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Comparative genome analysis of Mycoplasma pneumoniae.

Xiao L, Ptacek T, Osborne JD, Crabb DM, Simmons WL, Lefkowitz EJ, Waites KB, Atkinson TP, Dybvig K - BMC Genomics (2015)

Bottom Line: Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed.The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex.Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA. lixiao@uab.edu.

ABSTRACT

Background: Mycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40% of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England.

Results: Illumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99% identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.

Conclusions: These data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer.

No MeSH data available.


Related in: MedlinePlus

Multiple protein sequence alignments showing strain-specific differences in P1 and ORF6. Type1 and 2 strain names are highlighted in blue and green, respectively. a A poly-serine repeat in P1 with varying lengths in various strains. 19294 has a uniquely long allele of the poly-serine repeat, and the repeat-length in the other strains does not strictly correspond to strain type. b A stop-loss mutation in MAC results in an additional 7 amino acids added to the protein sequence. c A pair of frameshifts results in the truncation of the beginning of ORF6 in MAC. Type1 and Type2 are representative sequences for type 1 and other type 2 strains, respectively. The new protein is predicted to use an alternate start codon by RAST: the starting methionine in MAC is the same codon as that which codes for the leucine in other type 1 and type 2 strains
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Fig5: Multiple protein sequence alignments showing strain-specific differences in P1 and ORF6. Type1 and 2 strain names are highlighted in blue and green, respectively. a A poly-serine repeat in P1 with varying lengths in various strains. 19294 has a uniquely long allele of the poly-serine repeat, and the repeat-length in the other strains does not strictly correspond to strain type. b A stop-loss mutation in MAC results in an additional 7 amino acids added to the protein sequence. c A pair of frameshifts results in the truncation of the beginning of ORF6 in MAC. Type1 and Type2 are representative sequences for type 1 and other type 2 strains, respectively. The new protein is predicted to use an alternate start codon by RAST: the starting methionine in MAC is the same codon as that which codes for the leucine in other type 1 and type 2 strains

Mentions: The two adjacent genes P1 and ORF6 code for critical components of the M. pneumoniae adhesin complex. These genes are within the largest region of sequence polymorphism between type 1 and type 2 strains (Fig. 1) and are the top two named genes by non-synonymous SNP count. To examine the variance in these genes further, the protein sequences were aligned and found to have identical amino acid sequences for most of their length. However, for both P1 and ORF6, there was one region where type 1 and type 2 strains had virtually no sequence identity. The alignments for the regions of high variation are shown in Fig. 4. Other variants found in these genes not in the large region of variation are listed in Additional file 3: Table S3 and Additional file 4: Table S4. Most of these other variants, like the sequence of the large regions of variation, are subtype specific, rather than strain specific. However, there were also some unique, strain specific variations with potentially significant effects in both P1 and ORF6 (Fig. 5). One of these was a variation in the number of AGT trinucleotide repeats coding for serine in a region between the repetitive elements RepMP4 and RepMP2/3 [48] within the P1 gene. The number of serine repeats ranged from 5–17 with strain 19294 bearing the longest (Fig. 5a).Fig. 4


Comparative genome analysis of Mycoplasma pneumoniae.

Xiao L, Ptacek T, Osborne JD, Crabb DM, Simmons WL, Lefkowitz EJ, Waites KB, Atkinson TP, Dybvig K - BMC Genomics (2015)

Multiple protein sequence alignments showing strain-specific differences in P1 and ORF6. Type1 and 2 strain names are highlighted in blue and green, respectively. a A poly-serine repeat in P1 with varying lengths in various strains. 19294 has a uniquely long allele of the poly-serine repeat, and the repeat-length in the other strains does not strictly correspond to strain type. b A stop-loss mutation in MAC results in an additional 7 amino acids added to the protein sequence. c A pair of frameshifts results in the truncation of the beginning of ORF6 in MAC. Type1 and Type2 are representative sequences for type 1 and other type 2 strains, respectively. The new protein is predicted to use an alternate start codon by RAST: the starting methionine in MAC is the same codon as that which codes for the leucine in other type 1 and type 2 strains
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537597&req=5

Fig5: Multiple protein sequence alignments showing strain-specific differences in P1 and ORF6. Type1 and 2 strain names are highlighted in blue and green, respectively. a A poly-serine repeat in P1 with varying lengths in various strains. 19294 has a uniquely long allele of the poly-serine repeat, and the repeat-length in the other strains does not strictly correspond to strain type. b A stop-loss mutation in MAC results in an additional 7 amino acids added to the protein sequence. c A pair of frameshifts results in the truncation of the beginning of ORF6 in MAC. Type1 and Type2 are representative sequences for type 1 and other type 2 strains, respectively. The new protein is predicted to use an alternate start codon by RAST: the starting methionine in MAC is the same codon as that which codes for the leucine in other type 1 and type 2 strains
Mentions: The two adjacent genes P1 and ORF6 code for critical components of the M. pneumoniae adhesin complex. These genes are within the largest region of sequence polymorphism between type 1 and type 2 strains (Fig. 1) and are the top two named genes by non-synonymous SNP count. To examine the variance in these genes further, the protein sequences were aligned and found to have identical amino acid sequences for most of their length. However, for both P1 and ORF6, there was one region where type 1 and type 2 strains had virtually no sequence identity. The alignments for the regions of high variation are shown in Fig. 4. Other variants found in these genes not in the large region of variation are listed in Additional file 3: Table S3 and Additional file 4: Table S4. Most of these other variants, like the sequence of the large regions of variation, are subtype specific, rather than strain specific. However, there were also some unique, strain specific variations with potentially significant effects in both P1 and ORF6 (Fig. 5). One of these was a variation in the number of AGT trinucleotide repeats coding for serine in a region between the repetitive elements RepMP4 and RepMP2/3 [48] within the P1 gene. The number of serine repeats ranged from 5–17 with strain 19294 bearing the longest (Fig. 5a).Fig. 4

Bottom Line: Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed.The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex.Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, 35294, USA. lixiao@uab.edu.

ABSTRACT

Background: Mycoplasma pneumoniae is a common pathogen that causes upper and lower respiratory tract infections in people of all ages, responsible for up to 40% of community-acquired pneumonias. It also causes a wide array of extrapulmonary infections and autoimmune phenomena. Phylogenetic studies of the organism have been generally restricted to specific genes or regions of the genome, because whole genome sequencing has been completed for only 4 strains. To better understand the physiology and pathogenicity of this important human pathogen, we performed comparative genomic analysis of 15 strains of M. pneumoniae that were isolated between the 1940s to 2009 from respiratory specimens and cerebrospinal fluid originating from the USA, China and England.

Results: Illumina MiSeq whole genome sequencing was performed on the 15 strains and all genome sequences were completed. Results from the comparative genomic analysis indicate that although about 1500 SNP and indel variants exist between type1 and type 2 strains, there is an overall high degree of sequence similarity among the strains (>99% identical to each other). Within the two subtypes, conservation of most genes, including the CARDS toxin gene and arginine deiminase genes, was observed. The major variation occurs in the P1 and ORF6 genes associated with the adhesin complex. Multiple hsdS genes (encodes S subunit of type I restriction enzyme) with variable tandem repeat copy numbers were found in all 15 genomes.

Conclusions: These data indicate that despite conclusions drawn from 16S rRNA sequences suggesting rapid evolution, the M. pneumoniae genome is extraordinarily stable over time and geographic distance across the globe with a striking lack of evidence of horizontal gene transfer.

No MeSH data available.


Related in: MedlinePlus