Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns.

Irene Hoxie,John J Dennehy

doi:10.3390/v13081460

Irene Hoxie, John J Dennehy

Open Access

https://doi.org/10.3390/v13081460

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Abstract

Reassortment of the Rotavirus A (RVA) 11-segment dsRNA genome may generate new genome constellations that allow RVA to expand its host range or evade immune responses. Reassortment may also produce phylogenetic incongruities and weakly linked evolutionary histories across the 11 segments, obscuring reassortment-specific epistasis and changes in substitution rates. To determine the co-segregation patterns of RVA segments, we generated time-scaled phylogenetic trees for each of the 11 segments of 789 complete RVA genomes isolated from mammalian hosts and compared the segments’ geodesic distances. We found that segments 4 (VP4) and 9 (VP7) occupied significantly different tree spaces from each other and from the rest of the genome. By contrast, segments 10 and 11 (NSP4 and NSP5/6) occupied nearly indistinguishable tree spaces, suggesting strong co-segregation. Host-species barriers appeared to vary by segment, with segment 9 (VP7) presenting the weakest association with host species. Bayesian Skyride plots were generated for each segment to compare relative genetic diversity among segments over time. All segments showed a dramatic decrease in diversity around 2007 coinciding with the introduction of RVA vaccines. To assess selection pressures, codon adaptation indices and relative codon deoptimization indices were calculated with respect to different host genomes. Codon usage varied by segment with segment 11 (NSP5) exhibiting significantly higher adaptation to host genomes. Furthermore, RVA codon usage patterns appeared optimized for expression in humans and birds relative to the other hosts examined, suggesting that translational efficiency is not a barrier in RVA zoonosis.

Highlights

The high mutation rates and large population sizes of RNA viruses allow them to rapidly explore adaptive landscapes, expand host-ranges, and adapt to new environments.Segmented RNA viruses may undergo ‘reassortment’ whereby viruses swap entire genome segments during coinfection [1]
We show that Rotavirus A (RVA)’s segments have distinct evolutionary histories, demonstrating the impact reassortment has had on mammalian RVA between the late 1950s to 2017
Multi-dimensional scaling of the random, post-burn-in sampling of BEAST trees for each of the 11 segments revealed that segments 4 and 9 occupy distinct tree spaces from each other and the rest of the genome (Figure 2)

Summary

Introduction

The high mutation rates and large population sizes of RNA viruses allow them to rapidly explore adaptive landscapes, expand host-ranges, and adapt to new environments. Segmented RNA viruses may undergo ‘reassortment’ whereby viruses swap entire genome segments during coinfection [1]. Reassortment may allow rapid evolution of specific viral traits such as, for example, the acquisition of novel spike glycoproteins during the emergence of H1N1 influenza A in 2009 [2]. Reassortment among segmented dsRNA rotaviruses may have significant implications for human health [3], but it is challenging to determine the prevalence of rotavirus reassortment in nature. Our motivation here is to elucidate apparent restrictions (or lack thereof) to RVA genetic exchange in nature by comparing the relative linkage between each of the RVA segments as shown by phylogeny. We parse the evolutionary constraints that may contribute to the distinct phylogenies of each segment

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