Sometimes the best way to analyze a structure is to try to build it. This is what HHMI investigator Jack W. Szostak of the Massachusetts General Hospital in Boston decided to do 20 years ago, when he made the world's first yeast artificial chromosome (YAC) that lookedand actedpretty much like a natural one. His goal was to dissect the structure of chromosomes.
Almost immediately, Maynard Olson, who is now director of the University of Washington Genome Center, saw the potential of YACs as carriers of large chunks of alien DNA that could be reproduced and then mapped as part of the Human Genome Project. YACs soon became the workhorse of genome mapping in yeast and mammals.
"We then cottoned to this idea as an approach for human gene therapyto introduce a therapeutic gene on its own private chromosome," says Huntington Willard. His lab created the first human artificial chromosome (HAC) in 1997 with the help of thousands of DNA tandem repeats that mimicked a human centromere. And now he visualizes many more uses for HACs, quite unrelated to gene therapy (see main story).
Apparently, no self-respecting model organism can do without artificial chromosomes of its own any more. Because mouse centromeres are very different from human ones (although many mouse genes are almost identical to human genes), it is not so easy to create a mouse artificial chromosome (MAC). A MAC, however, is in the works.
Meanwhile, Daphne Preuss is making progress on a plant artificial chromosome but does not want to call it "PLAC"that sounds unpleasant, she thinks. She plans to name it AtAC for the plant's full name, Arabidopsis thaliana. Not to be outdone, the fly research community is making its own plans, and soon the artificial chromosomes' bubbling alphabet soup may include another newcomer, FAC.
this story in Acrobat PDF format.
Reprinted from the HHMI Bulletin,
December 2003, pages 12-17.
©2003 Howard Hughes Medical Institute