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DNA Jettisoned From Lamprey Genome During Development

NEW YORK (GenomeWeb News) – In a paper that's scheduled to appear online this week in the Proceedings of the National Academy of Sciences, researchers from the University of Washington and Seattle's Benaroya Research Institute at Virginia Mason found evidence of genome reduction and rearrangement during development in the sea lamprey, a jawless vertebrate.

Development-related genomic rearrangements are "peppered throughout the tree of life," senior author Chris Amemiya, a researcher at Seattle's Benaroya Research Institute at Virginia Mason, told GenomeWeb Daily News. For instance, the hagfish undergoes large genomic rearrangements during the transition from germ line cells to adult tissue. Some flies, roundworms, and other organisms undergo their own genomic shuffling and streamlining as they differentiate.

Such phenomena are intriguing, the researchers noted, because understanding how these changes are tolerated and regulated could provide insights into cases in which genome rearrangement is deleterious — for instance in cancer cells.

"[C]hanges that are tightly regulated in these exceptional genomes are reminiscent of the dysregulated structural changes that give rise to cancers or other genomic disorders," the authors wrote. "In this context, developmentally regulated rearrangements hold great potential for studying the factors that promote genome stability and change in normally developing somatic cells and the means by which alterations in genome structure contribute to the differentiation of cell lineages."

Amemiya and his co-workers became suspicious that the lamprey's genome structure and composition was changing during development when they heard rumors lamprey genome sequences efforts were being complicated by genome fragmentation. They speculated that this might be due to genome rearrangements similar to those described for the hagfish, a chordate and superficially similar organism.

To test this, the researchers compared germ line and somatic tissues from sea lamprey caught in Lake Michigan.

Indeed, they found that the genome was larger in sperm (germ line cells) than in adult blood nuclei (somatic cells), even within the same individual. The sperm cells also contained more DNA than kidney and liver cells, which both had similar DNA content to red blood cells. Overall, the researchers noted, sperm genomes contained some 20 percent more DNA than adult cells such as red blood cells.

And Southern hybridization experiments offered the first view of structural differences between the genomes, lead author Jeremiah Smith, a post-doctoral researcher in Amemiya's lab, told GenomeWeb Daily News. Several bits of DNA differed in size, intensity, and location between sperm and blood cells.

In particular, the researchers found that a stretch of sequence dubbed Germ1 was over-represented in the testes and germ cells, showing up on several different chromosomes. In contrast, its levels were dramatically lower in blood, liver, kidney, tail fin, or muscle cells. The team's subsequent fluorescence in situ hybridization experiments also support the notion that Germ1 sequences are rearranged and/or reduced during development.

When the team sequenced the Germ1 region, compared it with sequences in the NCBI database, and found that it was a mishmash of rDNA sub-unit DNA and non-long terminal repeat retrotransposable element sequence found in bony fish.

Despite the similarities to rDNA sequence, the team speculated that the DNA was not contributing to ribosomal function in the germ line cells, since the sperm cells are typically transcriptionally inactive.

In addition, by following Germ1 in developing embryos for the first few days after fertilization, the researchers could pinpoint the window when Germ1 DNA dropped off—usually between two and three days after fertilization.

Nevertheless, the researchers explained, the amount of Germ1 sequence lost during development is not enough to explain the overall difference in genome size between sperm and blood cells, suggesting Germ1 is one of several sequences tossed out during development.

By comparing sperm BAC end sequences with whole genome sequence reads, the team found several other sequences that are present in sperm but seemingly absent or diminished in adult lamprey tissue.

While it's still unclear how sequences are removed from the genome during development, Smith said he suspects they might be lost through recombination. And although the function of the sequences is yet to be determined, the fact that the cell seems to toss out the DNA in a consistent way suggests they are functionally important, the researchers explained.

"Somehow during development, it's jettisoning these genes which — at least in one case — are clearly functional in the germ line," Amemiya said.

The researchers are currently doing follow-up experiments to begin characterizing lost sequences that are not highly repetitive. They are also starting to delve into other species to try to figure out which other organisms, if any, undergo genomic rearrangement during development and how this process tracks with early vertebrate evolution.

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