Rotavirus A Genome Segments Show Distinct Segregation and Codon Usage Patterns

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.

Genomic epidemiology of the rotavirus G2P[4] strains in coastal Kenya pre- and post-rotavirus vaccine introduction, 2012–8

“…In addition, only G2 lineage IVa-3 and P[4] lineage IVa were in circulation post-vaccine introduction suggesting reduced diversity. This is consistent with the findings of a global study ( Hoxie and Dennehy 2021 ) where vaccine introduction coincided with a sharp decline in the genetic diversity of globally circulating RVA strains despite the different timescales of the two studies.…”

Mammalian orthoreoviruses exhibit rare genotype variability in genome constellations

“…However, the availability of growing numbers of viral genome sequences has permitted more complete nucleic acid characterization, prediction of encoded proteins, and new opportunities to understand the makeup of viral genomes and to classify viruses based on genetic relatedness. For segmented viruses, sequencing and segment classification have revealed the constellations, or specific assortments, of segments that comprise viral genomes and permitted detection of reassortants, viruses that contain mixtures of segments derived from multiple parent viruses ( Anbalagan et al, 2014a ; De Grazia et al, 2016 ; Hoxie and Dennehy, 2021 ; Matthijnssens et al, 2008a ; Steel and Lowen, 2014 ; Stott et al, 1987 ; Trifkovic et al, 2021 ). Reassortment is a key driver of segmented virus evolution but appears to be limited in natural settings and is constrained by viral RNA and protein incompatibilities ( Klempa, 2018 ; Lowen, 2017 ; McDonald et al, 2016 ; Varsani et al, 2018 ; Wille and Holmes, 2020 ).…”

Genetic Profile of Rotavirus Type A in Children under 5 Years Old in Africa: A Systematic Review of Prevalence

“…The high prevalence of mixed infections observed in this study as well as other studies in the continent [ 57 ] constitutes an optimal moment for the reassortment of the rotavirus genome that can lead to the generation of new rotavirus strains and may generate new genome constellations that allow rotavirus type A to expand its host range or evade immune responses [ 97 ]. The diversity of rotavirus strains in the continent, that carry a higher burden of rotavirus mortality, could represent a challenge to the efficacy of current vaccines.…”