Phylogeny and evolution of the major intrinsic protein family

Background information. MIPs (major intrinsic proteins) form channels across biological membranes that control recruitment of water and small solutes such as glycerol and urea in all living organisms. Because of their widespread occurrence and large number, MIPs are a sound model system to understand evolutionary mechanisms underlying the generation of protein structural and functional diversity. With the recent increase in genomic projects, there is a considerable increase in the quantity and taxonomic range of MIPs in molecular databases. Results. In the present study, I compiled more than 450 non-redundant amino acid sequences of MIPs from NCBI databases. Phylogenetic analyses using Bayesian inference reconstructed a statistically robust tree that allowed the classification of members of the family into two main evolutionary groups, the GLPs (glycerol- uptake facilitators or aquaglyceroporins) and the water transport channels or AQPs (aquaporins). Separate phylogenetic analyses of each of the MIP subfamilies were performed to determine the main groups of orthology. In addition, comparative sequence analyses were conducted to identify conserved signatures in the MIP molecule. Conclusions. The earliest and major gene duplication event in the history of the MIP family led to its main functional split into GLPs and AQPs. GLPs show typically one single copy in microbes (eubacteria, archaea and fungi), up to four paralogues in vertebrates and they are absent from plants. AQPs are usually single in microbes and show their greatest numbers and diversity in angiosperms and vertebrates. Functional recruitment of NOD26-like intrinsic proteins to glycerol transport due to the absence of GLPs in plants was highly supported. Acquisition of other MIP functions such as permeability to ammonia, arsenite or CO2 is restricted to particular MIP paralogues. Up to eight fairly conserved boxes were inferred in the primary sequence of the MIP molecule. All of them mapped on to one side of the channel except the conserved glycine residues from helices 2 and 5 that were found in the opposite side.