A Method for the Annotation of Functional Similarities of Coding DNA Sequences: the Case of a Populated Cluster of Transmembrane Proteins.

The analysis of a large number of human and mouse genes codifying for a populated cluster of transmembrane proteins revealed that some of the genes significantly vary in their primary nucleotide sequence inter-species and also intra-species. In spite of that divergence and of the fact that all these genes share a common parental function we asked the question of whether at DNA level they have some kind of common compositional structure, not evident from the analysis of their primary nucleotide sequence. To reveal the existence of gene clusters not based on primary sequence relationships we have analyzed 13574 human and 14047 mouse genes by the composon-clustering methodology. The data presented show that most of the genes from each one of the samples are distributed in 18 clusters sharing the common compositional features between the particular human and mouse clusters. It was observed, in addition, that between particular human and mouse clusters having similar composon-profiles large variations in gene population were detected as an indication that a significant amount of orthologs between both species differs in compositional features. A gene cluster containing exclusively genes codifying for transmembrane proteins, an important fraction of which belongs to the Rhodopsin G-protein coupled receptor superfamily, was also detected. This indicates that even though some of them display low sequence similarity, all of them, in both species, participate with similar compositional features in terms of composons. We conclude that in this family of transmembrane proteins in general and in the Rhodopsin G-protein coupled receptor in particular, the composon-clustering reveals the existence of a type of common compositional structure underlying the primary nucleotide sequence closely correlated to function.