A 2007 paper that described a series of studies by a team led by Seiji Negoro of the University of Hyogo, Japan, suggested shown that just two amino acid alterations, i.e. G181D (from Gly181 (EII′-original enzyme ) to Asp (6-aminohexanoate-dimer hydrolase (EII) )) and H266N (from His266 (EII′)to Asn (EII)), confer the Ald-hydrolytic activity to the level of the parental EII enzyme10 .[6] These results suggest that the EII has evolved by gene duplication followed by base substitution from its ancestral gene. Many other genes have been discovered which did evolve by gene duplication followed by a frameshift mutation affecting at least part of the gene.[citation needed]