Molecular characterization of tp53 gene diversity among elephant populations in kenya

Abstract

P53 is the protein encoded by the TP53 tumor suppressor gene. P53 plays an essential role in cancer prevention. In-depth analysis of comparative genomics might hold the promise of overcoming cancer in the near future. Elephant TP53 gene has been demonstrated to prevent against various forms of cancer, mainly Osteosarcoma, prostate Cancer, and Glioblastoma. The aim of this study was to determine the genetic diversity of TP53 genes among elephant populations in Kenya and to identify any TP53 gene mutations in elephants with cancerous tumors. The study was conducted in Samburu Laikipia Ecosystem and Tsavo East National Park. Samples were collected during a different population study undertaken by the Kenya Wildlife Service from 45 elephants in different herds including one tumor sample from an elephant undergoing treatment. Ten TP53 exon regions were sequenced and compared to reference samples to check for any Single Nucleotide Polymorphisms (SNPs). The study results show that elephant TP53 gene is highly conserved with mutations observed only in one exon out of the ten. 3 haplotypes were recovered, wildtype with GG base corresponding to the reference, a heterozygous mutant with GT, and a homozygous mutant with TT at the SNP. Out of the 45 elephants sampled a total of 25 had mutations. The homozygous mutants were significantly higher in the Samburu Laikipia Ecosystem, specifically Olpejeta, indicating it could be the source population. Only 5/23 elephants showed significant variation in Olpejeta as they were homozygous mutant. The Tsavo population also showed geographic variation with only one elephant having unique homozygous variation GG →TT with 12 others having heterozygous GG→GT. These SNPs are being reported for the first time in the African elephant TP53 gene. The study also showed that this SNP mutation in TP53 gene at exon 3 manifesting as GTG→GTT transversion did not affect the amino acid translation. This goes to support the theory that elephants have a highly conserved TP53 region. This study reported that there was no genetic variability in TP53 Gene isolated in the cancer tumor from Kenyan elephant with Exon 3 in elephant diagnosed with clinical squamous cell carcinoma. In conclusion, there was geographical variation in TP53 gene of the African elephant population. Also, TP53 region is highly conserved in elephants, and this goes a long way in protecting them against cancer. There is a high chance of unreported genomic variation in other elephant population as the study focused only on 2 out of 54 national park and reserves in Kenya. Therefore, from the study its recommended to have a tumor bank of wild animals and continue further studies on the remaining copies of the elephant TP53 gene to better understand their roles. .