BAC to the Future?

Abstract

The emerging problems with YACs may have been a blow to many genome researchers, but some scientists have long been advocating more funding for alternative DNA carriers. As the Human Genome Project focused on YACs in recent years, however, support for the development of non-YAC systems has been hard to come by. But as the community comes to grips with the limitations of YACs, researchers are starting to take another look at the alternatives. One of the most promising is the newest-the Bacteria Artificial Chromosome (BAC). Like a YAC, it is formed by inserting foreign DNA into a microorganism - E. coli in the case of the BAC - and letting the organism's genetic reproduction machinery take over to make copies. Mel Simon and his group at Caltech developed the BAC in 1990 specifically to try to get around some of the problems with YACs, and Simon says they have ben at least partially successful. BACs don't appear to result in unrelated pieces of DNA being spliced together and cloned, for example, and very preliminary analysis suggests that deletion of stretches of DNA will not be a significant problem. Best of all, he says, those regions of the human genomemore » that are uncloneable in YACs will probably clone just fine in BACs, and vice-versa. BACs do, however, have one significant disadvantage: They can carry stretches of only 200,000 to 300,000 bases of foreign DNA - less than one-quarter as long as the best YACs. And other possible alternatives to YACs are limited to even shorter fragments. Another bacteria-based carrier known as a P1 can carry DNA insets of about 100,000 bases, and cosmids, which have been around the longest, are shorter yet - about 40,000 bases. While none of these systems is going to challenge the YAC for the size of their genome fragments, Simon says, they should provide a more precise complement to the YACs brute-force capabilities.« less