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Clyde A. Hutchison III

MOLECULAR GENETICS

Research Interests

This laboratory has carried out investigations on biological systems ranging from bacteriophage to mice. The unifying theme has been a continuing search for improved methods to learn about gene function from DNA sequence information. We have been involved in genomics since before the advent of modern DNA sequencing. Clyde and Marshall Edgell dissected the genome of phage phiX174 with restriction enzymes in the 1970's, and Clyde was a member of the team in Fred Sanger's lab that sequenced the phiX174 genome; the first DNA molecule completely sequenced. Since that time we have been interested in a variety of problems in viral, bacterial, and mammalian genomics. Current projects include the following:

Bacterial Genomics. We began to analyze the chromosome of Mycoplasma genitalium by DNA sequencing in 1990. This is the smallest chromosome known for any autonomously replicating cell.We then collaborated with Ken Bott and Ed Hu at UNC, and Claire Fraser, Craig Venter and others at The Institute for Genomic Research (TIGR) to analyze the complete DNA sequence of the M. genitalium genome.  We have since become involved in collaboration with colleagues at TIGR to define the essential gene complement for a minimal cell. The Hutchison lab is also responsible for one component of the Berkeley Structural Genomics Center. This goal of this Center is to determine a complete set of structures for the gene products of a cell, based upon mycoplasma as a model for the minimal cell. Our role in the Center is to develop methods for assigning cellular functions to the protein structures.
Synthetic Genomics.  Over the past 30 years our ability to sequence DNA has greatly outstripped our capability to chemically synthesize DNA. We are interested in developing methods to close this "synthesis gap". Recently we have collaborated with Ham Smith, Cynthia Pfannkoch, and Craig Venter at IBEA (Institute for Biological Energy Alternatives) to work on improved methods for the assembly of large DNA from chemically synthesized oligonucleotides. We have proven these methods by assembling a  synthetic bacteriophage phiX174 genome. Further refinements should allow us to produce synthetic cellular genomes.
The L1 retroposon in mammals. In collaboration with Marshall Edgell we have characterized the LINES-1 (L1) retroposon. This is the major family of transposable elements in mammals, comprising more than 10% of the genome. We are now studying the function and evolution of the element. We have been able to estimate the ages of individual L1 insertions in the mouse genome by phylogenetic analysis. We are currently using the presence or absence of an L1 insertion at specific chromosomal sites as polymorphic markers, to resolve unanswered questions about recent mouse evolution.
Directed mutagenesis. One way to explore gene function is to use DNA sequence as the basis for designing mutations. We have developed methods for "complete mutagenesis" that allow the construction and analysis of single amino acid replacements at each codon within a gene. More recently we are interpreting our mutational data using three dimensional protein structures, to identify key interactions required for protein function and stability. We have applied these techniques to study enzymes encoded by the AIDS virus, HIV1. Current work focuses on identification of residues critical for function, stability, and dimerization of the HIV 1 reverse transcriptase.

Selected Publications

For more information, send email to Clyde Hutchison.

Last updated January 18, 2004.