Harmit Malik: Molecular arms races between primate and viral genomes

I. Host evolution
II. Viral evolution

Part I: Host evolution

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Lecture Overview

Malik explains that viruses and their human hosts are constantly undergoing an evolutionary arms race. In this high stakes battle, one party is always losing and thus there is always pressure on the “loser” to innovate. Through cycles of adaptation, the “winner” and “loser” are continually switched. A comparison of human, rhesus macaque and chimpanzee genomes shows that most primate genes have undergone very few changes over time. However, there are a few genes that have undergone many more changes indicating that mutation in these genes may be advantageous. Interestingly, many of these genes are involved in immunity.

In Part 1 of his talk, Malik discusses how primate proteins have evolved to combat viral proteins and specifically viral proteins that mimic host proteins. Malik focuses on the strategy used by the human PKR gene to battle the pox viral protein K3L, a protein that effectively mimics the human protein eIF2a.

In Part 2, Malik switches his focus to adaptation in the virus. K3L is the viral protein targeted by the primate PKR. Just as PKR has rapidly changed in primate genomes, K3L has rapidly changed in the viral genome. Malik and colleagues designed an assay that allowed them to follow the rapid evolution of K3L. They found that the virus adapted by both mutating a single amino acid and by undergoing a series of duplications of the K3L gene. This rapid genomic amplification may be another way by which viruses adapt to a changing host immune system.

Speaker Bio

Harmit Malik received his undergraduate degree in chemical engineering from the Indian Institute of Technology, Bombay and his PhD from the University of Rochester. He moved to the Fred Hutchinson Cancer Research Center in Seattle for post-doctoral work and decided to stay, starting his own lab in the Division of Basic Sciences in 2003. Malik is interested in the evolution of genetic conflict. To this end, his lab studies transposable elements and viruses, as both of these genomic elements are interested only in their own evolutionary success. He also studies the strategies used by primates to defend themselves against attack by viruses. Another part of his lab is interested in understanding how these conflicts between and within genomes shape essential cellular processes, with a special focus on chromosome segregation.

Malik has been awarded numerous prizes for his research including the 2010 Vilcek Prize for Creative Promise in Biomedical Science, a Presidential Early Career Award and a HHMI Early Career Scientist award.

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Recommended Reading

“Genes in Conflict” , A. Burt & R. Trivers, (2008) Harvard University Press 

Elde, N. C., Child, S. J., Geballe, A. P. and Malik, H. S. (2009) Protein Kinase R reveals an evolutionary model for defeating viral mimicry. Nature 457: 485-489.

Emerman, M. and Malik, H. S. (2010) Paleovirology: modern consequences of ancient viruses. (Essay) PLoS Biology 8: e1000301.

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