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See Inside Scientific American Volume 309, Issue 2

Seemingly Unimportant Mutations Can Foster Disease

Initially innocuous genetic changes known as neutral mutations may play a role in disorders ranging from the flu and bacterial infections to schizophrenia

Plotkin also envisages focusing on cryptic mutations for a different end: making new molecules useful for the biotechnology industry. Many scientists are trying to artificially evolve designer proteins that will do specific tasks. Typically they look for mutations that overtly alter proteins in ways that enhance their ability to do the chosen task. But it may be useful to look for the hidden neutral mutations that could make proteins more likely to acquire useful mutations. “Understanding the role of cryptic mutations in an evolving protein could help to improve some already very useful techniques for engineering enzymes,” Plotkin says.

Applications like these are just the beginning. In many ways the study of cryptic variation has been a metaphor for itself. Knowledge and interest in the field has been building up under the surface for a long time, largely hidden from view, only to be released by the influx of new technology. “We’re really at the tip of the iceberg,” Plotkin says.

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