Homeotic and nonhomeotic patterns in the tetrapod vertebral formula

Vertebrate development and phylogeny are intimately connected through the vertebral formula, the numerical distribution of vertebrae along the body axis into different categories such as neck and chest. A key window into this relationship is through the conserved Hox gene clusters. Hox gene expression boundaries align with vertebral boundaries, and their manipulation in model organisms often results in the transformation of one vertebral type into its neighbor, a homeotic transformation. If the variety in the vertebrate body plan is produced by homeotic shifts, then the number of adjacent vertebrae will be inversely related when making interspecies comparisons since the gain in one vertebra is due to the loss in its neighbor. To date, such a pattern across species consistent with homeotic transitions has only been found in the thoracolumbar vertebral count of mammals. To further investigate potential homeotic relationships in other vertebrate classes and along the entire body axis, we compiled a comprehensive dataset of complete tetrapod vertebral formulas and systematically searched for patterns by analyzing combinations of vertebrae. We uncovered mammalian homeotic patterns and found balances between distal vertebrae not anticipated by a Hox-vertebral homeotic relationship, including one that emerged during the progression from theropods to birds. We also identified correlations between vertebral counts and intergenic distances in the HoxB gene cluster which do not align with the common picture of a colinear relationship between Hox expression and vertebral categories. This quantitative approach revises our expectations for the diversity of a Hox-mediated vertebrate body plan.