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Chikungunya virus 3' untranslated region: adaptation to mosquitoes and a population bottleneck as major evolutionary forces.

Chen R, Wang E, Tsetsarkin KA, Weaver SC - PLoS Pathog. (2013)

Bottom Line: Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3'UTR was due to their beneficial effects on adaptation to vectors or hosts.Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia.Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there.

View Article: PubMed Central - PubMed

Affiliation: Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

ABSTRACT
The 3' untranslated genome region (UTR) of arthropod-borne viruses is characterized by enriched direct repeats (DRs) and stem-loop structures. Despite many years of theoretical and experimental study, on-going positive selection on the 3'UTR had never been observed in 'real-time,' and the role of the arbovirus 3'UTR remains poorly understood. We observed a lineage-specific 3'UTR sequence pattern in all available Asian lineage of the mosquito-borne alphavirus, chikungunya virus (CHIKV) (1958-2009), including complicated mutation and duplication patterns of the long DRs. Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3'UTR was due to their beneficial effects on adaptation to vectors or hosts. Using reverse genetic methods, we examined the functional importance of each direct repeat. Our results suggest that adaptation to mosquitoes, rather than to mammalian hosts, is a major evolutionary force on the CHIKV 3'UTR. Surprisingly, the Asian 3'UTR appeared to be inferior to its predicted ancestral sequence for replication in both mammals and mosquitoes, suggesting that its fixation in Asia was not a result of directional selection. Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia. We propose that this introduction of a 3'UTR with deletions led to genetic drift and compensatory mutations associated with the loss of structural/functional constraints, followed by two independent beneficial duplications and fixation due to positive selection. Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there.

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Evolution history and lineage-specific structures of the CHIKV 3′UTR.On the left is the MCC (Maximum Clade Credibility) tree based on the complete ORF sequences, with the branches in each lineage collapsed. The estimated year of the most recent common ancestor (MRCA: mean and the 95% HPD values) of each clade is labeled left to the node. The 3′UTR structures, based on sequence alignment, are shown next to each lineage. Direct repeats are illustrated by different colored blocks, each of the four colors represents a different homologous sequence region. Sequence gaps in the alignment are indicated by white blocks. In the Asian lineage, two distinct derived differences are observed: 1) duplication of DR3, and duplication the of DR(1+2) region. The detailed alignment can be found in Fig. S2.
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ppat-1003591-g001: Evolution history and lineage-specific structures of the CHIKV 3′UTR.On the left is the MCC (Maximum Clade Credibility) tree based on the complete ORF sequences, with the branches in each lineage collapsed. The estimated year of the most recent common ancestor (MRCA: mean and the 95% HPD values) of each clade is labeled left to the node. The 3′UTR structures, based on sequence alignment, are shown next to each lineage. Direct repeats are illustrated by different colored blocks, each of the four colors represents a different homologous sequence region. Sequence gaps in the alignment are indicated by white blocks. In the Asian lineage, two distinct derived differences are observed: 1) duplication of DR3, and duplication the of DR(1+2) region. The detailed alignment can be found in Fig. S2.

Mentions: Despite these advances in understanding the functional roles of arboviral 3′UTRs, there is no solid evidence to relate the occurrence of indels, which appear to occur frequently during their evolution, with any particular adaptation to a given host or vector. The extensive within-species diversity in the 3′UTR of the alphavirus chikungunya virus (CHIKV), especially lineage-specific DR patterns (revealed in this study; Fig. 1), is unique within this genus of mainly mosquito-borne viruses. Together with prior reconstructions of CHIKV evolutionary history [28], as well as the relative sequence conservation and comparability among lineages, this diversity in 3′UTR sequences provides a unique opportunity for understanding their evolution and functional importance.


Chikungunya virus 3' untranslated region: adaptation to mosquitoes and a population bottleneck as major evolutionary forces.

Chen R, Wang E, Tsetsarkin KA, Weaver SC - PLoS Pathog. (2013)

Evolution history and lineage-specific structures of the CHIKV 3′UTR.On the left is the MCC (Maximum Clade Credibility) tree based on the complete ORF sequences, with the branches in each lineage collapsed. The estimated year of the most recent common ancestor (MRCA: mean and the 95% HPD values) of each clade is labeled left to the node. The 3′UTR structures, based on sequence alignment, are shown next to each lineage. Direct repeats are illustrated by different colored blocks, each of the four colors represents a different homologous sequence region. Sequence gaps in the alignment are indicated by white blocks. In the Asian lineage, two distinct derived differences are observed: 1) duplication of DR3, and duplication the of DR(1+2) region. The detailed alignment can be found in Fig. S2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3757053&req=5

ppat-1003591-g001: Evolution history and lineage-specific structures of the CHIKV 3′UTR.On the left is the MCC (Maximum Clade Credibility) tree based on the complete ORF sequences, with the branches in each lineage collapsed. The estimated year of the most recent common ancestor (MRCA: mean and the 95% HPD values) of each clade is labeled left to the node. The 3′UTR structures, based on sequence alignment, are shown next to each lineage. Direct repeats are illustrated by different colored blocks, each of the four colors represents a different homologous sequence region. Sequence gaps in the alignment are indicated by white blocks. In the Asian lineage, two distinct derived differences are observed: 1) duplication of DR3, and duplication the of DR(1+2) region. The detailed alignment can be found in Fig. S2.
Mentions: Despite these advances in understanding the functional roles of arboviral 3′UTRs, there is no solid evidence to relate the occurrence of indels, which appear to occur frequently during their evolution, with any particular adaptation to a given host or vector. The extensive within-species diversity in the 3′UTR of the alphavirus chikungunya virus (CHIKV), especially lineage-specific DR patterns (revealed in this study; Fig. 1), is unique within this genus of mainly mosquito-borne viruses. Together with prior reconstructions of CHIKV evolutionary history [28], as well as the relative sequence conservation and comparability among lineages, this diversity in 3′UTR sequences provides a unique opportunity for understanding their evolution and functional importance.

Bottom Line: Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3'UTR was due to their beneficial effects on adaptation to vectors or hosts.Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia.Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there.

View Article: PubMed Central - PubMed

Affiliation: Center for Tropical Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas, United States of America.

ABSTRACT
The 3' untranslated genome region (UTR) of arthropod-borne viruses is characterized by enriched direct repeats (DRs) and stem-loop structures. Despite many years of theoretical and experimental study, on-going positive selection on the 3'UTR had never been observed in 'real-time,' and the role of the arbovirus 3'UTR remains poorly understood. We observed a lineage-specific 3'UTR sequence pattern in all available Asian lineage of the mosquito-borne alphavirus, chikungunya virus (CHIKV) (1958-2009), including complicated mutation and duplication patterns of the long DRs. Given that a longer genome is usually associated with less efficient replication, we hypothesized that the fixation of these genetic changes in the Asian lineage 3'UTR was due to their beneficial effects on adaptation to vectors or hosts. Using reverse genetic methods, we examined the functional importance of each direct repeat. Our results suggest that adaptation to mosquitoes, rather than to mammalian hosts, is a major evolutionary force on the CHIKV 3'UTR. Surprisingly, the Asian 3'UTR appeared to be inferior to its predicted ancestral sequence for replication in both mammals and mosquitoes, suggesting that its fixation in Asia was not a result of directional selection. Rather, it may have resulted from a population bottleneck during its introduction from Africa to Asia. We propose that this introduction of a 3'UTR with deletions led to genetic drift and compensatory mutations associated with the loss of structural/functional constraints, followed by two independent beneficial duplications and fixation due to positive selection. Our results provide further evidence that the limited epidemic potential of the Asian CHIKV strains resulted from founder effects that reduced its fitness for efficient transmission by mosquitoes there.

Show MeSH
Related in: MedlinePlus