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Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

Carnes J, Anupama A, Balmer O, Jackson A, Lewis M, Brown R, Cestari I, Desquesnes M, Gendrin C, Hertz-Fowler C, Imamura H, Ivens A, Kořený L, Lai DH, MacLeod A, McDermott SM, Merritt C, Monnerat S, Moon W, Myler P, Phan I, Ramasamy G, Sivam D, Lun ZR, Lukeš J, Stuart K, Schnaufer A - PLoS Negl Trop Dis (2015)

Bottom Line: Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality.Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA.Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Seattle Biomedical Research Institute, Seattle, United States of America.

ABSTRACT
Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

No MeSH data available.


Related in: MedlinePlus

Diversity of a-type and b-type VSG between T. b. brucei TREU 927/4 and T. evansi STIB805 compared.Histograms showing a-type VSG (A.) or b-type VSG (B.) distributions of strain-specific clade size in T. b. brucei (black bars) and T. evansi (red bars) as defined by the phylogeny (see S10 Fig.). Frequency distributions of a-type VSG (C.) or b-type VSG (D.) synonymous (Ks) and non-synonymous (Ka) substitution rates per site, and the ω (Ka/Ks) for orthologous pairs of VSG (a-type n = 151; b-type n = 112), as defined by the phylogeny, in relation to values for unambiguous non-VSG orthologous pairs (n = 6331).
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pntd-0003404-g004: Diversity of a-type and b-type VSG between T. b. brucei TREU 927/4 and T. evansi STIB805 compared.Histograms showing a-type VSG (A.) or b-type VSG (B.) distributions of strain-specific clade size in T. b. brucei (black bars) and T. evansi (red bars) as defined by the phylogeny (see S10 Fig.). Frequency distributions of a-type VSG (C.) or b-type VSG (D.) synonymous (Ks) and non-synonymous (Ka) substitution rates per site, and the ω (Ka/Ks) for orthologous pairs of VSG (a-type n = 151; b-type n = 112), as defined by the phylogeny, in relation to values for unambiguous non-VSG orthologous pairs (n = 6331).

Mentions: The predicted protein structures of VSGs in T. evansi STIB805 conform to the canonical structures in T. b. brucei and T. b. gambiense, and include all five recognized N-terminal sub-types (N1-5). In T. evansi STIB805 we identified 525 a-type VSGs (i.e. N-1-3 and 5; S2 Data File) and 505 b-type VSGs (i.e. N4; S3 Data File); of these 453 (86%) and 451 (89%), respectively, are full-length. Given that the assembly of subtelomeric and mini-chromosomal regions is fragmentary, these numbers may underestimate the real number of VSGs, although the total is comparable with both T. b. brucei TREU 927/4 [22] and T. b. gambiense DAL972 sequences [33]. The VSG repertoire is largely conserved between the T. b. brucei TREU 927/4 reference and T. evansi STIB805, as the VSGs are interspersed among each other in neighbour-joining molecular cladograms (S10 Fig.). Another indication of the similarity of the VSG repertoire is that very few clades of strain-specific VSG are larger than 2–3 (Fig. 4a and b). Large clades of VSG from a single genome would suggest divergence of VSG repertoire through gene duplication. Hence, 376 and 384 ( = 85.1%) T. evansi STIB805 and T. b. brucei TREU 927/4 a-VSGs, respectively, are most closely related to an ortholog in the other strain, or are paraphyletic to a clade of such sequences (i.e. strain-specific clade size  = 1). Only 40 T. evansi STIB805 VSGs and 51 T. b. brucei TREU 927/4 VSGs form a clade with a paralog from the same genome (i.e. strain-specific clade size  = 2), suggesting a single gene duplication since the strains separated. The same patterns occur with b-VSGs. Orthology between VSGs does not mean that they are unaffected by recombination, only that enough sequence homology persists for two orthologs to cluster together. Indeed, among 151 putative a-VSG orthologs 33 (21.8%) have dissimilar C-terminal types, while among 112 b-VSG orthologs 32 (28.6%) showed similar evidence for recombination having occurred since these two strains split from their common ancestor. Thus, analysis of the VSG repertoire reveals no evidence for the evolution of specific VSG gene clusters or subfamilies in T. evansi, similar to what had been observed for T. b. gambiense[33].


Genome and phylogenetic analyses of Trypanosoma evansi reveal extensive similarity to T. brucei and multiple independent origins for dyskinetoplasty.

Carnes J, Anupama A, Balmer O, Jackson A, Lewis M, Brown R, Cestari I, Desquesnes M, Gendrin C, Hertz-Fowler C, Imamura H, Ivens A, Kořený L, Lai DH, MacLeod A, McDermott SM, Merritt C, Monnerat S, Moon W, Myler P, Phan I, Ramasamy G, Sivam D, Lun ZR, Lukeš J, Stuart K, Schnaufer A - PLoS Negl Trop Dis (2015)

Diversity of a-type and b-type VSG between T. b. brucei TREU 927/4 and T. evansi STIB805 compared.Histograms showing a-type VSG (A.) or b-type VSG (B.) distributions of strain-specific clade size in T. b. brucei (black bars) and T. evansi (red bars) as defined by the phylogeny (see S10 Fig.). Frequency distributions of a-type VSG (C.) or b-type VSG (D.) synonymous (Ks) and non-synonymous (Ka) substitution rates per site, and the ω (Ka/Ks) for orthologous pairs of VSG (a-type n = 151; b-type n = 112), as defined by the phylogeny, in relation to values for unambiguous non-VSG orthologous pairs (n = 6331).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4288722&req=5

pntd-0003404-g004: Diversity of a-type and b-type VSG between T. b. brucei TREU 927/4 and T. evansi STIB805 compared.Histograms showing a-type VSG (A.) or b-type VSG (B.) distributions of strain-specific clade size in T. b. brucei (black bars) and T. evansi (red bars) as defined by the phylogeny (see S10 Fig.). Frequency distributions of a-type VSG (C.) or b-type VSG (D.) synonymous (Ks) and non-synonymous (Ka) substitution rates per site, and the ω (Ka/Ks) for orthologous pairs of VSG (a-type n = 151; b-type n = 112), as defined by the phylogeny, in relation to values for unambiguous non-VSG orthologous pairs (n = 6331).
Mentions: The predicted protein structures of VSGs in T. evansi STIB805 conform to the canonical structures in T. b. brucei and T. b. gambiense, and include all five recognized N-terminal sub-types (N1-5). In T. evansi STIB805 we identified 525 a-type VSGs (i.e. N-1-3 and 5; S2 Data File) and 505 b-type VSGs (i.e. N4; S3 Data File); of these 453 (86%) and 451 (89%), respectively, are full-length. Given that the assembly of subtelomeric and mini-chromosomal regions is fragmentary, these numbers may underestimate the real number of VSGs, although the total is comparable with both T. b. brucei TREU 927/4 [22] and T. b. gambiense DAL972 sequences [33]. The VSG repertoire is largely conserved between the T. b. brucei TREU 927/4 reference and T. evansi STIB805, as the VSGs are interspersed among each other in neighbour-joining molecular cladograms (S10 Fig.). Another indication of the similarity of the VSG repertoire is that very few clades of strain-specific VSG are larger than 2–3 (Fig. 4a and b). Large clades of VSG from a single genome would suggest divergence of VSG repertoire through gene duplication. Hence, 376 and 384 ( = 85.1%) T. evansi STIB805 and T. b. brucei TREU 927/4 a-VSGs, respectively, are most closely related to an ortholog in the other strain, or are paraphyletic to a clade of such sequences (i.e. strain-specific clade size  = 1). Only 40 T. evansi STIB805 VSGs and 51 T. b. brucei TREU 927/4 VSGs form a clade with a paralog from the same genome (i.e. strain-specific clade size  = 2), suggesting a single gene duplication since the strains separated. The same patterns occur with b-VSGs. Orthology between VSGs does not mean that they are unaffected by recombination, only that enough sequence homology persists for two orthologs to cluster together. Indeed, among 151 putative a-VSG orthologs 33 (21.8%) have dissimilar C-terminal types, while among 112 b-VSG orthologs 32 (28.6%) showed similar evidence for recombination having occurred since these two strains split from their common ancestor. Thus, analysis of the VSG repertoire reveals no evidence for the evolution of specific VSG gene clusters or subfamilies in T. evansi, similar to what had been observed for T. b. gambiense[33].

Bottom Line: Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality.Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA.Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

View Article: PubMed Central - PubMed

Affiliation: Seattle Biomedical Research Institute, Seattle, United States of America.

ABSTRACT
Two key biological features distinguish Trypanosoma evansi from the T. brucei group: independence from the tsetse fly as obligatory vector, and independence from the need for functional mitochondrial DNA (kinetoplast or kDNA). In an effort to better understand the molecular causes and consequences of these differences, we sequenced the genome of an akinetoplastic T. evansi strain from China and compared it to the T. b. brucei reference strain. The annotated T. evansi genome shows extensive similarity to the reference, with 94.9% of the predicted T. b. brucei coding sequences (CDS) having an ortholog in T. evansi, and 94.6% of the non-repetitive orthologs having a nucleotide identity of 95% or greater. Interestingly, several procyclin-associated genes (PAGs) were disrupted or not found in this T. evansi strain, suggesting a selective loss of function in the absence of the insect life-cycle stage. Surprisingly, orthologous sequences were found in T. evansi for all 978 nuclear CDS predicted to represent the mitochondrial proteome in T. brucei, although a small number of these may have lost functionality. Consistent with previous results, the F1FO-ATP synthase γ subunit was found to have an A281 deletion, which is involved in generation of a mitochondrial membrane potential in the absence of kDNA. Candidates for CDS that are absent from the reference genome were identified in supplementary de novo assemblies of T. evansi reads. Phylogenetic analyses show that the sequenced strain belongs to a dominant group of clonal T. evansi strains with worldwide distribution that also includes isolates classified as T. equiperdum. At least three other types of T. evansi or T. equiperdum have emerged independently. Overall, the elucidation of the T. evansi genome sequence reveals extensive similarity of T. brucei and supports the contention that T. evansi should be classified as a subspecies of T. brucei.

No MeSH data available.


Related in: MedlinePlus