Evidence of zoonotic pathogens through biophysically induced genomic variance.

Zoonoses are infectious agents that are transmissible between animals and humans. Up to 60% of known infectious diseases and 75% of emergent diseases are zoonotic. Genomic variation between homeostatic populations provides a novel window into the effect of environmental pathogens on allelic distributions within the populations. Genodynamics is a biophysical approach utilizing developed metrics on biallelic single-nucleotide polymorphisms (SNPs) that can be used to quantify the adaptive influences due to pathogens. A genomic free energy that is minimized when overall population health is optimized describes the influence of environmental agents upon genomic variation. A double-blind exploration of over 100 thousand SNPs searching for smooth functional dependencies upon four zoonotic pathogens carried by four possible hosts amidst populations that live in their ancestral environments has been conducted. Exemplars that infectious agents can have significant adaptive influence on human populations are presented. One discussed SNP is likely associated with both adaptive and innate immune regulation. The adaptive response of another SNP suggests an intriguing connection between zoonoses and human cancers. The adaptive forces of the presented pathogens upon the human genome have been quantified.

Quantification of adaptive forces on SNP rs1010211 due to viral zoonotic pathogens.

Widespread genotyping of human populations in environmental homeostasis has created opportunities to quantify how environmental parameters affect the genomic distribution of variants in healthy populations. This represents an ongoing natural experiment upon the human species that can only be understood through developing models of adaptation. By examining the information dynamics of optimal SNP distributions within such populations, "adaptive forces" on genomic variants can be quantified through comparisons between different populations. To this end, we are performing double-blind scans of SNPs in order to ascertain any potential smooth functional relationships between the frequencies of the variants and changes in quantified environmental parameters. At present, we have sequentially examined more than twenty thousand SNPs (on chromosome 3) of nine homeostatic native populations for potential adaptive flagging of the variants as functions of 15 environmental parameters. Our first significant flag has related rs1010211 to viral pathogens in mammalian hosts. Such pathogens present a significant risk for the emergence of new infectious diseases in humans. This genomic variant is within the gene TNIK, which is a germinal center kinase (GCK). GCKs are participants in both adaptive and innate immune regulation. However, the function of TNIK is not fully understood. We quantify the adaptive force on the C allele due to the pathogens as 0.04 GEU's/viral species.

Single Nucleotide Polymorphisms: A Window into the Informatics of the Living Genome.

Nested in the environment of the nucleus of the cell, the 23 sets of chromosomes that comprise the human genome function as one integrated whole system, orchestrating the expression of thousands of genes underlying the biological characteristics of the cell, individual and the species. The extraction of meaningful information from this complex data set depends crucially upon the lens through which the data are examined. We present a biophysical perspective on genomic information encoded in single nucleotide polymorphisms (SNPs), and introduce metrics for modeling information encoded in the genome. Information, like energy, is considered to be a conserved physical property of the universe. The information structured in SNPs describes the adaptation of a human population to a given environment. The maintained order measured by the information content is associated with entropies, energies, and other state variables for a dynamic system in homeostasis. "Genodynamics" characterizes the state variables for genomic populations that are stable under stochastic environmental stresses. The determination of allelic energies allows the parameterization of specific environmental influences upon individual alleles across populations. The environment drives population-based genome variation. From this vantage point, the genome is modeled as a complex, dynamic information system defined by patterns of SNP alleles and SNP haplotypes.

Development of genodynamic metrics for exploring the biophysics of DNA polymorphisms.

Single nucleotide polymorphisms (SNPs) represent an important type of dynamic sites within the human genome. These common variants often locally correlate within more complex multi-SNP haploblocks that are maintained throughout generations in a stable population. Information encoded in the structure of SNPs and SNP haploblock variation can be characterized through a normalized information content metric. Genodynamics is being developed as the analogous "thermodynamics" characterizing the state variables for genomic populations that are stable under stochastic environmental stresses. Since living systems have not been found to develop in the absence of environmental influences, this paper describes the analogous genomic free energy metrics in a given environment. SNP haploblocks were constructed by Haploview v4.2 for five chromosomes from phase III HapMap data, and the genomic state variables for each chromosome were calculated. An in silico analysis was performed on SNP haploblocks with the lowest genomic energy measures. Highly favorable genomic energy measures were found to correlate with highly conserved SNP haploblocks. Moreover, the most conserved haploblocks were associated with an evolutionarily conserved regulatory element and domain.