The DUP gene family of Saccharomyces cerevisiae comprises 23 members that can be divided into two subfamilies--DUP240 and DUP380. The location of the DUP loci suggests that at least three mechanisms were responsible for their genomic dispersion: nonreciprocal translocation at chromosomal ends, tandem duplication and Ty-associated duplication. The data we present here suggest that these nonessential genes encode proteins that facilitate membrane trafficking processes. Dup240 proteins have three conserved domains (C1, C2 and C3) and two predicted transmembrane segments (H1 and H2). A direct repetition of the C1-H1-H2-C2 module is observed in Dup380p sequences. In this article, we propose an evolutionary model to account for the emergence of the two gene subfamilies.