THE IMPACT OF ENDOGENOUS RETROVIRUS S2220 ON MULE DEER ISY1 GENE EXPRESSION

Open Access
Author:
Bogale, Kaleb Tadesse
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Dr. Mary Poss, Thesis Supervisor
  • Dr. Bernhard Lüscher, Honors Advisor
Keywords:
  • Endogenous retrovirus
  • ERV
  • LTR
  • long terminal repeat
  • solo LTR
  • solo long terminal repeat
  • gene expression
  • mule deer
  • Odocoileus hemionus
  • RNA
  • Splicing
  • retrovirus
  • pre-mrna splicing gene
  • ISY1 gene
  • isy1
  • gene regulation
  • hardy-weinberg equilibrium
  • population genetics
  • Bos taurus
  • domestic cow
  • Ovis aris
  • sheep
Abstract:
Endogenous retroviruses (ERVs) are retroviruses that infect germline cells and become permanent fixtures at a specific site in the host genome. In a continually evolving ERV-host relationship, ERVs may maintain the ability to completely restructure nearby host gene expression with their long terminal repeat (LTR). I am studying how an insertional polymorphic cervid ERV (CrERV), S2220, in Odocoileus hemionus (mule deer) impacts the nearby host pre-mRNA splicing ISY1 gene expression. I hypothesized CrERV S2220 restructured the ISY1 gene regulatory network and altered the transcript profile by acting as an alternative, bidirectional promoter of the ISY1 gene and CrERV S2220. First, the prevalence and genotype of CrERV S2220 in 28 mule deer from Montana and Wyoming was investigated. We found CrERV S2220 was fixed and the most abundant state, comprising 25/28 total mule deer samples, in both Montana and Wyoming mule deer populations. Second, the host genome flanking the CrERV S2220 integration site was compared between mule deer from Montana or Wyoming and mule deer with or without CrERV S2220. The host genome near the integration site was conserved in mule deer. Third, the predicted mule deer ISY1 gene model was generated through a comparative genomic analysis with close relatives, Bos taurus (domestic cow) and Ovis aris (sheep). Since no cervid genomes are available, we were the first to compare the gene structure of the cervid ISY1 gene (or any other cervid gene) and found the gene model is highly conserved in cervid genomes. Fourth, a qualitative transcript profile for the mule deer ISY1 gene was reported. Notably, we found the CrERV S2220 LTR is an alternative, bidirectional promoter of the ISY1 gene, as hypothesized. Two splicing variants in the mule deer ISY1 gene were found that initiated from the CrERV S2220 LTR. Future studies will identify if the CrERV S2220 LTR initiates a novel ISY1 gene transcript not found in the pre-integration site.