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Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World

Daniel N. Harris, Ingo Ruczinski, Lisa R. Yanek, Lewis C. Becker, Diane M. Becker, Heinner Guio, Tao Cui, Floyd H. Chilton, Rasika A. Mathias, Timothy D. O’Connor
doi: https://doi.org/10.1101/175067
Daniel N. Harris
1Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD
2Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD
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Ingo Ruczinski
4Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore MD
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Lisa R. Yanek
5GeneSTAR Research Program, Johns Hopkins University School of Medicine. Baltimore, MD 21287
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Lewis C. Becker
5GeneSTAR Research Program, Johns Hopkins University School of Medicine. Baltimore, MD 21287
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Diane M. Becker
5GeneSTAR Research Program, Johns Hopkins University School of Medicine. Baltimore, MD 21287
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Heinner Guio
6Laboratorio de Biología Molecular, Instituto Nacional de Salud, Lima, Perú
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Tao Cui
7Department of Urology, Wake Forest School of Medicine, Winston-Salem, NC
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Floyd H. Chilton
8Department of Physiology/Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC
9Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC
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Rasika A. Mathias
5GeneSTAR Research Program, Johns Hopkins University School of Medicine. Baltimore, MD 21287
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Timothy D. O’Connor
1Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD
2Department of Medicine, University of Maryland School of Medicine, Baltimore, MD
3Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD
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Abstract

Background The metabolic conversion of dietary omega-3 and omega-6 18 carbon (18C) to long chain (> 20 carbon) polyunsaturated fatty acids (LC-PUFAs) is vital for human life. Fatty acid desaturase (FADS) 1 and 2 catalyze the rate-limiting steps in the biosynthesis of LC-PUFAs. The FADS region contains two haplotypes; ancestral and derived, where the derived haplotypes are associated with more efficient LC-PUFA biosynthesis and is nearly fixed in Africa. In addition, Native American populations appear to be nearly fixed for the lesser efficient ancestral haplotype, which could be a public health problem due to associated low LC-PUFA levels, while Eurasia is polymorphic. This haplotype frequency distribution is suggestive of archaic re-introduction of the ancestral haplotype to non-African populations or ancient polymorphism with differential selection patterns across the globe. Therefore, we tested the FADS region for archaic introgression or ancient polymorphism. We specifically addressed the genetic architecture of the FADS region in Native American populations to better understand this potential public health impact.

Results We confirmed Native American ancestry is nearly fixed for the ancestral haplotype and is under positive selection. The ancestral haplotype frequency is also correlated to Siberian populations’ geographic location further suggesting the ancestral haplotype’ s role in cold weather adaptation and leading to the high haplotype frequency within Native American populations’. We also find that the Neanderthal is more closely related to the derived haplotypes while the Denisovan clusters closer to the ancestral haplotypes. In addition, the derived haplotypes have a time to the most recent common ancestor of 688,474 years ago which is within the range of the modern-archaic hominin divergence.

Conclusions These results support an ancient polymorphism forming in the FADS gene region with differential selection pressures acting on the derived and ancestral haplotypes due to the old age of the derived haplotypes and the ancestral haplotype being under positive selection in Native American ancestry populations. Further, the near fixation of the less efficient ancestral haplotype in Native American ancestry suggests the need for future studies to explore the potential health risk of associated low LC-PUFA levels in Native American ancestry populations.

  • Abbreviations

    ALA =
    α–linolenic acid
    ARA =
    arachidonic acid
    C =
    carbon
    CI =
    confidence interval
    DHA =
    docosahexaenoic acid
    DPA =
    docosapentaenoic acid
    EPA =
    eicosapentaenoic acid
    FADS =
    fatty acid desaturase
    LA =
    linoleic acid
    LC =
    long chain
    MWD =
    modern western diet
    n3 =
    omega-3
    n6 =
    omega-6
    PUFA =
    polyunsaturated fatty acid
    TMRCA =
    time to the most recent common ancestor
    ya =
    years ago
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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    Posted August 10, 2017.
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    Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World
    Daniel N. Harris, Ingo Ruczinski, Lisa R. Yanek, Lewis C. Becker, Diane M. Becker, Heinner Guio, Tao Cui, Floyd H. Chilton, Rasika A. Mathias, Timothy D. O’Connor
    bioRxiv 175067; doi: https://doi.org/10.1101/175067
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    Evolution of Hominin Polyunsaturated Fatty Acid Metabolism: From Africa to the New World
    Daniel N. Harris, Ingo Ruczinski, Lisa R. Yanek, Lewis C. Becker, Diane M. Becker, Heinner Guio, Tao Cui, Floyd H. Chilton, Rasika A. Mathias, Timothy D. O’Connor
    bioRxiv 175067; doi: https://doi.org/10.1101/175067

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