This expansion might have a dual role in the evolution of the snake body plan because it no eliminates the expression boundaries that typically correlate with the site of forelimb outgrowth, and it results in similar Hox expression patterns in nearly all pre-sacral trunk segments [23]. Expansions and shifts in Hox expression domains are closely associated with shifts in vertebral identity [24,25], and the homomorphic vertebrae of snakes are likely due, to broadly overlapping domains of Hox expression that are typically more restricted in vertebrates with regionalized axial skeletons [23]. A whole genome assembly for the garter snake would allow unprecedented access to both the coding and well-characterized regulatory domains of the Hox clusters, thereby enabling both comparative genomic and experimental genetic studies of these important regions.

The sheer number of vertebrae in snakes represents another classic departure from other amniotes, a change that is due to an acceleration of the embryonic segmentation clock [26]. A complete snake genome would provide an opportunity to examine the conserved regulatory network that determines the pace of this clock, thereby allowing novel insights into a basic feature of segmented embryos. Gene expression assays and experimental embryology have implicated the Sonic Hedgehog (Shh) and Fibroblast Growth Factor (Fgf) pathways in the reduction of snake hindlimbs [23]. Studies of cetaceans show the involvement of these pathways in hindlimb reduction in mammals as well [27].

While it is clear that Shh and Fgfs contribute to the developmental basis of limb loss, we still lack information about the genetic changes that control this change. Limb loss occurs in many vertebrate lineages, and strongest genetic evidence for causal mutations comes from the stickleback fish [28]. In this case, the underlying mutations occur in the hindlimb-specific transcription factor Pitx1, not in the Shh or Fgf pathways; morphological evidence suggests that changes in similar genes might occur in other species as well [29]. Thus, the availability of the garter snake genome could help identify additional molecular correlates of limb loss, and test for modifications in genes and regulatory elements already known to play a role in limb outgrowth and patterning.

Reproductive physiology, sexual behavior, and seasonality Garter snakes are famous for their communal hibernacula and the mass mating balls that Brefeldin_A accompany spring emergence in northern populations. This habit has lead to in-depth studies of the environmental and endocrine controls of reproductive physiology and mating behavior. Both sexes have disassociated courtship behavior and hormonal cycles, with courtship occurring independent of seasonal changes in testosterone or estradiol [30-34].