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The Stuff That Finches are Made of
A songbird's remarkable recovery from disease has scientists sequencing part of the finch genome
  
By Sharon Guynup


Featured Article.

In the summer of 1994, house finches started dying all across the state of Maryland. The tiny songbirds, which had been blinded by bacterial eye infections, could no longer see to find food. They were dying of starvation. During the next two years, the blinding infection radiated out from this epicenter, becoming an epidemic that affected approximately 60 percent of house finches in the Eastern United States. About 100 million birds died.


Healthy male house finch

But by the next summer, the infection seemed to have abated. Geoff Hill, an avian behavioral ecologist at Auburn University in Alabama noted that only 30 percent of the finches were sick in 1995, down from 60 percent the year before. Only 20 percent were afflicted in 1998. "It was a major wildlife disease, but today just a few birds are sick," he says. "What caused the disease to peter out?" And what caused it to occur with such devastation in the first place?

Hill wondered if the survivors had resistant genes in higher numbers than those that fell ill. So he teamed up with University of Washington evolutionary biologist Scott Edwards and Chris Hess, Edwards' doctoral student, to find out. In the process, they hoped to unearth new clues to how genes, disease, and immunity interact.

Edwards and Hess took bird watching to the molecular level. As a first step, they used shotgun sequencing to sequence a 32,000-base-pair region of the finch's genome. This is the longest genetic sequence yet of any songbird, a genetically little explored group, which includes over half of all bird species. Until now, avian genetic work has largely been confined to the barnyard, with the only large-scale work done on chickens. "We are not the human genome project," jokes Edwards. "This sequencing technique is very new for birds." Edwards and his colleagues published their study in a recent issue of Genome Research.

The researchers were hunting for a functional Mhc gene. This immune system gene is also found in humans and other animals, and is thought to be the most important gene for inherited immunity. They found a nonfunctional Mhc pseudogene embedded in the region they had sequenced but have yet to find a functional Mhc gene in the finches. "Once we find the Mhc, we'll compare its frequency in current bird populations with birds before the epidemic," says Edwards. Because Hill has done field studies on house finches for the past 12 years, his stored blood samples provide a genetic snapshot of these birds before, during, and after the disease hit. And because finch populations in the Western United States and Hawaii were not affected by this bacterial outbreak, genetic comparison can help determine whether Mhc genes were responsible for protecting finch populations on the East Coast after the initial disaster in 1994. "We want to catch natural selection in action," notes Edwards.


Finch afflicted with a bacterial eye infection

Natural selection may have been initiated by females in their mating choices. House finch males with the brightest red plumage are most in demand among the ladies, and healthy males boast the most brilliant feathers. A number of illnesses, including this eye disease, make male plumage dull, which limits their chances of finding a partner. Hill hopes genetic analysis will show whether the healthy Mhc gene turns males into Don Juans—ensuring that good genes are passed on to restore the health of the population. "The most exciting outcome would be to prove that females are ensuring the health of their offspring by choosing males with brilliant plumage."

In the next phase of the research, Hill will expose house finches to the blindness bacterium—Mycoplasma gallisepticum—and Edwards and Hess will examine the genetic differences between birds who get sick and those who don't. This may help identify genes affected by the epidemic—or those that now protect against infection.


within their cells people may share more with birds than scientists expected

This sequence also provided a pictorial analysis of the house finch's "genomic signature," the first of its kind for birds. Genomic signatures reveal some of the evolutionary forces acting on a particular genetic sequence—or the entire genome. They show patterns of gene mutation and gene repair, as well as patterns of natural selection.

Analysis of this new avian signature yielded some surprises. Deep within their cells people may share more with birds than scientists expected. Bird genomes are quite compact—possibly because of the high metabolic demands of flight. But "the number of genes in birds is probably not less than the number of genes in mammals," says Edwards. "We know genes are more closely spaced in birds. And there are few 'junk DNA' remnants: The genome is constantly being bombarded by foreign DNA in the same way the Earth is bombarded by asteroids." In mammals, this DNA proliferates, but much less so in birds. The result: the finch genome is about one-half the size of the human genome, or about 1.5 billion base pairs.

Three genes were found in the sequenced region, a rough equivalent of a mammalian Mhc region. The fragment was not as dense as the chicken Mhc sequence, which housed 20 genes in just 90,000 base pairs. "Paradoxically, the density of genes in the house finch is more similar to the mammal's Mhc than the chicken," said Edwards. "And unless we looked at an atypical region, not all birds are the same."

And all finches may not be the same. Edwards will be comparing populations before and after the epidemic with finches from Hawaii and the Western US—birds that were never exposed to the eye infection. He and his team hope to identify any obvious genetic differences and prove whether Mhc genes were involved in the birds' rebound. "We're hoping to nail down specific parts of the genome related to disease resistance," says Hill.

This is an early step towards answering questions about the evolution of species with molecular tools. "Gaining a better understanding of the evolution of disease and how vertebrate organisms and disease coevolve is very important," says Hill.

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Hess, C.M., Gasper, J., Hoekstra, H.E., Hill, C.E. & Edwards, S.V. MHC Class II pseudogene and genomic signature of a 32-kb cosmid in the house finch (Carpodacus mexicanus). Genome Res 10, 613-623 (May 2000).
 

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