How scientists redesign DNA codes

1. On a computer, start with the natural DNA sequence of the letters across a chromosome. 2. Tell the computer to make specific alterations, such as: — Every time it sees the letter series TAG at the end of a gene, change it to TAA. Both triplets deliver the same message to the yeast’s machinery for making protein, so the change doesn’t affect the yeast. But the TAG triplet could be used in a different place to make the yeast produce a protein from building blocks not found in nature, for example. — Delete a class of genes called ‘tRNA genes’ from their normal positions, where they can impair the process of duplicating the genome before a yeast cell divides. These genes will be relocated to their own, new chromosome, where they can do their jobs without causing trouble. — Insert bits of DNA code that will let researchers rearrange the order of genes on the chromosomes, like shuffling a deck of cards. This way, scientists can experiment with many different reshufflings to see which one makes yeast grow best, or perform best in some other way. 3. Once the alterations are done, break the redesigned code into lengths of about 10,000 letters apiece and have a company create chunks of DNA that reflect each of these segments. Chunks of that size can be easily manipulated in a laboratory. 4. In the test tube, use a chemical reaction to glue three to six of these chunks together into a “megachunk.” 5. Take ordinary yeast and use this 30,000-60,000-letter megachunk to replace the corresponding segment of natural DNA. Yeast will do this without much coaxing. 6. If the yeast doesn’t grow normally, identify and fix the problem in the megachunk. This is called debugging. If it’s fine, add the next megachunk. 7. Repeat steps 4-6 until the entire chromosome has been replaced with megachunks of synthetic DNA.