New method identifies adaptive mutations in complex evolving populations

A team co-led by a scientist at the University of California, Riverside, has developed a method to study how HIV mutates to escape the immune system in multiple individuals, which could inform HIV vaccine design.

HIV, which can lead to AIDS, evolves rapidly and attacks the body’s immune system. Genetic mutations in the virus can prevent it from being eliminated by the immune system. While there is no effective cure for the virus currently available, it can be controlled with medication.

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“Understanding the genetic drivers of disease is important in the biomedical sciences,” said John P. Barton, an assistant professor of physics and astronomy at UCR, who co-led the study with Matthew R. McKay, a professor of electronic and computer engineering and chemical and biological engineering at the Hong Kong University of Science and Technology. “Being able to identify genomic rearrangements is key to understanding how illnesses occur and how to treat them.”

Barton explained that notable examples of genetic drivers of the disease include mutations that allow viruses to escape from immune control, while others confer drug resistance to bacteria.

“It can be difficult, however, to differentiate between real, adaptive mutations and random genetic variation,” he added. “The new method we developed allows us to identify such mutations in complex evolving populations.”

Evolutionary history, he added, contains information about which mutations affect survival and which simply reflect random variation.

“However, it is computationally difficult to extract this information from data,” he said. “We used methods from statistical physics to overcome this computational challenge. Our method can be applied generally to evolving populations and is not limited to HIV.”

McKay explained the new method provides a means to efficiently infer selection from observations of complex evolutionary histories.

“It enables us to sort out which genetic changes provide an evolutionary advantage from those that offer no advantage or have a deleterious effect,” he said. “The method is quite general and could be potentially used to study diverse evolutionary processes, such as the evolution of drug resistance of pathogens and the evolution of cancers. The accuracy and high efficiency of our approach enable the analysis of selection in complex evolutionary systems that were beyond the reach of existing methods.”

Some well-known diseases that have known genetic causes are cystic fibrosis, sickle cell anaemia, Duchenne muscular dystrophy, colourblindness, and Huntington’s disease.

“In the case of HIV, an understanding of the genetic mutations that lead to HIV resistance could help researchers determine the most appropriate treatment for patients,” Barton said. “Our approach isn't limited to HIV, but there are a few reasons why we focused on HIV as a test system. HIV is highly mutable and genetically diverse. It also mutates within humans to escape from the immune system. Understanding the details of how HIV evolves could therefore help to develop better treatments against the virus.”

Barton was supported by a grant from the National Institutes of Health. Study results appear in Nature Biotechnology. The title of the research paper is “MPL resolves genetic linkage in fitness inference from complex evolutionary histories.”

Source: UC Riverside