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The Role of Variant Accessibility in Influenza Virus Evolution

The influenza (flu) virus constantly evolves and adapts through acquiring new mutations. Scientists at St. Jude ChildrenÔÇÖs Research Hospital have conducted research to further understand why and how flu viruses change. Their findings have been published in Science Advances.

A Key Driver of Evolution: Variant Accessibility

Traditionally, mutations in viruses are viewed in terms of fitness, with the fittest variant emerging as the dominant strain in a population. However, the St. Jude team proposes an alternative principle called “variant accessibility.” This principle suggests that the accessibility of a mutation, rather than its fitness, is a key driver of evolution.

Assessing Mutational Accessibility

The research team, led by Dr. Alexander Gunnarsson and Dr. M. Madan Babu from the St. Jude Department of Structural Biology and Center of Excellence for Data-Driven Discovery, developed a model to predict how and why specific mutations emerge in a viral population. Their model focuses on the accessibility of a mutation, particularly in terms of how specific protein sites can be modified after acquiring a mutation.

Phosphorylation as a Case Study

The researchers used phosphorylation, the addition of a phosphate molecule to specific amino acids of a protein, as an example of a modification influenced by mutations. Phosphorylation plays a crucial role in the flu virus’s ability to infect host cells. By examining past influenza pandemics, the team gathered data to further develop their model.

Understanding Jackpot Events

The model also helped the researchers understand the concept of “jackpot events.” These events refer to mutations that occur early in a population’s growth and continue to provide benefits throughout the descendants. The more accessible a genotype is, the more frequent these jackpot events occur. This is because high accessibility increases the probability of acquiring specific mutations. Even if a mutation is less fit compared to others, its prevalence can increase massively if it is highly accessible.

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