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This month's focus: UF Center for Smell and Taste Center for Forensic Anthropology Analytical Chemistry at UF Dean's Musings Around the College Bookbeat Grants CLASnotes CLASnotes |
Demystifying DNA
In the race to sequence the human genome, scientists all over the world are busy mapping out the 75,000 genes encoded in our DNA. These genes dictate the production of proteins, which, as chains of 20 amino acids, can be mapped and stored as strings of letters in a computer. Thanks to sophisticated new research, we can now understand genes, once the mysterious building blocks of the human species, as complicated combinations of chemicals.
"Our challenge now," he continues, "is to convert these strings of chemical notation into data relevant to biologists. To do this, we are trying to understand how we can interpret chemical behavior and biological systems of genes in light of their evolutionary past." Here's where the pigs come in. When Institute of Food and Agriculture Sciences (IFAS) professors Rosalia and Frank Simmen discovered that pigs have three genes for making estrogen (instead of one), they came to Benner to help them figure out why. Benner conducted a chemical genealogy of sorts, building an "evolutionary tree" to trace the pig protein back to its early ancestors. "If we go back in time we can actually date when those extra genes emerged--about 25 million years ago," he says. "This is also the period when pigs began having litters of multiple young."
Benner and his research group are in hot demand, and not just from IFAS. "We have been working with HIV reverse transcriptases and proteases and the 'obesity gene protein,' leptin, and there are evolutionary stories in all of these protein families, which, placed in their historical contexts, all of a sudden talk to you and tell you the meaning and role of disease."
Benner's partnership with UF's medical and agricultural researchers is a prime example of the interdisciplinary nature of the brand new UF Genetics Institute. And Benner points out that CLAS adds the kind of fundamental science to the mix that is the basis of all technological advancement. "I'm doing basic science. I have not cured a disease. But every modern approach to the treatment of disease is associated with a better understanding of what it is that you're trying to treat. In the medical school, they have a very easily defined technological goal: they want to cure disease by introducing genes whose absence creates the diseased state. When you formulate a problem from this technological perspective you are saying, 'What can it do? Can I sell it?' From the scientific perspective, like much of what we do in the Liberal Arts and Sciences, the question is instead, 'What do I understand?'" "Unfortunately, it's more difficult to evaluate basic science. If you say you're going to cure the common cold," explains Benner, "we can appreciate that and know roughly what it's worth to us and to society, but if you say you're going to understand the history of the biosphere, we can't really evaluate or quantify that." Despite this, Benner emphasizes that basic research is always more powerful than applied technology (which is only relevant to what you apply it to). "Basic research, when done correctly, can in principle grow and grow and grow for decades. The discovery generations ago of gallium and germanium, two of the 90 naturally occurring chemical elements, eventually led to the creation of the semiconductor and the computer, but who could have known that at the time?" While the Genetics Institute is not a physical reality yet (the proposed $40 million, five-story ultra high-tech facility should be operational by 2004), a diverse array of groundbreaking genetics-related work is already being conducted across the UF campus. With contributing faculty not just in chemistry but also in biostatistics, zoology, mathematics, botany and anthropology, CLAS is one of the new Institute's key players.
"Furthermore, CLAS includes the internationally renowned Pound Human Identification Laboratory, directed by anthropologist Anthony Falsetti. This facility has been involved in numerous high-profile forensic cases for law enforcement and other government agencies and will become involved in more and more DNA work (particularly DNA fingerprinting and profiling) in the near future." Liberal Arts and Sciences mathematicians and statisticians are also involved in computational and analytical research designed to maximize the information available from the swelling databases of molecular and genetic knowledge. Miyamoto emphasizes that beyond the hard sciences, CLAS also covers the philosophical, historical, and social implications of modern genetics. "Genetics has grown to be so important to society at large that such contributions may become some of our most unique and important to the new Institute," he says. "In short, thanks to its rich diversity, outstanding faculty, and excellent students, CLAS will remain critical to the Institute in unifying disciplines from around the entire University." --Jane Gibson
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What do prehistoric pigs have to do with cutting edge research in genetics? Plenty, says CLAS chemist Steve Benner, who investigates many genetic-based questions, including the role of genes in life, present and past.
In other words, says Benner, all modern genetic study boils down to organic chemistry. "Scientists are out there sequencing whole organisms. They've done worms and bacteria and yeasts and are working on man. The minute we complete the genomic sequence for humans we have a chemical structure--an exact description of the material we pass on to our children.
By combining this chemical/genetic family history with associated paleontology (fossils) and physiological information from the Simmens, a story emerges. Apparently, after the cold, ecologically trying times of the Oligocene Period (around 30 million years ago), which many species did not survive, the warmer climate of the Miocene brought new semi-tropical forests to Europe. The new foliage may have provided pigs a sheltered habitat, allowing them for the first time to birth multiple young (by nature less ambulatory at birth than the more mature single young generally born in open savanna habitat) and to hide and protect these young until they became more self-sufficient. "The bottom line," says Benner, "is that these genes evolved in response to a changing climate to allow the pig to take on a new reproductive physiology. By correlating molecular events and reconstructing them in an evolutionary context, we can put together a story of function which converts these strings of letters into something that has meaning to a biologist."
As many human diseases are associated with heredity, medical scientists are scrambling to tie each illness to a change in one of our 75,000 genetically-dictated protein strings. A bit like looking for a needle in a haystack, but Benner's group can help simplify the process. "We use our evolutionary knowledge to tell technologists, 'Oh yeah, this protein is associated with pig reproductive strategy, not with immunosuppression,' to cut down their margin of trial and error in the hunting process."
"In Liberal Arts and Sciences, it is our diverse research and teaching across the field of genetics that is our strength and that ensures our major place in the Institute," explains zoologist Mike Miyamoto, the CLAS liaison to the Genetics Institute. Miyamoto, who himself is using DNA and protein sequences to trace the evolutionary history of humans and other mammals, stresses the diversity CLAS brings to the genetics table. His fellow zoologist Marta Wayne is investigating the genetic and environmental forces underlying major phenotypic traits, such as anatomical, behavioral, and ecological features. Additionally, CLAS faculty in Botany who work in plant genetics (and groups like Benner's in chemistry) are using the tools of modern molecular biology such as DNA amplification and sequencing to investigate how the genomes of humans and other species function, to assess their biological significance, and to better understand the historical factors that have shaped their evolution.
"CLAS also has anthropologists who are studying human genetic variation that is the underlying basis of disease susceptibility and resistance, drug responsiveness, and the like," continues Miyamoto. "Indeed, the Chair of the North American Committee of the Human Genome Diversity Project is our own anthropology professor John Moore.