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Genomic diversity and evolution of the lyssaviruses.

Delmas O, Holmes EC, Talbi C, Larrous F, Dacheux L, Bouchier C, Bourhy H - PLoS ONE (2008)

Bottom Line: To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution.In doing so we significantly increase the extent of genome sequence data available for these important viruses.A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur, UPRE Lyssavirus Dynamics and Host Adaptation, World Health Organization Collaborating Centre for Reference and Research on Rabies, Paris, France.

ABSTRACT
Lyssaviruses are RNA viruses with single-strand, negative-sense genomes responsible for rabies-like diseases in mammals. To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution. Herein, we report the first genomic and evolutionary analysis using complete genome sequences of all recognised lyssavirus genotypes, including 14 new complete genomes of field isolates from 6 genotypes and one genotype that is completely sequenced for the first time. In doing so we significantly increase the extent of genome sequence data available for these important viruses. Our analysis of these genome sequence data reveals that all lyssaviruses have the same genomic organization. A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats. We also suggest that multiple genotypes may exist within the diversity of viruses currently classified as 'Lagos Bat'. In sum, we show that rigorous phylogenetic techniques based on full length genome sequence provide the best discriminatory power for genotype classification within the lyssaviruses.

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Schematic representation of lyssavirus genome organization and sequence similarity among 24 aligned genomes.A. The 3′ leader, N-, P-, M-, G- and L-coding regions and the 5′ trailer region are shown. B. Sequence similarity is calculated by moving a window of 60 nucleotides along the aligned sequences. C. Sequence similarity is calculated by moving a window of 20 amino acids along the aligned sequences. Within each window, the similarity of any one position is taken to be the average of all the possible pairwise scores at that position and is calculated using PLOTCON (available at http://bioweb.pasteur.fr/seqanal/interfaces/plotcon.html).
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pone-0002057-g001: Schematic representation of lyssavirus genome organization and sequence similarity among 24 aligned genomes.A. The 3′ leader, N-, P-, M-, G- and L-coding regions and the 5′ trailer region are shown. B. Sequence similarity is calculated by moving a window of 60 nucleotides along the aligned sequences. C. Sequence similarity is calculated by moving a window of 20 amino acids along the aligned sequences. Within each window, the similarity of any one position is taken to be the average of all the possible pairwise scores at that position and is calculated using PLOTCON (available at http://bioweb.pasteur.fr/seqanal/interfaces/plotcon.html).

Mentions: All genomes have the same structural organization although their lengths varied between 11918 nt. (GT7) and 12016 nt. (GT2) (Table 2). The predicted size of the coding regions is similar among genotypes, with the M protein identical in length across all genotypes and the P protein the most variable [14], [21], 22. As observed in other RNA viruses, all genotypes show a bias toward G+C richness [23], with the lowest G+C content observed in GT2 and the highest in GT1 (Table 2). All genomes have a polycistronic genome organization surrounded by untranslated regions (Table S2) similar to that already described [10], [14]. The extent of genetic diversity, reflected in percentage identity, varies within and among proteins (Figure 1), in the order N>L>M>G>P (95.2, 94.2, 92.3, 85.8, 81.5% amino acid identity, respectively). A similar pattern was previously observed using more limited data sets [14]. This same order was also observed in terms of overall selection pressure, measured as the mean ratio of nonsynonymous (dN) to synonymous substitutions (dS) per site (dN/dS), estimated using the maximum likelihood SLAC (Single Likelihood Ancestor Counting; http://www.datamonkey.org/) method [24]: N = 0.048; L = 0.055; M = 0.078; G = 0.119; P = 0.187. This approximately four-fold difference in mean dN/dS reflects major differences in selective constraint among proteins. This trend was also reflected in previous analyses of full length genomes of vaccine strains [22] and through partial gene comparisons [25], [26].


Genomic diversity and evolution of the lyssaviruses.

Delmas O, Holmes EC, Talbi C, Larrous F, Dacheux L, Bouchier C, Bourhy H - PLoS ONE (2008)

Schematic representation of lyssavirus genome organization and sequence similarity among 24 aligned genomes.A. The 3′ leader, N-, P-, M-, G- and L-coding regions and the 5′ trailer region are shown. B. Sequence similarity is calculated by moving a window of 60 nucleotides along the aligned sequences. C. Sequence similarity is calculated by moving a window of 20 amino acids along the aligned sequences. Within each window, the similarity of any one position is taken to be the average of all the possible pairwise scores at that position and is calculated using PLOTCON (available at http://bioweb.pasteur.fr/seqanal/interfaces/plotcon.html).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2327259&req=5

pone-0002057-g001: Schematic representation of lyssavirus genome organization and sequence similarity among 24 aligned genomes.A. The 3′ leader, N-, P-, M-, G- and L-coding regions and the 5′ trailer region are shown. B. Sequence similarity is calculated by moving a window of 60 nucleotides along the aligned sequences. C. Sequence similarity is calculated by moving a window of 20 amino acids along the aligned sequences. Within each window, the similarity of any one position is taken to be the average of all the possible pairwise scores at that position and is calculated using PLOTCON (available at http://bioweb.pasteur.fr/seqanal/interfaces/plotcon.html).
Mentions: All genomes have the same structural organization although their lengths varied between 11918 nt. (GT7) and 12016 nt. (GT2) (Table 2). The predicted size of the coding regions is similar among genotypes, with the M protein identical in length across all genotypes and the P protein the most variable [14], [21], 22. As observed in other RNA viruses, all genotypes show a bias toward G+C richness [23], with the lowest G+C content observed in GT2 and the highest in GT1 (Table 2). All genomes have a polycistronic genome organization surrounded by untranslated regions (Table S2) similar to that already described [10], [14]. The extent of genetic diversity, reflected in percentage identity, varies within and among proteins (Figure 1), in the order N>L>M>G>P (95.2, 94.2, 92.3, 85.8, 81.5% amino acid identity, respectively). A similar pattern was previously observed using more limited data sets [14]. This same order was also observed in terms of overall selection pressure, measured as the mean ratio of nonsynonymous (dN) to synonymous substitutions (dS) per site (dN/dS), estimated using the maximum likelihood SLAC (Single Likelihood Ancestor Counting; http://www.datamonkey.org/) method [24]: N = 0.048; L = 0.055; M = 0.078; G = 0.119; P = 0.187. This approximately four-fold difference in mean dN/dS reflects major differences in selective constraint among proteins. This trend was also reflected in previous analyses of full length genomes of vaccine strains [22] and through partial gene comparisons [25], [26].

Bottom Line: To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution.In doing so we significantly increase the extent of genome sequence data available for these important viruses.A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats.

View Article: PubMed Central - PubMed

Affiliation: Institut Pasteur, UPRE Lyssavirus Dynamics and Host Adaptation, World Health Organization Collaborating Centre for Reference and Research on Rabies, Paris, France.

ABSTRACT
Lyssaviruses are RNA viruses with single-strand, negative-sense genomes responsible for rabies-like diseases in mammals. To date, genomic and evolutionary studies have most often utilized partial genome sequences, particularly of the nucleoprotein and glycoprotein genes, with little consideration of genome-scale evolution. Herein, we report the first genomic and evolutionary analysis using complete genome sequences of all recognised lyssavirus genotypes, including 14 new complete genomes of field isolates from 6 genotypes and one genotype that is completely sequenced for the first time. In doing so we significantly increase the extent of genome sequence data available for these important viruses. Our analysis of these genome sequence data reveals that all lyssaviruses have the same genomic organization. A phylogenetic analysis reveals strong geographical structuring, with the greatest genetic diversity in Africa, and an independent origin for the two known genotypes that infect European bats. We also suggest that multiple genotypes may exist within the diversity of viruses currently classified as 'Lagos Bat'. In sum, we show that rigorous phylogenetic techniques based on full length genome sequence provide the best discriminatory power for genotype classification within the lyssaviruses.

Show MeSH
Related in: MedlinePlus