whole-genome duplication events prior to the split between the lamprey lineage and the lineage leading to the jawed vertebrates, researchers noted.

And their additional analyses provided new clues to vertebrate immunity, nervous system function, and development.

For instance, the team saw signs suggesting that the so-called Shh appendage-specific regulatory element, or ShARE, — crucial for limb development in jawed vertebrates — likely appeared within that lineage after the split with the lamprey lineage.

And going forward, the study's authors said, the lamprey genome offers opportunities to explore evolutionary questions, both within the lamprey lineage and across vertebrates as a whole, while at once uncovering new features of lamprey biology.

"This genomic resource holds the promise of providing insights into many other aspects of vertebrate biology, especially with continued refinements in the assembly and the capacity for direct functional analysis in lamprey," they wrote.

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