Poster #66 - Annie Tran

Unraveling the Intricacies of HIV-1 Evolution through a Novel Near-Neutral UnBalanced Selection Theory Approach

Annie Tran, MS, Pharmaceutical Science (tranan85@rowan.edu), Department of Chemistry and Biochemistry & Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA Nicholas Paradis, PhD, Pharmaceutical Science, (paradi84@rowan.edu), Department of Chemistry and Biochemistry & Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA Xiaruiyan Xu MS, Pharmaceutical Science ( xuxiar32@rowan.edu) Department of Chemistry and Biochemistry & Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA Chun Wu, Associate Professor, (wuc@rowan.edu), Department of Chemistry and Biochemistry & Department of Biological & Biomedical Sciences, Rowan University, Glassboro, NJ 08028, USA

Human immunodeficiency virus type 1 (HIV-1) is a single-stranded RNA retrovirus. Vaccine approval for HIV-1 is challenging due to the high mutation rate that allows the virus to evade and adapt to the immune system and antivirals. Using genomic analysis and novel molecular evolution mathematical framework can help enhance the understanding (HIV-1) evolution and facilitate antiviral and vaccine development. In this study, the development of our novel substitution mutation rate ratio (c/µ) framework, where µ is approximated and independent of genetic codon tables and Markovian mutation Models, is used in the HIV-1 genome empirical sequence data to explain the mechanism of genetic variation impacting the molecular evolution of HIV-1. The (c/µ) of each of the nucleotide/amino acid sites can be calculated to infer the overall site specific selection fitness within the segments. Our results for c/µ analysis for the time and position based method found that each segment does not exhibit a molecular clock but also exhibits a L-shape c/µ distribution fitness effects, which does not follow any conventional theories of molecular evolution. We proposed our novel Near Neutral Unbalanced selection theory (NNUST), suggesting the unbalanced selection of the nearly neutral mutations and lack of molecular clock, is a hybrid theory combining ST, KNT and Ohta Nearly-Neutral Theory (ONNT) to explain the true molecular evolution of HIV-1. Furthermore, the top adaptive mutations based c/µ>1 was assembled and consistent with the literature reported adaptive and deleterious mutation effects. These novel findings provide insight and in depth investigation of the viral evolution of HIV-1.