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Clyde Hutchison

Distinguished Professor, The J. Craig Venter Institute
Kenan Professor Emeritus, University of North Carolina at Chapel Hill

Hutchison is Distinguished Professor at the J. Craig Venter Institute in La Jolla, California, where he is a member of the Synthetic Biology Group. He is also a consultant for Synthetic Genomics, Inc. In 1995 he was elected to membership in the National Academy of Sciences. He graduated from Yale University in 1960, with a B.S. degree in Physics. His graduate studies were in the laboratory of Robert L. Sinsheimer at Cal Tech where he finished his Ph.D. in 1968. He was a member of the faculty of The University of North Carolina at Chapel Hill from 1968 until 2005, where he now holds the title Kenan Professor Emeritus. He has worked on the molecular genetics of bacteriophage, bacteria, and mammals. In Fred Sanger's lab (1975-6) he helped determine the first complete sequence of a DNA molecule (phiX174). He developed site-directed mutagenesis with Michael Smith (1978). In 1990 he began work with mycoplasmas as models for the minimal cell. This led to collaboration with Smith and Venter, and his current work on synthetic genomics.


"Design, Construction, and Analysis of a Minimal Bacterial Cell"

We used whole-genome design and complete chemical synthesis to minimize the 1079–kilobase pair synthetic genome of Mycoplasma mycoides JCVI-syn1.0. An initial design, based on collective knowledge of molecular biology combined with limited transposon mutagenesis data, failed to produce a viable cell. Improved transposon mutagenesis methods revealed a class of quasi-essential genes that are needed for robust growth, explaining the failure of our initial design. Three cycles of design, synthesis, and testing, with retention of quasi-essential genes, produced JCVI-syn3.0 (531 kilobase pairs, 473 genes), which has a genome smaller than that of any autonomously replicating cell found in nature. JCVI-syn3.0 retains almost all genes involved in the synthesis and processing of macromolecules. Unexpectedly, it also contains 149 genes with unknown or poorly defined biological functions. Progress in defining the functions of these genes will be discussed. JCVI-syn3.0 is a versatile platform for investigating the core functions of life and for exploring whole-genome design.

Clyde Hutchison