Based on morphological similarities, Jack Garrick in 1982 grouped this species with the bignose shark (C. altimus) and the sandbar shark (C. plumbeus), while Leonard Compagno in 1988 placed it as the sister species of the grey reef shark (C. amblyrhynchos). A phylogenetic analysis based on allozyme data, published by Gavin Naylor in 1992, indicated that the Caribbean reef shark is the sister taxon to a clade formed by the Galapagos shark (C. galapagensis), dusky shark (C. obscurus), oceanic whitetip shark (C. longimanus), and the blue shark (Prionace glauca). However, more work is required to fully resolve the interrelationships within Carcharhinus.
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On the infrequent occasions when they swim in oceanic waters, grey reef sharks often associate with marine mammals or large pelagic fishes, such as sailfish (Istiophorus platypterus). There is an account of around 25 grey reef sharks following a large pod of bottlenose dolphins (Tursiops sp.), along with 25 silky sharks (C. falciformis) and a single silvertip shark. Rainbow runners (Elagatis bipinnulata) have been observed rubbing against grey reef sharks, using the sharks' rough skin to scrape off parasites.
The Caribbean reef shark feeds on a wide variety of reef-dwelling bony fishes and cephalopods, as well as some elasmobranchs such as eagle rays (Aetobatus narinari) and yellow stingrays (Urobatis jamaicensis). It is attracted to low-frequency sounds, which are indicative of struggling fish. In one observation of a 2 m (6.6 ft) long male Caribbean reef shark hunting a yellowtail snapper (Lutjanus crysurus), the shark languidly circled and made several seemingly "half-hearted" turns towards its prey, before suddenly accelerating and swinging its head sideways to capture the snapper at the corner of its jaws. Young sharks feed on small fishes, shrimps, and crabs. Caribbean reef sharks are capable of everting their stomachs, which likely serves to cleanse indigestible particles, parasites, and mucus from the stomach lining.
Juvenile Caribbean reef sharks are preyed upon by larger sharks such as the tiger shark (Galeocerdo cuvier) and the bull shark (C. leucas). Few parasites are known for this species; one is a dark variegated leech often seen trailing from its first dorsal fin. Off northern Brazil, juveniles seek out cleaning stations occupied by yellownose gobies (Elacatinus randalli), which clean the sharks of parasites while they lie still on the bottom. Horse-eye jacks (Caranx latus) and bar jacks (Carangoides ruber) routinely school around Caribbean reef sharks.
A reef is a bar of rock, sand, coral or similar material, lying beneath the surface of water. Many reefs result from abiotic processes (i.e. deposition of sand, wave erosion planing down rock outcrops, and other natural processes), but the best known reefs are the coral reefs of tropical waters developed through biotic processes dominated by corals and coralline algae.