were modified in diverse, interesting ways. For example, they evolved regulatory sequences that allowed them to be clustered at the axon initial segment and at Nodes of Ranvier in myelinated axons. Additional modifications evolved after the ancestral Na-v gene was duplicated, once near the origin of vertebrates and then again (repeatedly) in several vertebrate lineages. One of the most interesting Na-v modifications is the evolution of resistance to TTX, which typically blocks Na-v channels, in pufferfishes and other species that use TTX to ward off predators.
Glenn Northcutt analyzes, in Chapter 3, when and in which lineages complex brains evolved. Favoring a cladistic approach, Northcutt concludes that the last common ancestor of all bilaterian animals, living 600–700 Mya, probably had a diffusely organized nervous system. Cephalic neural ganglia apparently evolved soon thereafter and were retained in many lineages. Truly complex brains evolved even later and did so repeatedly, in mollusks, arthropods, and chordates (including vertebrates). This conclusion contrasts sharply with the conclusions of other researchers, who are struck by similarities in developmental gene expression patterns among vertebrate, insect, and annelid nervous systems. To them, these similarities must represent homologies. That is, they argue that similar gene expression patterns must have existed in the last common ancestor of fruit flies, vertebrates, and worms. Northcutt begs to differ, arguing that the expression of these genes in brains is caused by convergent evolution, perhaps by the co-option of gene networks that predate brains. This debate will require more data for a full resolution.