Cdc42, a small GTPase, regulates actin polymerization and other signaling p
athways through interaction with many different downstream effector protein
s. Most of these effector proteins contain a Cdc42-binding domain, called a
CRIB domain. Here, we describe the evolutionary analysis of these CRIB-con
taining proteins in yeast, worms, flies and humans. The number of CRIB-cont
aining effector proteins increases from yeast to humans, involving both an
increase within families and the emergence of new families. These evolution
ary changes correlate with the development of the more complex signaling pa
thways present in higher organisms.