Rees, Jasmin; (2023) The Role of Micronutrients in Genetic Adaptation. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis explores the role of micronutrients in genetic adaptation, largely focusing on micronutrients as the selective driver of local adaptation in modern humans. Additionally, the role of the micronutrient selenium in wider mammalian evolution is also investigated. Micronutrients are key dietary components in all organisms, needed in small, specific quantities and involved in a wide variety of essential metabolic processes. In modern humans, all micronutrients (with the exception of vitamin D) must be absorbed from the diet, since they cannot be synthesised within the body. Levels of dietary micronutrients in turn depend on the composition of the soil where plant and animal foodstuffs grow and feed, and hence can vary widely over different localities. As informed by a novel simulation framework, I use the allele-differentiation statistic F_ST and recently developed genealogical method Relate to identify signatures of natural selection in 40 diverse modern human populations in 276 genes associated with 13 micronutrients. I show signatures of positive selection are inferred in many global populations and micronutrient categories, and show that the strongest signatures of positive selection agree with known micronutrient composition of local soils and endemic deficiencies in modern human populations. I found no evidence for classic polygenic models of positive selection and infer that adaptation in response to micronutrients in the diet is most likely monogenic or oligogenic in nature. I evaluate the evidence for positive selection in genes associated with zinc, calcium, selenium, iron and iodine in detail and use a combination of methods to propose the origin and timing of selection acting on these micronutrient-associated genes. I propose that micronutrients are an important selective force in modern humans, and have shaped the genomic variation of our species. I also present the first evidence for molecular convergent evolution in mammalian proteins losing the selenium-containing amino acid selenocysteine for the sulphur-containing cysteine.

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