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The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.

Jackson AP, Otto TD, Darby A, Ramaprasad A, Xia D, Echaide IE, Farber M, Gahlot S, Gamble J, Gupta D, Gupta Y, Jackson L, Malandrin L, Malas TB, Moussa E, Nair M, Reid AJ, Sanders M, Sharma J, Tracey A, Quail MA, Weir W, Wastling JM, Hall N, Willadsen P, Lingelbach K, Shiels B, Tait A, Berriman M, Allred DR, Pain A - Nucleic Acids Res. (2014)

Bottom Line: Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families.Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family.Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK a.p.jackson@liv.ac.uk.

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(A) Unrooted maximum likelihood phylogeny of ves1 genes from Babesia spp. based on a multiple nucleotide sequence alignment corresponding to the conserved C-terminal domain of VESA1 only (840 characters). A GTR+Γ model was applied. Support for principal nodes is indicated by non-parametric bootstraps and posterior probabilities from a Bayesian analysis using the same model. (B) Sequence similarity network based on FASTA scores generated from pair-wise comparisons of VESA1 and VESA2 amino acid sequences and generated using BioLayout Express v3.0. Individual sequences are represented by spheres, shaded by gene family, connected by lines that represent sequence homology. The network was organized such that spheres edge length is minimized and spheres are positioned nearest to their closest relatives. A lower threshold has been applied to exclude poor sequence matches, leaving only the strongest similarities as determined by FASTA. SMORF sequences were included, but no FASTA scores exceeded the threshold. Ves-like gene families are labelled as described in the text; a single Babesia bovis sequence that clusters close to BbigVes2 (BBOV_III002580) is shown with a red circle.
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Figure 4: (A) Unrooted maximum likelihood phylogeny of ves1 genes from Babesia spp. based on a multiple nucleotide sequence alignment corresponding to the conserved C-terminal domain of VESA1 only (840 characters). A GTR+Γ model was applied. Support for principal nodes is indicated by non-parametric bootstraps and posterior probabilities from a Bayesian analysis using the same model. (B) Sequence similarity network based on FASTA scores generated from pair-wise comparisons of VESA1 and VESA2 amino acid sequences and generated using BioLayout Express v3.0. Individual sequences are represented by spheres, shaded by gene family, connected by lines that represent sequence homology. The network was organized such that spheres edge length is minimized and spheres are positioned nearest to their closest relatives. A lower threshold has been applied to exclude poor sequence matches, leaving only the strongest similarities as determined by FASTA. SMORF sequences were included, but no FASTA scores exceeded the threshold. Ves-like gene families are labelled as described in the text; a single Babesia bovis sequence that clusters close to BbigVes2 (BBOV_III002580) is shown with a red circle.

Mentions: In B. bigemina BOND there are two families homologous to ves1 that are approximately equally abundant; we refer to these families as BbigVes1a (N = 74) and BbigVes1b (N = 80). While ∼70% of B. bovis ves1 are arranged in putative LATs consisting of both ves1 types (26), these homologs are similarly arranged in only 35% of cases in B. bigemina BOND. Indeed, the phylogeny of all ves1 genes (see Figure 4 below) indicates that these homologs in B. bigemina are not orthologous to the ves1α and ves1β of B. bovis. Sixteen gene copies (‘BbigVes1ba’) appear to be recombinant ves1b, with ves1a-type 3′ ends. We found no smORF homologs in B. bigemina.


The evolutionary dynamics of variant antigen genes in Babesia reveal a history of genomic innovation underlying host-parasite interaction.

Jackson AP, Otto TD, Darby A, Ramaprasad A, Xia D, Echaide IE, Farber M, Gahlot S, Gamble J, Gupta D, Gupta Y, Jackson L, Malandrin L, Malas TB, Moussa E, Nair M, Reid AJ, Sanders M, Sharma J, Tracey A, Quail MA, Weir W, Wastling JM, Hall N, Willadsen P, Lingelbach K, Shiels B, Tait A, Berriman M, Allred DR, Pain A - Nucleic Acids Res. (2014)

(A) Unrooted maximum likelihood phylogeny of ves1 genes from Babesia spp. based on a multiple nucleotide sequence alignment corresponding to the conserved C-terminal domain of VESA1 only (840 characters). A GTR+Γ model was applied. Support for principal nodes is indicated by non-parametric bootstraps and posterior probabilities from a Bayesian analysis using the same model. (B) Sequence similarity network based on FASTA scores generated from pair-wise comparisons of VESA1 and VESA2 amino acid sequences and generated using BioLayout Express v3.0. Individual sequences are represented by spheres, shaded by gene family, connected by lines that represent sequence homology. The network was organized such that spheres edge length is minimized and spheres are positioned nearest to their closest relatives. A lower threshold has been applied to exclude poor sequence matches, leaving only the strongest similarities as determined by FASTA. SMORF sequences were included, but no FASTA scores exceeded the threshold. Ves-like gene families are labelled as described in the text; a single Babesia bovis sequence that clusters close to BbigVes2 (BBOV_III002580) is shown with a red circle.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4066756&req=5

Figure 4: (A) Unrooted maximum likelihood phylogeny of ves1 genes from Babesia spp. based on a multiple nucleotide sequence alignment corresponding to the conserved C-terminal domain of VESA1 only (840 characters). A GTR+Γ model was applied. Support for principal nodes is indicated by non-parametric bootstraps and posterior probabilities from a Bayesian analysis using the same model. (B) Sequence similarity network based on FASTA scores generated from pair-wise comparisons of VESA1 and VESA2 amino acid sequences and generated using BioLayout Express v3.0. Individual sequences are represented by spheres, shaded by gene family, connected by lines that represent sequence homology. The network was organized such that spheres edge length is minimized and spheres are positioned nearest to their closest relatives. A lower threshold has been applied to exclude poor sequence matches, leaving only the strongest similarities as determined by FASTA. SMORF sequences were included, but no FASTA scores exceeded the threshold. Ves-like gene families are labelled as described in the text; a single Babesia bovis sequence that clusters close to BbigVes2 (BBOV_III002580) is shown with a red circle.
Mentions: In B. bigemina BOND there are two families homologous to ves1 that are approximately equally abundant; we refer to these families as BbigVes1a (N = 74) and BbigVes1b (N = 80). While ∼70% of B. bovis ves1 are arranged in putative LATs consisting of both ves1 types (26), these homologs are similarly arranged in only 35% of cases in B. bigemina BOND. Indeed, the phylogeny of all ves1 genes (see Figure 4 below) indicates that these homologs in B. bigemina are not orthologous to the ves1α and ves1β of B. bovis. Sixteen gene copies (‘BbigVes1ba’) appear to be recombinant ves1b, with ves1a-type 3′ ends. We found no smORF homologs in B. bigemina.

Bottom Line: Similarly, analysis of sequence mosaicism shows that recombination drives variation in ves1 sequences, but less so for ves2, indicating the adoption of different mechanisms for variation of the two families.Proteomic analysis of the B. bigemina PR isolate shows that two dominant VESA1 proteins are expressed in the population, whereas numerous VESA2 proteins are co-expressed, consistent with differential transcriptional regulation of each family.Hence, VESA2 proteins are abundant and previously unrecognized elements of Babesia biology, with evolutionary dynamics consistently different to those of VESA1, suggesting that their functions are distinct.

View Article: PubMed Central - PubMed

Affiliation: Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool Science Park Ic2, 146 Brownlow Hill, Liverpool L3 5RF, UK a.p.jackson@liv.ac.uk.

Show MeSH