Comparative Genomics: Deciphering the Interplay Between Evolutionary History and Disease Susceptibility

Abstract Comparative genomics has emerged as a cornerstone of evolutionary ecology, providing a powerful framework for deciphering how historical evolutionary forces and ecological pressures shape genomic architecture, adaptation, and disease susceptibility across species. By systematically comparing genomes, this approach reveals patterns of gene conservation that underpin essential biological functions, alongside divergence events that drive evolutionary innovation and ecological specialization. Advances following the Human Genome Project have enabled high-resolution analyses of phylogenetic relationships, adaptive evolution, and horizontal gene transfer, offering deeper insight into how genomes respond to environmental and ecological constraints. This review synthesizes current evidence on the role of comparative genomics in elucidating adaptive evolution, host–pathogen co-evolution, and population-level variation in disease risk. We examine how genetic variation including single nucleotide polymorphisms, copy number variations, and structural variants modulates immune function and disease susceptibility, often reflecting evolutionary trade-offs shaped by past selective pressures. Model organisms such as Drosophila, zebrafish, and murine systems are highlighted as critical translational platforms for linking genomic variation to functional and pathological outcomes. The integration of evolutionary genomics with disease ecology is discussed in the context of applied biology, medicine, and public health. Insights from comparative genomics inform biodiversity conservation, personalized medicine, pharmacogenomics, and emerging therapeutic strategies, including genome editing technologies. Collectively, this work underscores the value of an evolutionary perspective in understanding genomic complexity, disease dynamics, and adaptive resilience across biological systems.