The complete set of genetic information in an organism, including all genes and non-coding sequences. Humans have 2 sets of 23 chromosomes containing approximately 21,787 protein-coding genes, with only 1-2% of the genome consisting of coding DNA while 98% is non-coding (including 3% regulatory elements like promoters and enhancers).
The genome functions through: (1) Gene expression—DNA is transcribed to mRNA, which is translated to proteins, (2) Epigenetic regulation—methylation and histone modifications control which genes are active without changing DNA sequence, (3) Regulatory elements—promoters, enhancers, silencers in non-coding regions control gene expression spatially and temporally, (4) Evolution—mutations, duplications, deletions create genetic variation upon which natural selection acts. The genome is NOT static—it's dynamically regulated by environmental signals (nutrients, hormones, stress) through epigenetic mechanisms. Only ~1-2% codes for proteins; the remaining 98% includes regulatory sequences, transposable elements, and structural RNAs. The genome has evolved over millions of years under specific environmental pressures; modern environmental mismatches (novel diet, sedentarism, chronic stress) create disease because gene expression patterns optimized for ancestral conditions are inappropriate for current environments.
Understanding the genome from an evolutionary medicine perspective is foundational to cPNI. The genome expects specific environmental inputs (periodic caloric restriction, high physical activity, variable nutrient density, seasonal photoperiods, intermittent fasting, cold/heat exposure) but receives mismatched signals in modern life (constant food availability, sedentarism, artificial light, chronic stress). This mismatch between genome expectations and environmental reality drives chronic disease. Rather than blaming 'bad genes,' cPNI focuses on restoring the environmental conditions the genome evolved to expect—using lifestyle interventions to create gene expression patterns consistent with health.
- Humans have 2 Ă— 23 chromosomes containing ~21,787 protein-coding genes
- Only 1-2% of genome codes for proteins; 98% is non-coding DNA
- 3% of non-coding DNA consists of regulatory elements (promoters, enhancers)
- Genome evolved over millions of years under specific environmental pressures
- Modern environmental mismatch creates inappropriate gene expression patterns
- Epigenetic modifications allow environmental signals to regulate gene expression
- Genome expects periodic caloric restriction, high activity, seasonal variation
- Chronic disease results from mismatch between genome and modern environment
- Single nucleotide polymorphisms (SNPs) create individual genetic variation
- epigenetics — modifications that regulate genome expression without changing DNA sequence
- gene expression — process by which genome information is used to synthesize proteins
- evolutionary mismatch — disease results when modern environment doesn't match genome expectations
- evolution — natural selection shapes genome over millions of years
- chromosomes — structures containing packaged genome DNA
- DNA methylation — epigenetic mechanism regulating genome gene expression
- genes — functional units within genome encoding proteins
- mutations — changes in genome sequence creating genetic variation
- SNPs — single nucleotide polymorphisms creating individual genome variation
- caloric restriction — environmental condition genome evolved to expect periodically
- physical activity — high levels expected by genome, now mismatched in modern sedentarism
- circadian rhythm — genome expects seasonal photoperiod variation, disrupted by artificial light
- intermittent fasting — feeding pattern genome evolved to expect, absent in modern constant food access
- stress — chronic stress creates genome expression patterns inconsistent with health
- transcription — process by which genome DNA is copied to RNA
- promoters — regulatory genome regions controlling gene transcription initiation
- enhancers — distal regulatory genome elements increasing gene expression
- natural selection — evolutionary force that shaped genome adaptations
- environmental signals — nutrients, hormones, stress that regulate genome expression epigenetically
- chronic disease — results from mismatch between genome expectations and modern environment