Vitamin-related phenotypic adaptation to exposomal factors: The folate-vitamin D-exposome triad

Lucock, Mark

doi:10.1016/j.mam.2021.100944

Cited by 8 publications

(19 citation statements)

References 135 publications

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“…For vitamin D, again only two genes ‐ CYP24A (rs17216707) and VDR‐ApaI (rs7975232) were relevant. CYP24A encodes cacidiol 24‐hydroxylase, which metabolizes calcidiol (plasma/transport form of vitamin D 3 ) to inactive D vitamers (Lucock, 2021), a process that is under tight feedback regulation to regulate calcium homeostasis. VDR‐ApaI is a polymorphism in the VDR gene.…”

Section: Discussionmentioning

confidence: 99%

“…All these factors need to be integrated into the evolutionary model to select a biologically appropriate combination that can maintain homeostasis in vitamin D and folate mediated one‐carbon metabolism. In this way, phenotype is calibrated to the UVR exposome (Lucock, 2021). Although further work is needed to better elucidate the relationship between these factors and human skin phototype, the current study moves the window of evidence forward, extending our ideas on human origins.…”

Section: Discussionmentioning

confidence: 99%

“…The vitamin D‐folate hypothesis represents one of the major theories explaining the evolution of human skin pigmentation (Jones, Lucock, Veysey, & Beckett, 2018; Lucock, 2021). Vitamin D and folate are metabolically and structurally discrete vitamins, but are linked in that they are both photosensitive.…”

Section: Introductionmentioning

confidence: 99%

“…When the VDR is activated by vitamin D, the nuclear receptor regulates calcium and phosphorus homeostasis, and promotes the growth and differentiation of several cell types that are found in VDR‐dependent target tissues (Bouillon et al, 2008). Studies have shown that 2276 genomic loci are occupied by the VDR with 229 genes exhibiting altered expression profiles in response to vitamin D. Others have shown similar vitamin D/VDR pleiotropy, and this has been reviewed by Lucock (2021).…”

Section: Introductionmentioning

confidence: 99%

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Biophysical evidence to support and extend the vitamin D‐folate hypothesis as a paradigm for the evolution of human skin pigmentation

Lucock

Jones

Veysey

et al. 2021

American J Hum Biol

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Objective: To test the "vitamin D-folate hypothesis for the evolution of human skin pigmentation."Methods: Total ozone mapping spectrometer (TOMS) satellite data were used to examine surface UV-irradiance in a large (n = 649) Australian crosssectional study population. Genetic analysis was used to score vitamin D-and folate-related gene polymorphisms (n = 22), along with two pigmentation gene variants (IRF4-rs12203592/HERC2-rs12913832). Red cell folate and vitamin D 3 were measured by immunoassay and HPLC, respectively.Results: i. Ultraviolet radiation (UVR) and pigmentation genes interact to modify blood vitamin levels; Light skin IRF4-TT genotype has greatest folate loss while light skin HERC2-GG genotype has greatest vitamin D 3 synthesis (reflected in both TOMS and seasonal data).ii. UV-wavelength exhibits a dose-response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D 3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm.iii. Three dietary antioxidants (vitamins C, E, and β-carotene) interact with UVR and pigmentation genes preventing oxidative loss of labile reduced folate vitamers, with greatest benefit in light skin IRF4-TT subjects. The putative photosensitiser, riboflavin, did not sensitize red cell folate to UVR and actually afforded protection. iv. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232.v. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D 3 synthesis) has 0% occurrence. The opposing,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biophysical evidence to support and extend the vitamin D‐folate hypothesis as a paradigm for the evolution of human skin pigmentation

Lucock

Jones

Veysey

et al. 2021

American J Hum Biol

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“…86,92,93 These will both help us tune future human biology to a changing world. 140,141 The final word has to be that human biology has a finite buffering capacity, and the current rate of environmental change means that our capacity for adaptive change and/or niche construction will be inadequate to permit survival if we don't address core issues now. DM will help define prognosis, but offers little hope for cure if the Anthropocene trajectory tracks along its current path for too much longer.…”

Section: Future Directionsmentioning

confidence: 99%

A Brief Introduction to Darwinian Medicine

Lucock¹

2022

Explor Res Hypothesis Med

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Darwinian/evolutionary medicine is a nascent, but rapidly developing field that applies the principles of evolutionary biology to help explain and prevent human disease. This article examines selected topics in Darwinian medicine, including diet-culture coevolution and health, developmental origins of health and disease, ageing (life history evolution and disease), nutrigenomics/pharmacogenomics, and the hygiene hypothesis (microbiota, pathogens and parasites within the Darwinian perspective of human health). It also looks at the future and how Darwinian medicine fits into anthropogenic changes at the planetary level. Although Darwinian medicine has a very broad domain, encompassing ageing, immunity, reproductive health, cancer, infectious disease, diet-culture interactions, the application of personalised medicine, the microbiome, and behavioural conditions, there are several core principles drawn from evolutionary biology that it applies, and which are integrated into this review. These include selection, drift, plasticity, mismatch, cultural practices, trade-offs, life history traits, antagonistic pleiotropy, heterozygote advantage, constraints, biologic defences, co-evolution (i.e., microbiome), adaptation/ maladaptation, novel environments, and the genome-phenome relationship.

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The evolution of human skin pigmentation: A changing medley of vitamins, genetic variability, and UV radiation during human expansion

Lucock

2022

American Journal of Biological Anthropology

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This review examines putative, yet likely critical evolutionary pressures contributing to human skin pigmentation and subsequently, depigmentation phenotypes. To achieve this, it provides a synthesis of ideas that frame contemporary thinking, without limiting the narrative to pigmentation genes alone. It examines how geography and hence the quality and quantity of UV exposure, pigmentation genes, diet-related genes, vitamins, anti-oxidant nutrients, and cultural practices intersect and interact to facilitate the evolution of human skin color. The article has a strong focus on the vitamin D-folate evolutionary model, with updates on the latest biophysical research findings to support this paradigm. This model is examined within a broad canvas that takes human expansion out of Africa and genetic architecture into account. A thorough discourse on the biology of melanization is provided (includes relationship to BH 4 and DNA damage repair), with the relevance of this to the UV sensitivity of folate and UV photosynthesis of vitamin D explained in detail, including the relevance of these vitamins to reproductive success. It explores whether we might be able to predict vitamin-related gene polymorphisms that pivot metabolism to the prevailing UVR exposome within the vitamin D-folate evolutionary hypothesis context. This is discussed in terms of a primary adaptive phenotype (pigmentation/depigmentation), a secondary adaptive phenotype (flexible metabolic phenotype based on vitamin-related gene polymorphism profile), and a tertiary adaptive strategy (dietary anti-oxidants to support the secondary adaptive phenotype). Finally, alternative evolutionary models for pigmentation are discussed, as are challenges to future research in this area.

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Vitamin-related phenotypic adaptation to exposomal factors: The folate-vitamin D-exposome triad

Cited by 8 publications

References 135 publications

Biophysical evidence to support and extend the vitamin D‐folate hypothesis as a paradigm for the evolution of human skin pigmentation

Biophysical evidence to support and extend the vitamin D‐folate hypothesis as a paradigm for the evolution of human skin pigmentation

A Brief Introduction to Darwinian Medicine

The evolution of human skin pigmentation: A changing medley of vitamins, genetic variability, and UV radiation during human expansion

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