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Chromosomal copy number variation reveals differential levels of genomic plasticity in distinct Trypanosoma cruzi strains.

Reis-Cunha JL, Rodrigues-Luiz GF, Valdivia HO, Baptista RP, Mendes TA, de Morais GL, Guedes R, Macedo AM, Bern C, Gilman RH, Lopez CT, Andersson B, Vasconcelos AT, Bartholomeu DC - BMC Genomics (2015)

Bottom Line: Although the T. cruzi karyotype is not well defined, several studies have demonstrated a significant variation in the size and content of chromosomes between different T. cruzi strains.Chromosome 31, which is the only chromosome that is supernumerary in all six T. cruzi samples evaluated in this study, is enriched with genes related to glycosylation pathways, highlighting the importance of glycosylation to parasite survival.Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression, which represents a strategy that may be crucial for parasites that mainly depend on post-transcriptional mechanisms to control gene expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunologia e Genômica de Parasitos, Departamento deParasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. jaumlrc@gmail.com.

ABSTRACT

Background: Trypanosoma cruzi, the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. CL Brener, the reference strain of the T. cruzi genome project, is a hybrid with a genome assembled into 41 putative chromosomes. Gene copy number variation (CNV) is well documented as an important mechanism to enhance gene expression and variability in T. cruzi. Chromosomal CNV (CCNV) is another level of gene CNV in which whole blocks of genes are expanded simultaneously. Although the T. cruzi karyotype is not well defined, several studies have demonstrated a significant variation in the size and content of chromosomes between different T. cruzi strains. Despite these studies, the extent of diversity in CCNV among T. cruzi strains based on a read depth coverage analysis has not been determined.

Results: We identify the CCNV in T. cruzi strains from the TcI, TcII and TcIII DTUs, by analyzing the depth coverage of short reads from these strains using the 41 CL Brener chromosomes as reference. This study led to the identification of a broader extent of CCNV in T. cruzi than was previously speculated. The TcI DTU strains have very few aneuploidies, while the strains from TcII and TcIII DTUs present a high degree of chromosomal expansions. Chromosome 31, which is the only chromosome that is supernumerary in all six T. cruzi samples evaluated in this study, is enriched with genes related to glycosylation pathways, highlighting the importance of glycosylation to parasite survival.

Conclusions: Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression, which represents a strategy that may be crucial for parasites that mainly depend on post-transcriptional mechanisms to control gene expression.

No MeSH data available.


Related in: MedlinePlus

Correspondence between the ploidy predicted by the SCoPE approach and the normalized read depth coverage (RDC) along the entire chromosome sequences. The correspondence between the chromosomal ploidy and the normalized read depth coverage of chromosomes 16 (red box), 27 (blue box) and 31 (green box) of the T. cruzi Y strain is shown. a Chromosomal ploidy predicted by the SCoPE approach. b The blue line corresponds to the normalized RDC of each position, estimated by the ratio between the RDC and the genome coverage. Below, the protein-coding genes are depicted as rectangles drawn as proportional to their length, and their coding strand is indicated by their position above (top strand) or below (bottom strand) the central line. Cyan and black rectangles represent multigene families and hypothetical/housekeeping genes, respectively. Gaps are represented by gene-less regions with no read coverage. Chromosome 16 was predicted as disomic, 27 as trisomic and 31 as tetrasomic. The regions of low coverage correspond to regions rich in multigene families or chromosomal gap regions. c The predicted ploidy based on the proportion of the alleles in the heterozygous SNP positions for chromosomes 16, 27 and 31 is shown. The peak of 0.5 classifies chromosome 16 as diploid, the peaks of 0.3 and 0.6 classify chromosome 27 as triploid, and the peaks of 0.2-0.8 and 0.5 classify chromosome 31 as tetraploid
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Fig4: Correspondence between the ploidy predicted by the SCoPE approach and the normalized read depth coverage (RDC) along the entire chromosome sequences. The correspondence between the chromosomal ploidy and the normalized read depth coverage of chromosomes 16 (red box), 27 (blue box) and 31 (green box) of the T. cruzi Y strain is shown. a Chromosomal ploidy predicted by the SCoPE approach. b The blue line corresponds to the normalized RDC of each position, estimated by the ratio between the RDC and the genome coverage. Below, the protein-coding genes are depicted as rectangles drawn as proportional to their length, and their coding strand is indicated by their position above (top strand) or below (bottom strand) the central line. Cyan and black rectangles represent multigene families and hypothetical/housekeeping genes, respectively. Gaps are represented by gene-less regions with no read coverage. Chromosome 16 was predicted as disomic, 27 as trisomic and 31 as tetrasomic. The regions of low coverage correspond to regions rich in multigene families or chromosomal gap regions. c The predicted ploidy based on the proportion of the alleles in the heterozygous SNP positions for chromosomes 16, 27 and 31 is shown. The peak of 0.5 classifies chromosome 16 as diploid, the peaks of 0.3 and 0.6 classify chromosome 27 as triploid, and the peaks of 0.2-0.8 and 0.5 classify chromosome 31 as tetraploid

Mentions: To evaluate if these predicted aneuploidies were produced by the gain or loss of a whole chromosome, or if they result from segmental duplication or loss of partial fragments from these chromosomes, the normalized read depth coverage of each position along each chromosome of the six T. cruzi strains was estimated (Additional file 4: Figure S2). Figure 4 represents the read depth coverage along each position of the predicted disomic, trisomic and tetrasomic chromosomes of the Y strain, as well as the base frequency distribution between the heterozygous SNP positions. As expected, with the exception of the regions that are rich in multigene families and gaps, the predicted ploidy along the entire chromosome is in agreement with the predicted ploidy based on the SCoPE and SNP analyses. This finding suggests that these aneuploidies are probably a result of a whole chromosomal duplication/loss.Fig. 4


Chromosomal copy number variation reveals differential levels of genomic plasticity in distinct Trypanosoma cruzi strains.

Reis-Cunha JL, Rodrigues-Luiz GF, Valdivia HO, Baptista RP, Mendes TA, de Morais GL, Guedes R, Macedo AM, Bern C, Gilman RH, Lopez CT, Andersson B, Vasconcelos AT, Bartholomeu DC - BMC Genomics (2015)

Correspondence between the ploidy predicted by the SCoPE approach and the normalized read depth coverage (RDC) along the entire chromosome sequences. The correspondence between the chromosomal ploidy and the normalized read depth coverage of chromosomes 16 (red box), 27 (blue box) and 31 (green box) of the T. cruzi Y strain is shown. a Chromosomal ploidy predicted by the SCoPE approach. b The blue line corresponds to the normalized RDC of each position, estimated by the ratio between the RDC and the genome coverage. Below, the protein-coding genes are depicted as rectangles drawn as proportional to their length, and their coding strand is indicated by their position above (top strand) or below (bottom strand) the central line. Cyan and black rectangles represent multigene families and hypothetical/housekeeping genes, respectively. Gaps are represented by gene-less regions with no read coverage. Chromosome 16 was predicted as disomic, 27 as trisomic and 31 as tetrasomic. The regions of low coverage correspond to regions rich in multigene families or chromosomal gap regions. c The predicted ploidy based on the proportion of the alleles in the heterozygous SNP positions for chromosomes 16, 27 and 31 is shown. The peak of 0.5 classifies chromosome 16 as diploid, the peaks of 0.3 and 0.6 classify chromosome 27 as triploid, and the peaks of 0.2-0.8 and 0.5 classify chromosome 31 as tetraploid
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Related In: Results  -  Collection

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Fig4: Correspondence between the ploidy predicted by the SCoPE approach and the normalized read depth coverage (RDC) along the entire chromosome sequences. The correspondence between the chromosomal ploidy and the normalized read depth coverage of chromosomes 16 (red box), 27 (blue box) and 31 (green box) of the T. cruzi Y strain is shown. a Chromosomal ploidy predicted by the SCoPE approach. b The blue line corresponds to the normalized RDC of each position, estimated by the ratio between the RDC and the genome coverage. Below, the protein-coding genes are depicted as rectangles drawn as proportional to their length, and their coding strand is indicated by their position above (top strand) or below (bottom strand) the central line. Cyan and black rectangles represent multigene families and hypothetical/housekeeping genes, respectively. Gaps are represented by gene-less regions with no read coverage. Chromosome 16 was predicted as disomic, 27 as trisomic and 31 as tetrasomic. The regions of low coverage correspond to regions rich in multigene families or chromosomal gap regions. c The predicted ploidy based on the proportion of the alleles in the heterozygous SNP positions for chromosomes 16, 27 and 31 is shown. The peak of 0.5 classifies chromosome 16 as diploid, the peaks of 0.3 and 0.6 classify chromosome 27 as triploid, and the peaks of 0.2-0.8 and 0.5 classify chromosome 31 as tetraploid
Mentions: To evaluate if these predicted aneuploidies were produced by the gain or loss of a whole chromosome, or if they result from segmental duplication or loss of partial fragments from these chromosomes, the normalized read depth coverage of each position along each chromosome of the six T. cruzi strains was estimated (Additional file 4: Figure S2). Figure 4 represents the read depth coverage along each position of the predicted disomic, trisomic and tetrasomic chromosomes of the Y strain, as well as the base frequency distribution between the heterozygous SNP positions. As expected, with the exception of the regions that are rich in multigene families and gaps, the predicted ploidy along the entire chromosome is in agreement with the predicted ploidy based on the SCoPE and SNP analyses. This finding suggests that these aneuploidies are probably a result of a whole chromosomal duplication/loss.Fig. 4

Bottom Line: Although the T. cruzi karyotype is not well defined, several studies have demonstrated a significant variation in the size and content of chromosomes between different T. cruzi strains.Chromosome 31, which is the only chromosome that is supernumerary in all six T. cruzi samples evaluated in this study, is enriched with genes related to glycosylation pathways, highlighting the importance of glycosylation to parasite survival.Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression, which represents a strategy that may be crucial for parasites that mainly depend on post-transcriptional mechanisms to control gene expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratório de Imunologia e Genômica de Parasitos, Departamento deParasitologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. jaumlrc@gmail.com.

ABSTRACT

Background: Trypanosoma cruzi, the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. CL Brener, the reference strain of the T. cruzi genome project, is a hybrid with a genome assembled into 41 putative chromosomes. Gene copy number variation (CNV) is well documented as an important mechanism to enhance gene expression and variability in T. cruzi. Chromosomal CNV (CCNV) is another level of gene CNV in which whole blocks of genes are expanded simultaneously. Although the T. cruzi karyotype is not well defined, several studies have demonstrated a significant variation in the size and content of chromosomes between different T. cruzi strains. Despite these studies, the extent of diversity in CCNV among T. cruzi strains based on a read depth coverage analysis has not been determined.

Results: We identify the CCNV in T. cruzi strains from the TcI, TcII and TcIII DTUs, by analyzing the depth coverage of short reads from these strains using the 41 CL Brener chromosomes as reference. This study led to the identification of a broader extent of CCNV in T. cruzi than was previously speculated. The TcI DTU strains have very few aneuploidies, while the strains from TcII and TcIII DTUs present a high degree of chromosomal expansions. Chromosome 31, which is the only chromosome that is supernumerary in all six T. cruzi samples evaluated in this study, is enriched with genes related to glycosylation pathways, highlighting the importance of glycosylation to parasite survival.

Conclusions: Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression, which represents a strategy that may be crucial for parasites that mainly depend on post-transcriptional mechanisms to control gene expression.

No MeSH data available.


Related in: MedlinePlus