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Concerted evolution at a multicopy locus in the protozoan parasite Theileria parva: extreme divergence of potential protein-coding sequences.

ABSTRACT: Concerted evolution of multicopy gene families in vertebrates is recognized as an important force in the generation of biological novelty but has not been documented for the multicopy genes of protozoa. A multicopy locus, Tpr, which consists of tandemly arrayed open reading frames (ORFs) containing several repeated elements has been described for Theileria parva. Herein we show that probes derived from the 5'/N-terminal ends of ORFs in the genomic DNAs of T. parva Uganda (1,108 codons) and Boleni (699 codons) hybridized with multicopy sequences in homologous DNA but did not detect similar sequences in the DNA of 14 heterologous T. parva stocks and clones. The probe sequences were, however, protein coding according to predictive algorithms and codon usage. The 3'/C-terminal ends of the Uganda and Boleni ORFs exhibited 75% similarity and identity, respectively, to the previously identified Tpr1 and Tpr2 repetitive elements of T. parva Muguga. Tpr1-homologous sequences were detected in two additional species of Theileria. Eight different Tpr1-homologous transcripts were present in piroplasm mRNA from a single T. parva Muguga-infected animal. The Tpr1 and Tpr2 amino acid sequences contained six predicted membrane-associated segments. The ratio of synonymous to nonsynonymous substitutions indicates that Tpr1 evolves like protein-encoding DNA. The previously determined nucleotide sequence of the gene encoding the p67 antigen is completely identical in T. parva Muguga, Boleni, and Uganda, including the third base in codons. The data suggest that concerted evolution can lead to the radical divergence of coding sequences and that this can be a mechanism for the generation of novel genes.

SUBMITTER: Bishop R

PROVIDER: S-EPMC231891 | biostudies-other | 1997 Mar

REPOSITORIES: biostudies-other

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Concerted evolution at a multicopy locus in the protozoan parasite Theileria parva: extreme divergence of potential protein-coding sequences.

Bishop R R Musoke A A Morzaria S S Sohanpal B B Gobright E E

Molecular and cellular biology 19970301 3

Concerted evolution of multicopy gene families in vertebrates is recognized as an important force in the generation of biological novelty but has not been documented for the multicopy genes of protozoa. A multicopy locus, Tpr, which consists of tandemly arrayed open reading frames (ORFs) containing several repeated elements has been described for Theileria parva. Herein we show that probes derived from the 5'/N-terminal ends of ORFs in the genomic DNAs of T. parva Uganda (1,108 codons) and Bolen ...[more]

PMID: 9032293

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Project description:BACKGROUND: Theileria parva is a tick-borne protozoan parasite, which causes East Coast Fever, a disease of cattle in sub-Saharan Africa. Like Plasmodium falciparum, the parasite undergoes a transient diploid life-cycle stage in the gut of the arthropod vector, which involves an obligate sexual cycle. As assessed using low-resolution VNTR markers, the crossover (CO) rate in T. parva is relatively high and has been reported to vary across different regions of the genome; non-crossovers (NCOs) and CO-associated gene conversions have not yet been characterised due to the lack of informative markers. To examine all recombination events at high marker resolution, we sequenced the haploid genomes of two parental strains, and two recombinant clones derived from ticks fed on cattle that had been simultaneously co-infected with two different parasite isolates. RESULTS: By comparing the genome sequences, we were able to genotype over 64 thousand SNP markers with an average spacing of 127 bp in the two progeny clones. Previously unrecognized COs in sub-telomeric regions were detected. About 50% of CO breakpoints were accompanied by gene conversion events. Such a high fraction of COs accompanied by gene conversions demonstrated the contributions of meiotic recombination to the diversity and evolutionary success of T. parva, as the process not only redistributed existing genetic variations, but also altered allelic frequencies. Compared to COs, NCOs were more frequently observed and more uniformly distributed across the genome. In both progeny clones, genomic regions with more SNP markers had a reduced frequency of COs or NCOs, suggesting that the sequence divergence between the parental strains was high enough to adversely affect recombination frequencies. Intra-species polymorphism analysis identified 81 loci as likely to be under selection in the sequenced genomes. CONCLUSIONS: Using whole genome sequencing of two recombinant clones and their parents, we generated maps of COs, NCOs, and CO-associated gene conversion events for T. parva. The data comprises one of the highest-resolution genome-wide analyses of the multiple outcomes of meiotic recombination for this pathogen. The study also demonstrates the usefulness of high throughput sequencing typing for detailed analysis of recombination in organisms in which conventional genetic analysis is technically difficult.

Project description:An infection and treatment protocol is used to vaccinate cattle against Theileria parva infection. Due to incomplete cross-protection between different parasite isolates, a mixture of three isolates, termed the Muguga cocktail, is used for vaccination. While vaccination of cattle in some regions provides high levels of protection, some animals are not protected against challenge with buffalo-derived T. parva. Knowledge of the genetic composition of the Muguga cocktail vaccine is required to understand how vaccination is able to protect against field challenge and to identify the potential limitations of the vaccine. The aim of the current study was to determine the extent of genetic and antigenic diversity within the parasite isolates that constitute the Muguga cocktail. High throughput multi-locus sequencing of antigen-encoding loci was performed in parallel with typing using a panel of micro- and mini-satellite loci. The former focused on genes encoding CD8(+) T cell antigens, believed to be relevant to protective immunity. The results demonstrate that each of the three component stocks of the cocktail contains limited parasite genotypic diversity, with single alleles detected at many gene/satellite loci and, moreover, that two of the components show a very high level of similarity. Thus, the vaccine incorporates very little of the genetic and antigenic diversity observed in field populations of T. parva. The presence of alleles at low frequency (<10%) within vaccine component populations also points to the possibility of variability in the content of vaccine doses and the potential for loss of allelic diversity during tick passage. The results demonstrate that there is scope to modify the content of the vaccine in order to enhance its diversity and thus its potential for providing broad protection. The ability to accurately quantify genetic diversity in vaccine component stocks will facilitate improved quality control procedures designed to ensure the long-term efficacy of the vaccine.

Project description:BackgroundParasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species.ResultsIntergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know regulatory motifs in other species. These results suggest that these two motifs are likely to represent transcription factor binding sites in Theileria.ConclusionTheileria genomes are highly compact, with selection seemingly favoring short introns and intergenic regions. Three over-represented sequence motifs were independently identified in intergenic regions of both Theileria species, and the evidence suggests that at least two of them play a role in transcriptional control in T. parva. These are prime candidates for experimental validation of transcription factor binding sites in this single-celled eukaryotic parasite. Sequences similar to two of these Theileria motifs are conserved in Plasmodium hinting at the possibility of common regulatory machinery across the phylum Apicomplexa.

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Concerted evolution at a multicopy locus in the protozoan parasite Theileria parva: extreme divergence of potential protein-coding sequences.

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Concerted evolution at a multicopy locus in the protozoan parasite Theileria parva: extreme divergence of potential protein-coding sequences.

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