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Woolly Mammoth Genome Rife With Interspersed Repeats

NEW YORK (GenomeWeb News) – The woolly mammoth genome contains more interspersed repeats than any other mammal genome so far — a finding that may offer new hints about the evolutionary history of these transposable elements.

Researchers from Pennsylvania State University used both homology-based strategies and other methods to identify interspersed repeats in the woolly mammoth genome. Their results suggest the mammoth genome contains more interspersed repeats than any mammalian genome tested so far — including a type of long interspersed element found in cattle, snakes, and early diverging mammals.

Those involved say the work, which appeared online today in Genome Research, not only provides insights into mammalian history but may also lead to a better understanding of genetic features related to extinction.

In general, researchers classify interspersed repeats or transposable elements into two different groups: retrotransposons, which are transcribed into RNA and reverse transcribed back to DNA before inserting into other parts of the genome, and DNA transposons, which hop directly from one place in the genome to the next.

Retrotransposons may or may not include long terminal repeats, which are used to further distinguish between them. For instance, long and short interspersed repeats make up the non-LTR retrotransposon group.

Although most mammoths became extinct roughly 10,000 years ago, researchers have been able to isolate DNA from mammoth hair and begin gaining insights into the animal's genome. Penn State researcher Stephan Schuster and his colleagues published a paper on the 1X woolly mammoth draft nuclear genome — sequenced using Roche 454 sequencing — last November.

For the most recent paper, the team started looking at the transposable element repertoire in the genome. First, they sifted through mammoth genomic DNA reads to find interspersed repeats using the latest version of the Genetic Information Research Institute's database Repbase and BLASTN comparisons.

They found that long interspersed elements (LINEs) made up just over 30 percent of the mammoth genome sequence, while short interspersed elements (SINEs) represented nearly seven percent. Another seven percent of the sequence was LTR retroposons and about 0.7 percent represented DNA transposons.

The researchers also compared the woolly mammoth genome with a draft version of the elephant genome, the human genome, and also the short-tailed opossum genome, lead author Fangqing Zhao, a post-doctoral researcher in Schuster's lab at Penn State, told GenomeWeb Daily News.

Because some of the mammoth genomic DNA reads they were looking at were unassembled, the team decided to compare the sequences with both assembled and simulated human and opossum genomes.

Their comparisons suggest the woolly mammoth genome contained more transposable elements than any mammalian genomes characterized so far. The total interspersed repeat content was about 45 percent, compared with about 36 percent in the simulated human sequence data and 40 percent in the simulated opossum data.

The mammoth genome was particularly LINE repeat rich. These elements made up more than 30 percent of the mammoth genome sequence. And while the mammoth, human, and opossum genomes all contained mainly L1 type LINE repeats, the interspersed repeats in the mammoth genome appeared to be less divergent than those in humans and opossums.

Along with L1 LINE repeats, the researchers discovered that about 12 percent of the mammoth genome was composed of a type of LINE repeats called RTEs. In contrast, the short-tailed opossum — previously thought to have the most RTE elements — has just two percent or so of its genome composed of RTE elements. Primate genomes, on the other hand, don't seem to contain RTEs at all.

Another surprise: among the RTE repeats was a group of repetitive elements in the BovB/RTE family. Those repeats were previously found in widely divergent groups such as cattle, snakes, and marsupials, Zhao said. Finding these repeats in mammoths supports the notion that BovB/RTE may have been acquired through horizontal gene transfer, he added, spreading from multiple vertebrate donors in different directions.

Although the mammoth genome contained a higher than normal proportion of LINE repeats, SINE repeats were present at a lower frequency than in other animals. DNA transposons also seem to have been rare in the mammoth, making up less than one percent of its genome. In contrast, the human genome contains about 2.5 percent DNA transposons and the opossum genome contains about 1.7 percent transposons.

As they continue unraveling the patterns in the mammoth genome, Zhao explained, researchers may also get new clues about why mammoths became extinct. Although environmental factors likely played a role, Zhao said genetics may also have contributed to the animal's demise. And comparing the mammoth genome with that of creatures living today may provide clues about such genetic factors.

For instance, the extinct woolly mammoth and extant African elephant diverged roughly 7.6 million years ago, Zhao said. Although the genetic difference between them is less than a quarter of a percent at the amino-acid level, he added, repetitive elements tend to evolve much faster than coding regions and can significantly impact genome evolution.

Zhao predicts that once the elephant and mammoth genome are both sequenced more completely, it will be easier to detect structural variations and other differences between them. He and his colleagues are currently using Illumina sequencing to get more complete coverage of the woolly mammoth genome.

Information on the mammoth genome is also available online at Penn State's Mammoth Genome Project.

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