Viruses · 2026
Molecular Evolution of the Chikungunya Virus E1 Gene in Saudi Arabia: Predominance of Purifying Selection and ECSA/IOL Lineage Circulation.
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Farrag Mohamed A
Аннотация
BACKGROUND: Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused millions of cases worldwide, yet its molecular epidemiology in Saudi Arabia remains poorly understood. This study integrates bioinformatic analysis of the envelope gene (E1) gene sequences from Saudi isolates with global genotypes to characterize circulating lineages, selection pressures and stability effects of endemic mutations.
METHODS: A total of 109 CHIKV E1 sequences (1155 bp) representing the East/Central/South African (ECSA), Asian, and West African genotypes were retrieved from GenBank and GISAID. Phylogenetic relationships were reconstructed using maximum likelihood (IQ-TREE). Codon-based selection analyses were performed with MEME, FEL, SLAC, and FUBAR. The structural effects of nine missense mutations were assessed using DynaMut and consensus predictors (DUET, mCSM).
RESULTS: All seven Saudi isolates clustered within the ECSA-Indian Ocean Lineage (IOL) subclade with strong bootstrap support (≥95%). Short branch lengths among Saudi strains indicated recent common ancestry and limited local divergence, suggesting possible repeated introductions or limited local circulation. No codon showed robust evidence of positive selection across multiple methods. However, episodic diversifying selection was detected at codon 99 (MEME, p = 0.01), while pervasive purifying selection acted on numerous sites (e.g., codons 135, 307, 344; strong signals across FEL, SLAC, and FUBAR). A single conserved N-linked glycosylation site was present at residue 141 (NITV motif) in all Saudi and most global strains. Three mutations unique to or prominent in Saudi isolates (N20H, L136F, A249T) were identified; consensus stability predictions (DUET) classified them as destabilizing.
CONCLUSIONS: Saudi CHIKV strains belong exclusively to the ECSA-IOL lineage and exhibit strong purifying selection on the E1 gene, consistent with functional constraints on this essential fusion protein. The identified Saudi-associated mutations appear to be non-adaptive, tolerated changes. These findings underscore the value of continued genomic surveillance to monitor potential adaptive evolution, particularly in the context of mass gatherings and competent Aedes vectors.
METHODS: A total of 109 CHIKV E1 sequences (1155 bp) representing the East/Central/South African (ECSA), Asian, and West African genotypes were retrieved from GenBank and GISAID. Phylogenetic relationships were reconstructed using maximum likelihood (IQ-TREE). Codon-based selection analyses were performed with MEME, FEL, SLAC, and FUBAR. The structural effects of nine missense mutations were assessed using DynaMut and consensus predictors (DUET, mCSM).
RESULTS: All seven Saudi isolates clustered within the ECSA-Indian Ocean Lineage (IOL) subclade with strong bootstrap support (≥95%). Short branch lengths among Saudi strains indicated recent common ancestry and limited local divergence, suggesting possible repeated introductions or limited local circulation. No codon showed robust evidence of positive selection across multiple methods. However, episodic diversifying selection was detected at codon 99 (MEME, p = 0.01), while pervasive purifying selection acted on numerous sites (e.g., codons 135, 307, 344; strong signals across FEL, SLAC, and FUBAR). A single conserved N-linked glycosylation site was present at residue 141 (NITV motif) in all Saudi and most global strains. Three mutations unique to or prominent in Saudi isolates (N20H, L136F, A249T) were identified; consensus stability predictions (DUET) classified them as destabilizing.
CONCLUSIONS: Saudi CHIKV strains belong exclusively to the ECSA-IOL lineage and exhibit strong purifying selection on the E1 gene, consistent with functional constraints on this essential fusion protein. The identified Saudi-associated mutations appear to be non-adaptive, tolerated changes. These findings underscore the value of continued genomic surveillance to monitor potential adaptive evolution, particularly in the context of mass gatherings and competent Aedes vectors.