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Harmit Malik: Viral Historian

Member, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington. Age: 38

By | July 1, 2011

KEVIN P. CASEY

When Harmit Malik couldn’t attend a molecular biology seminar at the Indian Institute of Technology due to a class scheduling conflict, the kindly professor invited the young chemical engineering undergraduate to his office to chat about biology one-on-one. Malik sat on a stool across from the professor and listened, transfixed, for two hours. He would visit the professor three times a week for the rest of the semester. “I never missed that appointment,” says Malik.

Soon after receiving his degree in 1993, Malik traveled to New York to attend graduate school at the University of Rochester, one of a few institutions willing to admit a biology PhD student with no background in the life sciences. There, he studied the evolutionary relationships of retrotransposable elements, mobile genetic sequences that amplify themselves in eukaryotic genomes and induce mutations when they insert near or within genes. In 1998, he demonstrated that sequences closely resembling a retrotransposable element found in C. elegans, called RTE-1, are present in the genomes of bovine mammals, rodents, insects, vipers, mollusks, and other species. With his advisor Tom Eickbush, Malik traced the evolution of such elements back to an early eukaryotic ancestor, demonstrating their ability to hitchhike in genomes across millennia.1

METHODS: In early 1999, Malik visited the home of Steve Henikoff of the Fred Hutchinson Cancer Research Center in Seattle to interview for a postdoc position. Henikoff described a recent paper he’d read on an unusually complex protein in the centromere, a specialized chromosomal region that orchestrates sister chromatid separation during cell division. Malik had actually browsed the same paper on the long flight to Seattle, and suggested that the complexity might be due to an evolutionary arms race between chromosomes. “Within 20 minutes of meeting him, he explained to me what we should be doing, and he was absolutely right,” says Henikoff. “He can quickly grasp a problem, even outside his area of expertise, and work out the issues better than anyone I know.”

Two years later, the duo published their theory that centromere complexity is the result of rapid evolution driven by selection pressure for mutations that increase a chromosome’s chance of making it into the egg during meiosis, as only one of the four haploid cells produced by meiosis becomes the oocyte nucleus.2

RESULTS: In 2003, Malik started his own lab at the Hutchinson Center. “I wanted to be in a place that wasn’t all evolutionary biology, but where people study all manners of science,” he says. He took advantage of the center’s collaborative atmosphere, and in 2005, with virologist Michael Emerman, predicted and demonstrated the evolution of a gene, TRIM5a, coding for an innate immune protein that protects against HIV in primates.3 “He’s incredibly creative,” says Emerman. “He doesn’t follow; he’s a leader.”

DISCUSSION: Malik has now turned his attention to ancient viruses, which he studies to understand the evolutionary struggle between viruses and humans. In 2007, he and Emerman re-created a chimeric version of an extinct retrovirus called PtERV1—which infected chimps and gorillas, but not hominids, 4 million years ago—and found that human TRIM5a, which does not defend against HIV, does protect against PtERV1.4 Because human TRIM5a likely evolved to fight PtERV1, it has seemingly left us vulnerable to HIV, says Malik.

Literature Cited

  1. H.S. Malik et al., "The age and evolution of non-LTR retrotransposable elements," Mol Biol Evol, 16:793-805, 1999. (Cited 315 times)
  2. S. Henikoff et al., "The centromere paradox: stable inheritance with rapidly evolving DNA," Science, 293:1098-102, 2001. (Cited 407 times)
  3. S.L. Sawyer et al., "Positive selection of primate TRIM5a identifies a critical species-specific retroviral restriction domain," PNAS, 102:2832-37, 2005. (Cited 274 times)
  4. S.M. Kaiser et al., "Restriction of an extinct retrovirus by the human TRIM5a antiviral protein," Science, 316:1756-58, 2007. (Cited 55 times)

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Comments

Avatar of: edrybicki

edrybicki

Posts: 1457

July 19, 2011

"Methods, Results, Discussion"? Not really very relevant, was it?  Nice article, though!  I'm a sucker for ancient viruses, and especially those trapped in other genomes.

Avatar of:

Posts: 0

July 19, 2011

"Methods, Results, Discussion"? Not really very relevant, was it?  Nice article, though!  I'm a sucker for ancient viruses, and especially those trapped in other genomes.

Avatar of:

Posts: 0

July 19, 2011

"Methods, Results, Discussion"? Not really very relevant, was it?  Nice article, though!  I'm a sucker for ancient viruses, and especially those trapped in other genomes.

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