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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The Caribbean reef shark infrequently attacks humans. In general, a shark attack on a human is behaviorally similar to an attack upon natural prey. A human is more susceptible to being attacked if the shark is cornered and feels that there is no escape route. In situations like these, the shark may rake the victim during the attack resulting in lacerations.
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They are also found in mangrove areas, moving in and out with the tide and even in fresh water near the sea. They occur singly or in small groups. Adults often aggregate in reef channels at low tide. This is one of the three most common reef sharks in the Indo-Pacific, the two others are the grey reef shark, Carcharhinus amblyrhynchos and whitetip reef shark, Triaenodon obesus.
There is a variety of biotic reef types, including oyster reefs and sponge reefs, but the most massive and widely distributed are tropical coral reefs. Although corals are major contributors to the framework and bulk material comprising a coral reef; the organisms most responsible for reef growth against the constant assault from ocean waves are calcareous algae, especially, although not entirely, coralline algae.