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UTHSC Prof. Focuses Research Career on One Protein Family in Quest to Understand Evolution of Life

Dr. David Nelson’s research career has focused on one family of proteins, Cytochrome P450. He has established himself as an expert in naming or annotating new sequences in this family as they are uncovered. (Photo by Peggy Reisser/UTHSC)

Professor David Nelson was a member of an international team of researchers whose work was recently featured on the front cover of Nature. It is not the first time his research has contributed to front-page-worthy reports. In fact, several framed covers of prestigious journals that include his work line the walls behind his desk at the University of Tennessee Health Science Center.

A professor in the Department of Microbiology, Immunology and Biochemistry in the College of Medicine at UTHSC, Dr. Nelson has spent more than 30 years teasing out the secrets of one family of proteins, Cytochrome P450, to help the world understand its essential role in plant and animal evolution and life.

Get this PhD biochemist talking about the super family of genes that may eventually reveal more than 1 million sequences. It is his pursuit, his professional puzzle, his passion.

Cytochrome P450 (CYP 450) is essential in metabolizing or detoxifying various substances in the body, including certain drugs. Humans contain a small number of them, 57, plants and other organisms many more.

“The whole planet would be different if we didn’t have CYP 450s,” he said. The exploding scientific movement for sequencing genomes of various species to better understand their origins is fueling Dr. Nelson’s career-long interest.

“If you sequence them all (genomes), you get a much different picture of the evolution of the planet. You have the ability to reconstruct the history of life and how it has changed since the first cell existed,” he said. “That’s what motivates me. I’m very interested in that question. But I’m focusing on that one family.”

Dr. Nelson has become a go-to guy for annotating or naming sequences in this gene family as they are discovered. In addition to his duties as course director for the graduate courses in bioinformatics and biochemistry, he is called upon by scientists from all over the globe to name new CYP 450 sequences as they are sussed out by gene sequencing enterprises.

Annotation involves a complex series of letters and numbers built one after the other upon nomenclature for previously discovered sequences. He started focusing on naming CYP 450 back in 1985 as a postdoctoral fellow in Houston. Only 35 sequences of the family had been found. Since then, Dr. Nelson has become recognized as expert in this nomenclature.

“I’ve named about 80,000,” he said. “Every few days, I get a request from people saying, ‘Can you name these for me?’ It’s important to have names, because you can’t communicate effectively between laboratories if you don’t have names. It’s like speaking different languages.”

To date, there are 28,531 named P450s in the plant family. A factor that is reflected in the paper that was featured in Nature in late October. Dr. Nelson was one of 194 authors who contributed to a 10-year project, “The One Thousand Plant Transcriptomes Initiative,” which investigated genetic diversity in plant life. Researcher Gane Ka-Shu Wong, PhD, from Alberta, Canada, organized an international effort to sequence more than 1,000 plant transcriptomes (the gene sequence readouts or transcripts in a cell) and analyze the resulting data.

Dr. Nelson’s job was to work on the CYP 450 genes, extracting the sequences from the data collected and comparing them to already named P450s, thereby presenting a comprehensive picture across various stages in the evolution of plants. 

“Humans are just one species on the planet. I’m interested in the whole story,” Dr. Nelson said. “I am interested in developing a framework for understanding this family. I would like to be able to say I have identified all the families within the super family.”

Dr. Nelson said he is driven by the desire to understand life in infinite detail.

“I’m interested in the evolution of life and CYP 450 is my entree into this,” he said. “I can do this, and I can take it back to the first bacterial P450 that ever existed. I can try to reconstruct the history of what’s happened. I want to get to the point where I can see all the details about the evolution of this family and how that fits into life on the planet.”

Dr. Nelson is not the only scientist with this narrow focus on an expansive target. “There’s a group of people around the world who are into CYP 450 and we meet every couple of years.” he said. “A couple hundred people come together at these conferences. Everybody is like me.”