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Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families.

Morelli G, Didelot X, Kusecek B, Schwarz S, Bahlawane C, Falush D, Suerbaum S, Achtman M - PLoS Genet. (2010)

Bottom Line: The estimates indicate that the short-term mutation rate is 1.4 x 10(-6) (serial isolates) to 4.5 x 10(-6) (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation.The long-term mutation rate over millennia is 5-17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection.Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Max-Planck Institute for Infection Biology, Berlin, Germany.

ABSTRACT
Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4 x 10(-6) (serial isolates) to 4.5 x 10(-6) (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5-17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude.

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Related in: MedlinePlus

Sequence differences for 78 gene fragments (X axis) that were tested from 34 pairs of sequential isolates (Y axis).Of 2,650 pairs of sequenced gene fragments, 2,526 were identical (white), 62 differ by one polymorphism (green), 12 had two polymorphisms (red), and 50 had at least three (black). Two question marks indicate missing data that were not used for comparisons. Gene fragments are designated by their designations in the genome of 26695 (HPxxxx) [63], except that the first seven gene fragments that are used for MLST of H. pylori [34] also include the gene designations.
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pgen-1001036-g002: Sequence differences for 78 gene fragments (X axis) that were tested from 34 pairs of sequential isolates (Y axis).Of 2,650 pairs of sequenced gene fragments, 2,526 were identical (white), 62 differ by one polymorphism (green), 12 had two polymorphisms (red), and 50 had at least three (black). Two question marks indicate missing data that were not used for comparisons. Gene fragments are designated by their designations in the genome of 26695 (HPxxxx) [63], except that the first seven gene fragments that are used for MLST of H. pylori [34] also include the gene designations.

Mentions: Figure 2 shows a comparison of the paired sequences from the serial isolates. Out of a total of 2650 pair-wise sequence comparisons of gene fragments, 62 contained 1 polymorphic site, 12 showed two polymorphisms and 50 showed more than two polymorphisms. The total number of fragments with sequence differences correlates significantly with the time difference between the serial samples (R = 0.4, p = 0.02; Figure 3A), referred to as the minimal age below. Thus, sequence diversity introduced by mutation plus recombination seems to accumulate in a clock-like manner in infected individuals. We note that minimal age represents only a lower bound for the time of divergence between those isolates because the variant might have arisen earlier and persisted together with the parent in the form of a mixed infection. The maximal age is the extreme opposite scenario to the minimal age, namely that the variants evolved soon after birth. We approximated the maximal time of divergence within each individual as the sum of the ages at sampling. There is apparently no correlation between this maximal age and the number of polymorphic fragments (R = 0.07, p = 0.7, Figure 3B).


Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families.

Morelli G, Didelot X, Kusecek B, Schwarz S, Bahlawane C, Falush D, Suerbaum S, Achtman M - PLoS Genet. (2010)

Sequence differences for 78 gene fragments (X axis) that were tested from 34 pairs of sequential isolates (Y axis).Of 2,650 pairs of sequenced gene fragments, 2,526 were identical (white), 62 differ by one polymorphism (green), 12 had two polymorphisms (red), and 50 had at least three (black). Two question marks indicate missing data that were not used for comparisons. Gene fragments are designated by their designations in the genome of 26695 (HPxxxx) [63], except that the first seven gene fragments that are used for MLST of H. pylori [34] also include the gene designations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2908706&req=5

pgen-1001036-g002: Sequence differences for 78 gene fragments (X axis) that were tested from 34 pairs of sequential isolates (Y axis).Of 2,650 pairs of sequenced gene fragments, 2,526 were identical (white), 62 differ by one polymorphism (green), 12 had two polymorphisms (red), and 50 had at least three (black). Two question marks indicate missing data that were not used for comparisons. Gene fragments are designated by their designations in the genome of 26695 (HPxxxx) [63], except that the first seven gene fragments that are used for MLST of H. pylori [34] also include the gene designations.
Mentions: Figure 2 shows a comparison of the paired sequences from the serial isolates. Out of a total of 2650 pair-wise sequence comparisons of gene fragments, 62 contained 1 polymorphic site, 12 showed two polymorphisms and 50 showed more than two polymorphisms. The total number of fragments with sequence differences correlates significantly with the time difference between the serial samples (R = 0.4, p = 0.02; Figure 3A), referred to as the minimal age below. Thus, sequence diversity introduced by mutation plus recombination seems to accumulate in a clock-like manner in infected individuals. We note that minimal age represents only a lower bound for the time of divergence between those isolates because the variant might have arisen earlier and persisted together with the parent in the form of a mixed infection. The maximal age is the extreme opposite scenario to the minimal age, namely that the variants evolved soon after birth. We approximated the maximal time of divergence within each individual as the sum of the ages at sampling. There is apparently no correlation between this maximal age and the number of polymorphic fragments (R = 0.07, p = 0.7, Figure 3B).

Bottom Line: The estimates indicate that the short-term mutation rate is 1.4 x 10(-6) (serial isolates) to 4.5 x 10(-6) (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation.The long-term mutation rate over millennia is 5-17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection.Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology, Max-Planck Institute for Infection Biology, Berlin, Germany.

ABSTRACT
Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4 x 10(-6) (serial isolates) to 4.5 x 10(-6) (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5-17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude.

Show MeSH
Related in: MedlinePlus