Approximation to the Distribution of Fitness Effects across Functional Categories in Human Segregating Polymorphisms

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The relative frequencies of polymorphic mutations that are deleterious, nearly neutral and neutral is traditionally called the distribution of fitness effects (DFE). Obtaining an accurate approximation to this distribution in humans can help us understand the nature of disease and the mechanisms by which variation is maintained in the genome. Previous methods to approximate this distribution have relied on fitting the DFE of new mutations to a single probability distribution, like a normal or an exponential distribution. Generally, these methods also assume that a particular category of mutations, like synonymous changes, can be assumed to be neutral or nearly neutral. Here, we provide a novel method designed to reflect the strength of negative selection operating on any segregating site in the human genome. We use a maximum likelihood mapping approach to fit these scores to a scale of neutral and negative fitness coefficients. Finally, we compare the shape of the DFEs we obtain from this mapping for different types of functional categories. We observe the distribution of polymorphisms has a strong peak at neutrality, as well as a second peak of deleterious effects when restricting to nonsynonymous polymorphisms.

Vyšlo v časopise: Approximation to the Distribution of Fitness Effects across Functional Categories in Human Segregating Polymorphisms. PLoS Genet 10(11): e32767. doi:10.1371/journal.pgen.1004697
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004697

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