Evolution and functional divergence of the anoctamin family of membrane proteins.
BACKGROUND
The anoctamin family of transmembrane proteins are found in all eukaryotes and consists of 10 members in vertebrates. Ano1 and ano2 were observed to have Ca2+ activated Cl- channel activity. Recent findings however have revealed that ano6, and ano7 can also produce chloride currents, although with different properties. In contrast, ano9 and ano10 suppress baseline Cl- conductance when co-expressed with ano1 thus suggesting that different anoctamins can interfere with each other. In order to elucidate intrinsic functional diversity, and underlying evolutionary mechanism among anoctamins, we performed comprehensive bioinformatics analysis of anoctamin gene family.


RESULTS
Our results show that anoctamin protein paralogs evolved from several gene duplication events followed by functional divergence of vertebrate anoctamins. Most of the amino acid replacements responsible for the functional divergence were fixed by adaptive evolution and this seem to be a common pattern in anoctamin gene family evolution. Strong purifying selection and the loss of many gene duplication products indicate rigid structure-function relationships among anoctamins.


CONCLUSIONS
Our study suggests that anoctamins have evolved by series of duplication events, and that they are constrained by purifying selection. In addition we identified a number of protein domains, and amino acid residues which contribute to predicted functional divergence. Hopefully, this work will facilitate future functional characterization of the anoctamin membrane protein family.
Experimental Ophthalmology, Regensburg University Medical Center, Regensburg, Germany. milenkovic@eye-regensburg.de
Vladimir M
VM
Milenkovic
Marisa
M
Brockmann
Heidi
H
Stöhr
Bernhard Hf
BH
Weber
Olaf
O
Strauss
D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels / Q000235:genetics; D019295:Computational Biology; D019143:Evolution, Molecular; D016013:Likelihood Functions; D008565:Membrane Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics; D010802:Phylogeny
C476213:ANO1 protein, human; C547813:ANO5 protein, human; C498181:ANO7 protein, human; C502609:ANO8 protein, human; D000075369:Anoctamin-1; D000075368:Anoctamins; D018118:Chloride Channels; D008565:Membrane Proteins; D009363:Neoplasm Proteins