The evolutionary origin of snakes involved extensive morphological and physiological adaptations that included the loss of limbs, lung reduction, and trunk and organ elongation. Most snakes also evolved a suite of radical adaptations to consume large prey relative to their body size, including the ability to endure extreme physiological and metabolic fluctuations [1, 2] and produce diverse venom proteins [3, 4]. These radical adaptations, centered around consuming large prey whole, have made snakes an interesting model for studying metabolic flux and organ physiology, regeneration, and regulation, with the most important example being the Burmese python.
Within 2 to 3 days after feeding, the Burmese python (Python molurus bivittatus) can experience tremendous physiological changes, including: a 44-fold increase in metabolic rate (the highest among tetrapods); 35 to 100% increases in the mass of the heart, liver, pancreas, small intestine, and kidneys; 160-fold increase in plasma fatty acid and triglyceride content; and 5-fold increase in intestinal microvillus length [1, 5]. After the completion of digestion, each of these phenotypes is reversed as digestive functions are downregulated and tissues undergo atrophy . This extreme modulation of tissue morphology and function facilitates investigation into the signaling and cellular mechanisms that underlie regulation of organ performance and regeneration. These animals are also readily obtained from commercial breeders, non-aggressive, and easier and cheaper to care for than laboratory rats. The scientific potential of this system to reveal molecular mechanisms associated with these extreme reactions (and their reversal) is tremendous, and can provide novel insight into vertebrate gene and systems function, novel strategies and drug targets for treating human diseases, and alternative disease models.
Snakes have also been used as model species for high-profile discoveries pertaining to vertebrate development, including the findings that vertebrate metamerism (somitogenesis) can be controlled by changing the rate of somitogenesis , that the loss of limbs correlates with changes in expression of some regulatory genes  as well as Hox gene expression and gene structure , that particular developmental pathways are associated with tooth and fang development , and that limblessness in snakes may result from failure to activate core vertebrate signaling pathways during development and from changes in Hox gene expression [8, 11]. Snakes are also important models for high-performance muscle physiology , genetic sex determination , evolutionary ecology [14, 15], and molecular evolution and adaptation [16–18]. Enhanced snake genomic resources (eventually including comparative genomic data from multiple species) are expected to provide additional insight into how the unique structures and developmental processes of snakes evolved.
In addition to the python (which is non-venomous), venomous snake species are also important for biomedical research, as is developing a greater understanding of the genomic and adaptive contexts leading to the origin of venom genes. Worldwide, the World Health Organization estimates that there are about 2.5 million venomous snake bites per year (about 1,400 in the US), resulting in about 125,000 deaths . As a consequence, the health relevance of snake venom research is extensive. Genes identified in snake venoms are related to genes used in normal housekeeping and digestive roles in other vertebrates [3, 4], but the details of how these have been modified by evolution to become functionally diverse toxic venoms cannot readily be determined without good comparative information from the full complement of genes from both venomous and non-venomous snakes.