Genetic Study of NK-Lysin in Cattle

Human granulysin and pig NK-Lysin are novel antimicrobial and tumorlytic peptides present in the granules of cytotoxic T lymphocytes and natural killer cells. They belong to the SAPLIP (Saposin-like protein) family, which share a conserved three-dimensional structure. Granulysin is an effector protein in immune system that is active against bacteria, fungi, protozoa, viruses and cancer cells. While well-studied in human and pig, NK-Lysin homologues have been identified in several other animals, including the chicken, horse, sheep, water buffalo, cattle and catfish, but have received much less attention.

My study focused on the genomic structure and organization of bovine NK-Lysin genes. Trace file sequences analysis from the genome sequence reference animal suggested that there are at least four NK-Lysin genes in the bovine genome. On the other hand, analysis of sequence from UMD3.1 assembly between two flanking genes, ATOH8 and SFTPB, suggested duplications of two pieces of a fragment (~13Kb) which includes the NK-Lysin region. To avoid the complexity of allelic variation, we studied the NK-Lysin in BAC clones, and the data demonstrated that multiple NK-Lysin genes with extensive variable nucleotide variations rather than a single copy exist in the bovine genome. We found synonymous SNPs and also non-synonymous SNPs that may affect NK-Lysin peptide activity. Antimicrobial activity is being compared in peptides derived from different genomic sequences.