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The most basal Thamnophiine clade recovered by Zaher et al. (2019) included the Liodytes, Clonophis, Haldea, and Virginia genera. These are a mixture of fossorial, terrestrial, and semi-aquatic species. Clonophis exploits an unusual aquatic habitat – crayfish burrows; both Haldea and Virginia are small fossorial species. Liodytes contain some of the most aquatic North American snakes.
The ancestor of North American natricids immigrated from Eurasia sometime before the early Miocene (~19–18 Ma). We know this because the earliest known Western Hemisphere natricid fossils date to the early Miocene, and we know they shared an ancestor because of shared anatomy and DNA.

There are no highly specialized aquatic pythons that converge with the anacondas – the highly aquatic boas. However, some python species are best considered semi-aquatic. The largest pythons (Malayopython reticulatus, Python sebae, Python natalensis, Python bivittatus) use aquatic situations to hunt and thermoregulate. The largest pythons are habitat generalists, but they are also frequently associated with water. The large body size may be possible because of their buoyance in water, making movement more efficient.

The highly aquatic and unique file snakes have loose, baggy skin and minor, rough scales, each with sensory organs. Their short tails are round, prehensile, flat, and sword-like; the eyes and valvular nostrils are dorsally or dorsolateral. Their lack of muscle tone is spectacular and can only be fully appreciated by handling one, a physiological feature restricting them to an entirely aquatic lifestyle. The rough, file-like surface of the skin and its loose folds are used in catching and holding slippery, mucus-covered fish. Their maxillary teeth are similar in size, long, and fluted on the sides and posterior surfaces. The fluted condition is found in many fish-eating snakes.

The two species that compose the genus Farancia are considered some of the most aquatic snakes in North America, but both species are known to wander overland (Steen et al. 2013). Droughts may trigger their movement from a wetland, and excessive rainfall may also trigger their movement. Females will also move overland to nest. Both species take aquatic prey. Semlitsch et al. (1988) have described juvenile emergence in both the Fall and Spring and note that hatchlings may benefit from Fall emergence by feeding before their first winter. However, Fall emergence may present the hatchlings with dried or reduced aquatic habitats, while spring emergence would have abundant habitat and food (larval salamanders).
The members of the genus are known to have maternal attendance of eggs, a highly specific diet of elongated prey, American eels (Anguilla rostrata), and the eel-like salamanders of the genera Siren and Amphiuma.

The largest boas, the highly aquatic anacondas (Eunectes), are relatively well known. The oldest and largest member of the clade (Titanoboa) was aquatic, and today, the most aquatic members of the family are the anacondas of the genus Eunectes.

Anacondas are Neotropical snakes found east of the Andes. Four extant species and one fossil species compose the genus. The clade includes the largest snake, the Green Anaconda, Eunectes murinus, which reaches at least 8 m and has the greatest mass (in females) of any extant snake (250 kg). Eunectes is derived from a Greek word that means “good swimmer.” The aquatic habitats of these snakes are well documented. Pizzatto et al. (2007) found an aquatic habitat to be a synapomorphy for this genus. The large body size, a relatively long tail, and the dorsal positioning of the eyes and nares are all traits associated with life in water.