Journal of Phylogenetics & Evolutionary Biology

Evolution of Mammalian KELL Blood Group Glycoproteins and Genes (KEL): Evidence for a Marsupial Origin from an Ancestral M13 Type II Endopeptidase Gene

Abstract

Roger S Holmes

KELL is a member of the M13 family of type II neutral endopeptidases, which functions as a blood group antigen in human and animal populations. KELL amino acid sequences and structures and KEL gene locations were examined using bioinformatic data from several mammalian genome projects. Mammalian KELL sequences shared 55-99% identity, as compared with 21-31% sequence identities with other M13-like family members. Four predicted N-glycosylation sites were conserved among the mammalian KELL proteins examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied, including active site residues, predicted disulfide forming Cys residues, cytoplasmic, transmembrane and extracellular sequences and KELL C-terminus amino acid sequences. Mammalian KEL genes usually contained 18 or 19 coding exons on the direct strand. abhi binding sites within the human KEL promoter may regulate transcription within erythroid cells. Phylogenetic analyses examined the relationships and potential evolutionary origins of the mammalian KEL gene with six other vertebrate neutral endopeptidase M13 family genes. These suggested that KEL originated in an ancestral marsupial genome from a gene duplication event of a neutral endopeptidase M13-like gene.