Duplication and Positive Selection drove Uggt-2 neofunctionalization in Caenorhabditis

MIRANDA, S.; CASTRO, O.A.; ACOSTA, G.; ACOSTA, G.; ROSSI, M.S.; CARABALLO, D. A.; ROSSI, M.S.; CARABALLO, D. A.; MIRANDA, S.; CASTRO, O.A.

Buenos Aires

Congreso; Reunion conjunta de sociedades de biociencias 2017; 2017

SAIB/SAIC

UGGT (UDP-Glc::glycoprotein glucosyltransferase) discriminate folded from misfolded glycoproteins, is the key component of the quality control mechanism of glycoprotein folding that ensures that only properly folded proteins exit the ER. In vertebrates and in the nematode genus Caenorhabditis there are two homologous genes encoding UGGT-like proteins. Expression of both Caenorhabditis genes in S. pombe mutants devoid of UGGT activity showed that UGGT-1 is active while UGGT-2 although being an essential protein in worms apparently does not display a canonical UGGT activity. The aim of this study was to explore the origin and evolution of both Caenorhabditis UGGTs. Bayesian phylogenetic analyses were carried out in 189 UGGT sequences representing all major eukaryotic groups. The Caenorhabditis and the vertebrate clades are reciprocally monophyletic, and both split into two identical subtrees, revealing that UGGT went through independent duplications in these two lineages. Conservation and selection analyses were performed within the Caenorhabditis clade applying codon-based and lineage-based approaches analyzing the two protein domains separately, reflecting a generalized background of purifying selection in both UGGTs, suggesting that the two gene copies have been subjected to functional constrains. The catalytic domain is highly conserved as a consequence of a strong negative selective pressure, and shows almost no evidences of positive selection. In contrast, the recognition domain has undergone a positive diversifying selection process, wich showed evidences of Episodic Diversifying Selection in UGGT 2. A probable outcome of the observed selective scenario is that UGGT 1 retained the canonical function, while UGGT 2 may have retained only the catalytic domain and consequently may recognize a different substrate. In this sense, UGGT 2 would have experienced a neofunctionalization driven by diversifying (positive) selection.