Ssm Winter 2007 Biomed Pitx1

biology + medicine

Pitx1: How Manatees, Fish, and Mice Lose Their Legs

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anatees gently paddling on the surface of warm waters have revealed a startling connection with fish and mice. These aquatic herbivores are mammals that evolved

from four-legged ancestors into legless swimmers. Stanford Professor David Kingsley of the Developmental Biology Department has recently unraveled one of the secrets behind their evolutionary development, demonstrating that a single gene known as Pitx1 can affect highly divergent species. Discovery of the Pitx1 Gene Through research at the Stanford School of Medicine,

by Erika Williams Kingsley determined that manatees had asymmetrical pelvic bones - the left pelvic bones are larger than their right pelvic bones. Though initially this trait may not appear important, Kingsley had found a similar trend in distinct populations of threespine stickleback, a species of fish that once had pelvic fins. Larger left pelvic bones also pervade in these populations of fish now lacking pelvic fins. What do these legless, asymmetrical animals teach us about evolution? Kingsley discovered that the single gene Pitx1 is present and mutated in both legless manatees and in the populations of stickleback fish lacking pelvic fins. Kingsley’s research in 2004 on stickleback fish showed that different populations had evolved using this Pitx1 mutation in such far-flung regions as Iceland and Vancouver. He proved the gene was single and identical by cross-breeding

Photo Credit: Lynne Lancaster

The same mutations have been used for the same purposes in species that parted ways tens of millions of years ago.

Mice share a commonality with fish and manatees

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the different populations of sticklebacks through in vitro fertilization. Along with Bjarni Jonsson of the Institute of Freshwater Fisheries in Iceland, Kingsley found that all progeny of the fish lacking hind fins retained that characteristic, but when either population was cross-bred with seafaring fish with pelvic fins, all of the next generation had intact pelvic fins. When Pitx1 is mutated in mice, the same effect present in stickleback fish lacking pelvic fins occurs, but with fatal consequences. Not only are the mice born legless and with asymmetrical pelvic bones, but the mutation also affects other characteristics necessary for life. Finding Pitx1 gene expression in different species Inspired by these new findings about sticklebacks and mice, Kingsley decided

Research on mechanisms of evolution in one species can teach about more general evolutionary strategies.

Photo Credit: Troutnut.com

Photo Credit: Bruin Ramsdell

biology + medicine

Above: A Florida manatee swims about legless because of one gene mutation. Right: A threespine stickleback fish.

to investigate other species that evolved from four-legged ancestors but had since lost their legs, such as whales, snakes, and manatees. In 2006, he contacted manatee researcher Dr. Sentiel Rommel of the Florida Fish and Wildlife Research Institute, who had 114 manatee pelvic bones from autopsies that Kingsley could weigh. Almost all of these bones demonstrated a 10% increase in the weight of the left pelvic bone over the right. Fish, mice, and manatees all show the same legless, asymmetrical marks from the same single mutation in Pitx1. As manatees and stickleback fish are distinct species far apart in the evolutionary time chart, it seems unlikely that one gene would have arisen separately in the different species and then would develop the same mutation. A single gene was not thought to affect such a broad structural change as eliminating legs or pelvic fins because successful mutations tend to avoid pleiotropic genes, genes that affect many characteristics. In mice, Pitx1 mutations can lead to death because they fatally affect other mechanisms. In sticklebacks, mutated Pitx1 still fulfills its other functions, such as working in the thymus and olfactory organs, but it affects the pelvic regions. In these fish, the Pitx1 mutation is successful because only a portion of the mutant gene is expressed. Pitx1 is not alone Remarkably, Pitx1 is not the only gene that has affected the same changes across species that branched apart long ago. In the Proceedings of the National Academy of Sciences,

layout design: Ly Nguyen

Kingsley, along with Ecology and Evolution Professor Michael Bell from the State University of New York at Stony Brook and Assistant Biology Professor Michael Shapiro from the College of Science at the University of Utah, mentioned several other examples. One of these is a gene that determines sodium-channel resistance to neurotoxins in snakes and clams, species in different phyla. The same mutation is used for the same purpose in species that parted ways tens of millions of years ago. Despite the enormous number of genes and even larger number of possible mutations, a few genes can be responsible for the same changes in different species. More excitingly, a single gene can affect change in genetic lines that diverged long ago. S ERIKA WILLIAMS is a freshman considering a major in Science, Technology, and Society, with a minor in Psychology. In addition to writing about scientific discoveries, she enjoys classical music, tutoring, eating desserts, and hanging out with friends. To Learn More: Read the departmental website of Dr. David Kingsley: http://med. stanford.edu/profiles/David_Kingsley

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