Background: The recent availability of sequenced genomes from a broad array of chordates (cephalochordates, urochordates and vertebrates) has allowed us to systematically analyze the evolution of uroplakins: tetraspanins (UPK1a and UPK1b families) and their respective partner proteins (UPK2 and UPK3 families).
Results: We report here: (1) the origin of uroplakins in the common ancestor of vertebrates, (2) the appearance of several residues that have statistically significantly positive dN/dS ratios in the duplicated paralogs of uroplakin genes, and (3) the existence of strong coevolutionary relationships between UPK1a/1b tetraspanins and their respective UPK2/UPK3-related partner proteins. Moreover, we report the existence of three new UPK2/3 family members we named UPK2b, 3c and 3d, which will help clarify the evolutionary relationships between fish, amphibian and mammalian uroplakins that may perform divergent functions specific to these different and physiologically distinct groups of vertebrates.
Conclusions: Since our analyses cover species of all major chordate groups this work provides an extremely clear overall picture of how the uroplakin families and their partner proteins have evolved in parallel. We also highlight several novel features of uroplakin evolution including the appearance of UPK2b and 3d in fish and UPK3c in the common ancestor of reptiles and mammals. Additional studies of these novel uroplakins should lead to new insights into uroplakin structure and function.