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Compensatory Evolution within Viral RNA Structure: The Potential Role of Stable Intermediates in RNA Structural Heterogeneity
Author(s) -
Magalis Brittany Rife,
Tolbert Blanton S,
Salemi Marco,
Kosakovsky Pond Sergei L
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb191
Subject(s) - rna , biology , nucleic acid structure , computational biology , genetics , population , nucleic acid secondary structure , phylogenetic tree , genome , evolutionary biology , gene , demography , sociology
Fast evolving viruses, such as human immunodeficiency virus (HIV), exist as a heterogeneous population of genotypic variants, each potentially with its own distinct RNA structural variant. Owing to the inherently compact nature of the viral genome, it is not unreasonable to believe that viruses such as HIV have adapted to take advantage of both sequence and structure heterogeneity, posing issues for RNA‐mediated drug targeting. Evolutionary analysis of compensatory mutations, using a variety of phylogenetic methods, is often used to evaluate RNA structure preservation and function. One such method is based on the identification of co‐varying sites along a single branch within the corresponding phylogeny of sequences. Despite the power of this method when applied to slower evolving organisms (e.g., vertebrate ribosomal RNA), viral genomic regions containing well‐characterized structure, such as the HIV 5’ untranslated region, consistently present very little evidence of co‐variation in the face of high sequence heterogeneity. We hypothesize that allowing for co‐variation to occur over multiple, neighboring branches would increase the robustness of this method in identifying biologically relevant RNA structures and that non‐covarying nucleotide substitutions that occur along the connecting internal branches act to stabilize structures within a population minority. We propose to integrate this approach into a Bayesian graphical network (BGN) framework for identification of larger (>2) networks of co‐evolving sites potentially acting to maintain the predominant RNA structure. Additional investigation using this method and experimental analyses are ongoing to uncover the role of the putative intermediate, minority structures in RNA structural heterogeneity, specifically within the host. Support or Funding Information Funding: NIH‐NIGMS U01 GM110749 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .