title: Sequence and structural aspects of functional diversification in class I alpha-mannosidase evolution.
abstract: BACKGROUND
  Class I alpha-mannosidases comprise a homologous and functionally diverse family of glycoside hydrolases. Phylogenetic analysis based on an amino acid sequence alignment of the catalytic domain of class I alpha-mannosidases reveals four well-supported phylogenetic groups within this family. These groups include a number of paralogous members generated by gene duplications that occurred as far back as the initial divergence of the crown-group of eukaryotes. Three of the four phylogenetic groups consist of enzymes that have group-specific biochemical specificity and/or sites of activity. An attempt has been made to uncover the role that natural selection played in the sequence and structural divergence between the phylogenetically and functionally distinct Endoplasmic Reticulum (ER) and Golgi apparatus groups.
  
  
  RESULTS
  Comparison of site-specific amino acid variability profiles for the ER and Golgi groups revealed statistically significant evidence for functional diversification at the sequence level and indicated a number of residues that are most likely to have played a role in the functional divergence between the two groups. The majority of these sites appear to contain residues that have been fixed within one organelle-specific group by positive selection. Somewhat surprisingly these selected residues map to the periphery of the alpha-mannosidase catalytic domain tertiary structure. Changes in these peripherally located residues would not seem to have a gross effect on protein function. Thus diversifying selection between the two groups may have acted in a gradual manner consistent with the Darwinian model of natural selection.
  
  
  BACKGROUND
  bishogr@millsaps.edu.
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
authors.forename: I K
authors.initials: IK
authors.lastname: Jordan
authors.forename: G R
authors.initials: GR
authors.lastname: Bishop
authors.forename: D S
authors.initials: DS
authors.lastname: Gonzalez
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D004721:Endoplasmic Reticulum / Q000201:enzymology; D019143:Evolution, Molecular; D020440:Gene Duplication; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008361:Mannosidases / Q000737:chemistry* / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity; D043323:alpha-Mannosidase
chemical_list: D008361:Mannosidases; D043323:alpha-Mannosidase