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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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Comparison of gene order at three regions of chromosomal rearrangement. Forward and reverse strand are represented by horizontal bars, colour-coded by species (purple: Babesia divergens 1802A; green: Babesia bigemina BOND; blue: Babesia bovis T2Bo). Genes are indicated by boxes within reading frames. ves-like gene models are colour-coded as indicated by the key. Vertical grey bars between genomes represent significant BLASTn hits as calculated in ACT. (A) The region spanning 1154–1238kb of chromosome 1 in B. bigemina, which corresponds to chromosomal breakpoints in both other species. (B) The region spanning 302–364 kb of chromosome 2 in B. bigemina, which corresponds to a chromosomal breakpoint in B. divergens. (C) The region spanning 975–1335 kb of chromosome 3 in B. bigemina that is conserved in both other species but which has experienced numerous B. bigemina-specific insertions of BbigVes1b genes (shaded blue). The genomic locations of regions a-c are shown in Supplementary Figure S1A/B.
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Figure 2: Comparison of gene order at three regions of chromosomal rearrangement. Forward and reverse strand are represented by horizontal bars, colour-coded by species (purple: Babesia divergens 1802A; green: Babesia bigemina BOND; blue: Babesia bovis T2Bo). Genes are indicated by boxes within reading frames. ves-like gene models are colour-coded as indicated by the key. Vertical grey bars between genomes represent significant BLASTn hits as calculated in ACT. (A) The region spanning 1154–1238kb of chromosome 1 in B. bigemina, which corresponds to chromosomal breakpoints in both other species. (B) The region spanning 302–364 kb of chromosome 2 in B. bigemina, which corresponds to a chromosomal breakpoint in B. divergens. (C) The region spanning 975–1335 kb of chromosome 3 in B. bigemina that is conserved in both other species but which has experienced numerous B. bigemina-specific insertions of BbigVes1b genes (shaded blue). The genomic locations of regions a-c are shown in Supplementary Figure S1A/B.

Mentions: By mapping sequence scaffolds to the B. bovis genome, we determined that B. bigemina BOND has four chromosomes, as suggested previously (70); however, these are not co-linear with B. bovis chromosomes. Sequence alignment based on conserved gene order demonstrates that segmental inversion and chromosomal rearrangement have been very frequent since these Babesia species separated. Supplementary Figure S1A/B aligns various sequence blocks from the B. bovis T2Bo and B. divergens 1802A genomes that correspond to full-length chromosomes in B. bigemina BOND. The positions of coding sequences homologous to B. bovis ves1 genes are marked and these coincide with chromosomal breakpoints. When we inspect breakpoints in co-linearity more closely, as shown in Figure 2, ves-like genes occur at homologous positions in all three genomes, but it is clear that these homologs have quite different size and orientation (Figure 2a). Other multi-copy genes (shaded yellow) also congregate at similar positions (Figure 2b), reminiscent of the proximity of smORF to ves1 in B. bovis T2Bo (22). In addition, and somewhat anomalously, B. bigemina BOND has 28 ves1b loci on chromosome 3 at positions not associated with genome rearrangements, which likely represent lineage-specific insertion events (Figure 2c). The presence of ves-like genes at corresponding positions in different Babesia species may be ancestral, (i.e. these genes are orthologs, descended directly from a progenitor at the same position in the ancestral genome), or it may be mechanistic, (i.e. these positions are prone to rearrangement in all species and ves-like genes, which are not orthologous, independently transpose to them as regions in which purifying selection is weak).


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)

Comparison of gene order at three regions of chromosomal rearrangement. Forward and reverse strand are represented by horizontal bars, colour-coded by species (purple: Babesia divergens 1802A; green: Babesia bigemina BOND; blue: Babesia bovis T2Bo). Genes are indicated by boxes within reading frames. ves-like gene models are colour-coded as indicated by the key. Vertical grey bars between genomes represent significant BLASTn hits as calculated in ACT. (A) The region spanning 1154–1238kb of chromosome 1 in B. bigemina, which corresponds to chromosomal breakpoints in both other species. (B) The region spanning 302–364 kb of chromosome 2 in B. bigemina, which corresponds to a chromosomal breakpoint in B. divergens. (C) The region spanning 975–1335 kb of chromosome 3 in B. bigemina that is conserved in both other species but which has experienced numerous B. bigemina-specific insertions of BbigVes1b genes (shaded blue). The genomic locations of regions a-c are shown in Supplementary Figure S1A/B.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: Comparison of gene order at three regions of chromosomal rearrangement. Forward and reverse strand are represented by horizontal bars, colour-coded by species (purple: Babesia divergens 1802A; green: Babesia bigemina BOND; blue: Babesia bovis T2Bo). Genes are indicated by boxes within reading frames. ves-like gene models are colour-coded as indicated by the key. Vertical grey bars between genomes represent significant BLASTn hits as calculated in ACT. (A) The region spanning 1154–1238kb of chromosome 1 in B. bigemina, which corresponds to chromosomal breakpoints in both other species. (B) The region spanning 302–364 kb of chromosome 2 in B. bigemina, which corresponds to a chromosomal breakpoint in B. divergens. (C) The region spanning 975–1335 kb of chromosome 3 in B. bigemina that is conserved in both other species but which has experienced numerous B. bigemina-specific insertions of BbigVes1b genes (shaded blue). The genomic locations of regions a-c are shown in Supplementary Figure S1A/B.
Mentions: By mapping sequence scaffolds to the B. bovis genome, we determined that B. bigemina BOND has four chromosomes, as suggested previously (70); however, these are not co-linear with B. bovis chromosomes. Sequence alignment based on conserved gene order demonstrates that segmental inversion and chromosomal rearrangement have been very frequent since these Babesia species separated. Supplementary Figure S1A/B aligns various sequence blocks from the B. bovis T2Bo and B. divergens 1802A genomes that correspond to full-length chromosomes in B. bigemina BOND. The positions of coding sequences homologous to B. bovis ves1 genes are marked and these coincide with chromosomal breakpoints. When we inspect breakpoints in co-linearity more closely, as shown in Figure 2, ves-like genes occur at homologous positions in all three genomes, but it is clear that these homologs have quite different size and orientation (Figure 2a). Other multi-copy genes (shaded yellow) also congregate at similar positions (Figure 2b), reminiscent of the proximity of smORF to ves1 in B. bovis T2Bo (22). In addition, and somewhat anomalously, B. bigemina BOND has 28 ves1b loci on chromosome 3 at positions not associated with genome rearrangements, which likely represent lineage-specific insertion events (Figure 2c). The presence of ves-like genes at corresponding positions in different Babesia species may be ancestral, (i.e. these genes are orthologs, descended directly from a progenitor at the same position in the ancestral genome), or it may be mechanistic, (i.e. these positions are prone to rearrangement in all species and ves-like genes, which are not orthologous, independently transpose to them as regions in which purifying selection is weak).

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