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

Mark D. Lucock; Patrice R. Jones; Martin Veysey; Rohith Thota; Manohar Garg; John Furst; Charlotte Martin; Zoe Yates; Christopher J. Scarlett; Nina G. Jablonski; George Chaplin; Emma L. Beckett

doi:10.1002/ajhb.23667

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

Mark D. Lucock^*
, Patrice R. Jones
, Martin Veysey
, Rohith Thota
, Manohar Garg
, John Furst
, Charlotte Martin
, Zoe Yates
, Christopher J. Scarlett
, Nina G. Jablonski
, George Chaplin
, Emma L. Beckett

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

Abstract

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 cross-sectional 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 D₃ were measured by immunoassay and HPLC, respectively. Results: 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 D₃ synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose–response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D₃ photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. 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. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D₃ synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D₃. Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

Original language	English
Article number	e23667
Number of pages	23
Journal	American Journal of Human Biology
Volume	34
Issue number	4
Early online date	21 Aug 2021
DOIs	https://doi.org/10.1002/ajhb.23667
Publication status	Published - Apr 2022
Externally published	Yes

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10.1002/ajhb.23667

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Lucock, M. D., Jones, P. R., Veysey, M., Thota, R., Garg, M., Furst, J., Martin, C., Yates, Z., Scarlett, C. J., Jablonski, N. G., Chaplin, G., & Beckett, E. L. (2022). Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation. American Journal of Human Biology, 34(4), Article e23667. https://doi.org/10.1002/ajhb.23667

@article{e84a184fc5544f459c46d4d7372750f1,

title = "Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation",

abstract = "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 cross-sectional 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 D3 were measured by immunoassay and HPLC, respectively. Results: 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 D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose–response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. 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. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0\% occurrence. The opposing, commonest (39\%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3. Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.",

author = "Lucock, \{Mark D.\} and Jones, \{Patrice R.\} and Martin Veysey and Rohith Thota and Manohar Garg and John Furst and Charlotte Martin and Zoe Yates and Scarlett, \{Christopher J.\} and Jablonski, \{Nina G.\} and George Chaplin and Beckett, \{Emma L.\}",

note = "Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC.",

year = "2022",

month = apr,

doi = "10.1002/ajhb.23667",

language = "English",

volume = "34",

journal = "American Journal of Human Biology",

issn = "1042-0533",

publisher = "Wiley-Liss Inc",

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Lucock, MD, Jones, PR, Veysey, M, Thota, R, Garg, M, Furst, J, Martin, C, Yates, Z, Scarlett, CJ, Jablonski, NG, Chaplin, G & Beckett, EL 2022, 'Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation', American Journal of Human Biology, vol. 34, no. 4, e23667. https://doi.org/10.1002/ajhb.23667

TY - JOUR

T1 - Biophysical evidence to support and extend the vitamin D-folate hypothesis as a paradigm for the evolution of human skin pigmentation

AU - Lucock, Mark D.

AU - Jones, Patrice R.

AU - Veysey, Martin

AU - Thota, Rohith

AU - Garg, Manohar

AU - Furst, John

AU - Martin, Charlotte

AU - Yates, Zoe

AU - Scarlett, Christopher J.

AU - Jablonski, Nina G.

AU - Chaplin, George

AU - Beckett, Emma L.

PY - 2022/4

Y1 - 2022/4

N2 - 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 cross-sectional 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 D3 were measured by immunoassay and HPLC, respectively. Results: 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 D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose–response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. 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. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3. Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

AB - 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 cross-sectional 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 D3 were measured by immunoassay and HPLC, respectively. Results: 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 D3 synthesis (reflected in both TOMS and seasonal data). UV-wavelength exhibits a dose–response relationship in folate loss within light skin IRF4-TT genotype (305 > 310 > 324 > 380 nm). Significant vitamin D3 photosynthesis only occurs within light skin HERC2-GG genotype, and is maximal at 305 nm. 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. Four genes (5xSNPs) influenced blood vitamin levels when stratified by pigmentation genotype; MTHFR-rs1801133/rs1801131, TS-rs34489327, CYP24A-rs17216707, and VDR-ApaI-rs7975232. Lightest IRF4-TT/darkest HERC2-AA genotype combination (greatest folate loss/lowest vitamin D3 synthesis) has 0% occurrence. The opposing, commonest (39%) compound genotype (darkest IRF4-CC/lightest HERC2-GG) permits least folate loss and greatest synthesis of vitamin D3. Conclusion: New biophysical evidence supports the vitamin D-folate hypothesis for evolution of skin pigmentation.

UR - https://www.scopus.com/pages/publications/85113169177

U2 - 10.1002/ajhb.23667

DO - 10.1002/ajhb.23667

M3 - Article

C2 - 34418235

AN - SCOPUS:85113169177

SN - 1042-0533

VL - 34

JO - American Journal of Human Biology

JF - American Journal of Human Biology

IS - 4

M1 - e23667

ER -

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

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