As a living information and communications system,
the genome encodes patterns in single nucleotide polymorphisms (SNPs)
reflecting human adaptation that optimizes population survival in differing
environments. This paper mathematically models environmentally induced adaptive
forces that quantify changes in the distribution of SNP frequencies between
populations. We make direct connections between biophysical methods (e.g.
minimizing genomic free energy) and concepts in population genetics. Our
unbiased computer program scanned a large set of SNPs in the major
histocompatibility complex region and flagged an altitude dependency on a SNP
associated with response to oxygen
deprivation. The statistical power of our double-blind approach is
demonstrated in the flagging of mathematical functional correlations of SNP
information-based potentials in multiple populations with specific
environmental parameters. Furthermore, our approach provides insights for new
discoveries on the biology of common variants. This paper demonstrates the
power of biophysical modeling of population diversity for better understanding
genome-environment interactions in biological phenomenon.
Sachidanandam, R., Weissman, D., Schmidt, S.C., Kakol, J.M., Stein, L.D., Marth, G., et al. (2001) A Map of Human Genome Sequence Variation Containing 1.42 Million Single Nucleotide Polymorphisms. Nature, 409, 928-933.
Lindesay, J., Mason, T.E., Hercules, W. and Dunston, G.M. (2014) Development of Genodynamic Metrics Forexploring the Biophysics of DNA Polymorphisms. Journal of Computational Biology and Bioinformatics Research, 6, 1-14.
Lindesay, J., Mason, T.E., Ricks-Santi, L., Hercules, W., Kurian, P. and Dunston, G.M. (2012) A New Biophysical Metric for Interrogating the Information Content in Human Genome Sequence Variation: Proof of Concept. Journal of Computational Biology and Bioinformatics Research, 4, 15-22.
Herman, J.R., Krotkov, N., Celarier, N.E., Larko, D. and Labow, G. (1999) Distribution of UV Radiation at the Earth’s Surface from TOMS-Measured UV-Backscattered Radiances. Journal of Geophysical Research: Atmospheres, 104, 12059-12076.
Grocott, M.P.W., Martin, D.S., Levett, D.Z., McMorrow, R., Windsor, J. and Montgomery, H.E. (2009) Arterial Blood Gases and Oxygen Content in Climbers on Mount Everest. The New England Journal of Medicine, 360, 140-149.
Gerhardt, H., Golding, M., Fruttiger, M., Ruhrberg, C., Lundkvist, A., Abramson, A., et al. (2003) VEGF Guides Angiogenic Sprouting Utilizing Endothelial Tip Cell Filopedia. The Journal of Cell Biology, 161, 1163-1177.
Farve, C.J., Mancuso, M., Maas, K., McLean, J.W., Baluk, P. and McDonald, D.M. (2003) Expression of Genes Involved in Vascular Development and Angiogenesis in Endothelial Cells of Adult Lung. American Journal of Physiology-Heart and Circulatory Physiology, 285, H1917-H1938. https://doi.org/10.1152/ajpheart.00983.2002
Villa, N., Walker, L., Lindsell, C.E., Gasson, J., Iruela-Arispe, M.L. and Weinmaster, G. (2003) Vascular Expression of Notch Pathway Receptors and Ligands Is Restricted to Arterial Vessels. Mechanisms of Development, 108, 161-164.
Carlson, T.R., Yan, Y., Wu, X., Lam, M.T., Tang, G.L., Beverly, L.J., et al. (2005) Endothelial Expression of Constitutively Active Notch 4 Elicits Reversible Arteriovenousmal Formations in Adult Mice. Proceedings of the National Academy of Sciences of the United States of America, 102, 9884-9889.
Kim, Y.H., Hu, H., Guevara-Gallardo, S., Lam, M.T., Fong, S.Y. and Wang, R.A. (2008) Artery and Vein Size Is Balanced by Notch and Ephrin B2/EphB4 during Angiogenesis. Development, 135, 3755-3764. https://doi.org/10.1242/dev.022475