Disease-associated genetic mutations show that hydrophobicity defines functional protein segments

What is it about?

Proteins rely on the hydrophobic effect to maintain structure and interactions with their environment, yet natural selection on amino acid hydrophobicity has not been detected. Using genetic variant data from across the human genome and a new method to identify hydrophobic protein segments, we resolve this seeming inconsistency, finding that selection generally increases with the length of the unbroken hydrophobic sequence and mutations that change hydrophobic segments.

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Photo by PAUL SMITH on Unsplash

Photo by PAUL SMITH on Unsplash

Why is it important?

Given this new evidence that hydrophobic domains are generically functional, it means that hydrophobicity should be considered more explicitly when evaluating the impact of genetic mutations. These results could lead to improvements in a wide range of genomic tools as well as insights into protein-aggregation disease etiology. Moreover, since the method only requires protein sequence information, this approach may be used to examine the protein evolutionary history of hydrophobic domains.