SEX at a molecular level is spawning an elite class of proteins. Maxygen, a company in Santa Clara, California, has used a DNA shuffling technique to create interferons that are dramatically more effective against viruses than any produced naturally by the immune system. It has also made ultra-efficient versions of an industrial enzyme.
When organisms reproduce sexually, the offspring end up with a mix-and-match set of genes inherited from both parents. Maxygen's technique is similar, except the parents are a series of related genes. These are cut into pieces, shuffled together and then assembled to form a new genetic generation. Some of these daughter genes can manufacture proteins that are much better at certain tasks than nature's originals. The best ones can be screened out and shuffled to produce whole lineages of superior descendants, in a process mimicking evolution by natural selection.
Maxygen's technique was described earlier this year in Nature (vol 391, p 288). Now its potential is beginning to be realised. The parent genes are first broken into fragments by shattering their DNA with ultrasound, or cutting them up with an enzyme called DNAse. They are reassembled into daughter genes, comprising fragments from several parents, using a variant of the DNA-building polymerase chain reaction. Short template or "primer" sequences ensure that the fragments are stitched together in the correct order to produce a functioning gene. The daughter genes can then be inserted into bacteria or fungi, where they begin making protein.
To make superior versions of an industrial enzyme, the identity of which
is still secret, Maxygen's scientists isolated genes from 26 microorganisms
which each make their own versions of the enzyme. Using its system of DNA
shuffling, Maxygen made 600 new daughter genes, 77 of which produced superior
enzymes. Screening showed up variants which functioned better than natural
enzymes at hi
Contact: Claire Bowles