THE EVOLUTION OF TITIN AND RELATED GIANT MUSCLE PROTEINS

Titin and twitchin are giant proteins expressed in muscle. They are ma inly composed of domains belonging to the fibronectin class III and im munoglobulin c2 families, repeated many times. In addition, both prote ins have a protein kinase domain near the C-terminus. This paper explo res the evolution of these and related muscle proteins in an attempt t o determine the order of events that gave rise to the different repeat patterns and the order of appearance of the proteins. Despite their g reat similarity at the level of sequence organization, titin and twitc hin diverged from each other at least as early as the divergence betwe en vertebrates and nematodes. Most of the repeating units in titin and twitchin were estimated to derive from three original domains. Chicke n smooth-muscle myosin light-chain kinase (smMLCK) also has a kinase d omain, several immunoglobulin domains, and a fibronectin domain. From a comparison of the kinase domains, titin is predicted to have appeare d first during the evolution of the family, followed by twitchin and w ith the vertebrate MLCKs last to appear. The so-called C-protein from chicken is also a member of this family but has no kinase domain. Its origin remains unclear but it most probably pre-dates the titin/twitch in duplication.