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Complete mitochondrial genome sequence of three Tetrahymena species reveals mutation hot spots and accelerated nonsynonymous substitutions in Ymf genes.

Moradian MM, Beglaryan D, Skozylas JM, Kerikorian V - PLoS ONE (2007)

Bottom Line: We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these approximately 47 kb long linear genomes.Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes.Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California, United States of America. mmoradia@ucla.edu

ABSTRACT
The ciliate Tetrahymena, a model organism, contains divergent mitochondrial (Mt) genome with unusual properties, where half of its 44 genes still remain without a definitive function. These genes could be categorized into two major groups of KPC (known protein coding) and Ymf (genes without an identified function). To gain insights into the mechanisms underlying gene divergence and molecular evolution of Tetrahymena (T.) Mt genomes, we sequenced three Mt genomes of T.paravorax, T.pigmentosa, and T.malaccensis. These genomes were aligned and the analyses were carried out using several programs that calculate distance, nucleotide substitution (dn/ds), and their rate ratios (omega) on individual codon sites and via a sliding window approach. Comparative genomic analysis indicated a conserved putative transcription control sequence, a GC box, in a region where presumably transcription and replication initiate. We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these approximately 47 kb long linear genomes. Another significant finding was the presence of at least one or more highly variable regions in Ymf genes where majority of substitutions were concentrated. These regions were mutation hotspots where elevated distances and the dn/ds ratios were primarily due to an increase in the number of nonsynonymous substitutions, suggesting relaxed selective constraint. However, in a few Ymf genes, accelerated rates of nonsynonymous substitutions may be due to positive selection. Similarly, on protein level the majority of amino acid replacements occurred in these regions. Ymf genes comprise half of the genes in Tetrahymena Mt genomes, so understanding why they have not been assigned definitive functions is an important aspect of molecular evolution. Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes. Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions.

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Relationship between dn/ds ratios, dn, and ds values for Ymf genes.Values for each point are from 10 possible pairwise comparisons of five Tetrahymena species. For simplicity the values from pairwise comparison between T.thermophila and T.pyriformis are shown. They are from average window of size 180 sliding 30 nucleotides per permutation.
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pone-0000650-g004: Relationship between dn/ds ratios, dn, and ds values for Ymf genes.Values for each point are from 10 possible pairwise comparisons of five Tetrahymena species. For simplicity the values from pairwise comparison between T.thermophila and T.pyriformis are shown. They are from average window of size 180 sliding 30 nucleotides per permutation.

Mentions: To investigate how nucleotide and amino acid replacement types correlated during the evolution of the Tetrahymena Mt genes we compared the dn/ds ratios using the entire sequence for each gene. Pairwise comparisons indicated that Ymf genes on average accumulated more nonsynonymous substitutions resulting in almost three times higher dn/ds ratios than KPC genes (0.48 vs. 0.17). None of the Ymfs had an average dn/ds>1, therefore we suspended the possibility of positive selection pending further analysis. Thus to analyze the main reasons for higher dn/ds values in Ymf genes we introduced a sliding window software program, which calculated nucleotide substitutions as distances and dn/ds ratios for each window. We confirmed our analysis with an alternative program called SWAPSC (see material and methods). These programs completed the tasks by showing the relationships between dn, ds, and their ratio. This relationship was quite clear for KPC genes where they had very low dn and much higher ds values resulting in low dn/ds ratios (Figure 3). Conversely the Ymf genes contained regions with elevated numbers of nonsynonymous substitutions resulting in higher dn/ds ratios. These regions, which were present in almost all of the Ymf genes and in small regions of a few KPC genes such as Nad5, Cox2, and Rps3, could be considered as mutation hotspots. An illustration of these hotspots in Ymf genes is shown in figure 4, where they were compared to other regions of the Ymf genes to show that dn/ds ratios in these genes ranged from almost zero to over 1.5. On the other hand, the conserved regions of Ymf genes had dn/ds ratios comparable to that of KPC genes, which could potentially represent the functional domains of their protein products.


Complete mitochondrial genome sequence of three Tetrahymena species reveals mutation hot spots and accelerated nonsynonymous substitutions in Ymf genes.

Moradian MM, Beglaryan D, Skozylas JM, Kerikorian V - PLoS ONE (2007)

Relationship between dn/ds ratios, dn, and ds values for Ymf genes.Values for each point are from 10 possible pairwise comparisons of five Tetrahymena species. For simplicity the values from pairwise comparison between T.thermophila and T.pyriformis are shown. They are from average window of size 180 sliding 30 nucleotides per permutation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1919467&req=5

pone-0000650-g004: Relationship between dn/ds ratios, dn, and ds values for Ymf genes.Values for each point are from 10 possible pairwise comparisons of five Tetrahymena species. For simplicity the values from pairwise comparison between T.thermophila and T.pyriformis are shown. They are from average window of size 180 sliding 30 nucleotides per permutation.
Mentions: To investigate how nucleotide and amino acid replacement types correlated during the evolution of the Tetrahymena Mt genes we compared the dn/ds ratios using the entire sequence for each gene. Pairwise comparisons indicated that Ymf genes on average accumulated more nonsynonymous substitutions resulting in almost three times higher dn/ds ratios than KPC genes (0.48 vs. 0.17). None of the Ymfs had an average dn/ds>1, therefore we suspended the possibility of positive selection pending further analysis. Thus to analyze the main reasons for higher dn/ds values in Ymf genes we introduced a sliding window software program, which calculated nucleotide substitutions as distances and dn/ds ratios for each window. We confirmed our analysis with an alternative program called SWAPSC (see material and methods). These programs completed the tasks by showing the relationships between dn, ds, and their ratio. This relationship was quite clear for KPC genes where they had very low dn and much higher ds values resulting in low dn/ds ratios (Figure 3). Conversely the Ymf genes contained regions with elevated numbers of nonsynonymous substitutions resulting in higher dn/ds ratios. These regions, which were present in almost all of the Ymf genes and in small regions of a few KPC genes such as Nad5, Cox2, and Rps3, could be considered as mutation hotspots. An illustration of these hotspots in Ymf genes is shown in figure 4, where they were compared to other regions of the Ymf genes to show that dn/ds ratios in these genes ranged from almost zero to over 1.5. On the other hand, the conserved regions of Ymf genes had dn/ds ratios comparable to that of KPC genes, which could potentially represent the functional domains of their protein products.

Bottom Line: We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these approximately 47 kb long linear genomes.Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes.Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions.

View Article: PubMed Central - PubMed

Affiliation: Department of Ecology and Evolutionary Biology, University of California Los Angeles, Los Angeles, California, United States of America. mmoradia@ucla.edu

ABSTRACT
The ciliate Tetrahymena, a model organism, contains divergent mitochondrial (Mt) genome with unusual properties, where half of its 44 genes still remain without a definitive function. These genes could be categorized into two major groups of KPC (known protein coding) and Ymf (genes without an identified function). To gain insights into the mechanisms underlying gene divergence and molecular evolution of Tetrahymena (T.) Mt genomes, we sequenced three Mt genomes of T.paravorax, T.pigmentosa, and T.malaccensis. These genomes were aligned and the analyses were carried out using several programs that calculate distance, nucleotide substitution (dn/ds), and their rate ratios (omega) on individual codon sites and via a sliding window approach. Comparative genomic analysis indicated a conserved putative transcription control sequence, a GC box, in a region where presumably transcription and replication initiate. We also found distinct features in Mt genome of T.paravorax despite similar genome organization among these approximately 47 kb long linear genomes. Another significant finding was the presence of at least one or more highly variable regions in Ymf genes where majority of substitutions were concentrated. These regions were mutation hotspots where elevated distances and the dn/ds ratios were primarily due to an increase in the number of nonsynonymous substitutions, suggesting relaxed selective constraint. However, in a few Ymf genes, accelerated rates of nonsynonymous substitutions may be due to positive selection. Similarly, on protein level the majority of amino acid replacements occurred in these regions. Ymf genes comprise half of the genes in Tetrahymena Mt genomes, so understanding why they have not been assigned definitive functions is an important aspect of molecular evolution. Importantly, nucleotide substitution types and rates suggest possible reasons for not being able to find homologues for Ymf genes. Additionally, comparative genomic analysis of complete Mt genomes is essential in identifying biologically significant motifs such as control regions.

Show MeSH
Related in: MedlinePlus