Identification of positively selected genes in human pathogenic
treponemes: Syphilis-, yaws-, and bejel-causing strains differ
in sets of genes showing adaptive evolution

J 2019

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

MADERANKOVA, Denisa, Lenka MIKALOVÁ, Michal STROUHAL, Simon VADJAK, Ivana KUKLOVA et. al.

Basic information

Original name

Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution

Authors

MADERANKOVA, Denisa (203 Czech Republic), Lenka MIKALOVÁ (203 Czech Republic, belonging to the institution), Michal STROUHAL (203 Czech Republic, belonging to the institution), Simon VADJAK (203 Czech Republic), Ivana KUKLOVA (203 Czech Republic), Petra POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Lenka KRBKOVÁ (203 Czech Republic, belonging to the institution), Pavlina KOSCOVA (203 Czech Republic), Ivo PROVAZNIK (203 Czech Republic) and David ŠMAJS (203 Czech Republic, guarantor, belonging to the institution)

Edition

PLoS neglected tropical diseases, San Francisco, Public Library of Science, 2019, 1935-2735

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30303 Infectious Diseases

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.885

RIV identification code

RIV/00216224:14110/19:00108016

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1371/journal.pntd.0007463

UT WoS

000473779100047

Keywords in English

COMPLETE GENOME SEQUENCE; PALLIDUM SUBSP PALLIDUM; CODON-SUBSTITUTION MODELS; NUCLEOTIDE SUBSTITUTIONS; PHYLOGENETIC ANALYSIS; MOLECULAR ADAPTATION; MAXIMUM-LIKELIHOOD; TPRK; RECOMBINATION; DIAGNOSTICS

Abstract

V originále

Background Pathogenic treponemes related to Treponema pallidum are both human (causing syphilis, yaws, bejel) and animal pathogens (infections of primates, venereal spirochetosis in rabbits). A set of 11 treponemal genome sequences including those of five Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14, Chicago), four T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), one T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPeC) were tested for the presence of positively selected genes. Methodology/Principal findings A total of 1068 orthologous genes annotated in all 11 genomes were tested for the presence of positively selected genes using both site and branch-site models with CODEML (PAML package). Subsequent analyses with sequences obtained from 62 treponemal draft genomes were used for the identification of positively selected amino acid positions. Synthetic biotinylated peptides were designed to cover positively selected protein regions and these peptides were tested for reactivity with the patient's syphilis sera. Altogether, 22 positively selected genes were identified in the TP genomes and TPA sets of positively selected genes differed from TPE genes. While genetic variability among TPA strains was predominantly present in a number of genetic loci, genetic variability within TPE and TEN strains was distributed more equally along the chromosome. Several syphilitic sera were shown to react with some peptides derived from the protein sequences evolving under positive selection. Conclusions/Significance The syphilis-, yaws-, and bejel-causing strains differed relative to sets of positively selected genes. Most of the positively selected chromosomal loci were identified among the TPA treponemes. The local accumulation of genetic variability suggests that the diversification of TPA strains took place predominantly in a limited number of genomic regions compared to the more dispersed genetic diversity differentiating TPE and TEN strains. The identification of positively selected sites in tpr genes and genes encoding outer membrane proteins suggests their role during infection of human and animal hosts. The driving force for adaptive evolution at these loci thus appears to be the host immune response as supported by observed reactivity of syphilitic sera with some peptides derived from protein sequences showing adaptive evolution. Author summary In the genus Treponema there are several human and animal pathogens that include the causative agent of syphilis (Treponema pallidum ssp. pallidum; TPA), the causative agent of yaws (T. p. ssp. pertenue; TPE), and the causative agent of endemic syphilis (T. p. ssp. endemicum; TEN). T. paraluisleporidarum causes venereal spirochetosis in rabbits. We used whole genome sequences of 11 treponemal strains together with additional 62 draft genomic data to identify genes evolving under positive selection. The identified genes evolving under positive selection partly overlapped with the genes previously reported as recombinant and were found to be different in treponemal subspecies. Since both genetic recombination and positive selection could allow a survival of pathogenic bacteria despite the human immune response, identification of such genes could predict the major antigens recognized by the human immune system and also identify the most suitable components for development of an anti-treponemal vaccine.

Links

GA17-25455S, research and development project

Name: Studium genomů patogenních treponem na základě analýzy jednotlivých buněk

Investor: Czech Science Foundation

GC18-23521J, research and development project

Name: Treponematózy u zástupců řádu zajícovci: genetická diverzita treponem a příbuznost s lidským patogenem T. pallidum

Investor: Czech Science Foundation

GP14-29596P, research and development project

Name: Genomová variabilita treponem během experimentální infekce

Investor: Czech Science Foundation

MUNI/A/1087/2018, interní kód MU

Name: Molekulární a buněčná biologie pro biomedicínské vědy

Investor: Masaryk University, Category A

Citovat

MADERANKOVA, Denisa, Lenka MIKALOVÁ, Michal STROUHAL, Simon VADJAK, Ivana KUKLOVA, Petra POSPÍŠILOVÁ, Lenka KRBKOVÁ, Pavlina KOSCOVA, Ivo PROVAZNIK and David ŠMAJS. Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution. PLoS neglected tropical diseases. San Francisco: Public Library of Science, 2019, vol. 13, No 6, p. 1-18. ISSN 1935-2735. Available from: https://dx.doi.org/10.1371/journal.pntd.0007463.

@article{1603777,
   author = {Maderankova, Denisa and Mikalová, Lenka and Strouhal, Michal and Vadjak, Simon and Kuklova, Ivana and Pospíšilová, Petra and Krbková, Lenka and Koscova, Pavlina and Provaznik, Ivo and Šmajs, David},
   article_location = {San Francisco},
   article_number = {6},
   doi = {http://dx.doi.org/10.1371/journal.pntd.0007463},
   keywords = {COMPLETE GENOME SEQUENCE; PALLIDUM SUBSP PALLIDUM; CODON-SUBSTITUTION MODELS; NUCLEOTIDE SUBSTITUTIONS; PHYLOGENETIC ANALYSIS; MOLECULAR ADAPTATION; MAXIMUM-LIKELIHOOD; TPRK; RECOMBINATION; DIAGNOSTICS},
   language = {eng},
   issn = {1935-2735},
   journal = {PLoS neglected tropical diseases},
   title = {Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution},
   url = {http://dx.doi.org/10.1371/journal.pntd.0007463},
   volume = {13},
   year = {2019}
}

TY  - JOUR
ID  - 1603777
AU  - Maderankova, Denisa - Mikalová, Lenka - Strouhal, Michal - Vadjak, Simon - Kuklova, Ivana - Pospíšilová, Petra - Krbková, Lenka - Koscova, Pavlina - Provaznik, Ivo - Šmajs, David
PY  - 2019
TI  - Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution
JF  - PLoS neglected tropical diseases
VL  - 13
IS  - 6
SP  - 1-18
EP  - 1-18
PB  - Public Library of Science
SN  - 19352735
KW  - COMPLETE GENOME SEQUENCE
KW  - PALLIDUM SUBSP PALLIDUM
KW  - CODON-SUBSTITUTION MODELS
KW  - NUCLEOTIDE SUBSTITUTIONS
KW  - PHYLOGENETIC ANALYSIS
KW  - MOLECULAR ADAPTATION
KW  - MAXIMUM-LIKELIHOOD
KW  - TPRK
KW  - RECOMBINATION
KW  - DIAGNOSTICS
UR  - http://dx.doi.org/10.1371/journal.pntd.0007463
L2  - http://dx.doi.org/10.1371/journal.pntd.0007463
N2  - Background Pathogenic treponemes related to Treponema pallidum are both human (causing syphilis, yaws, bejel) and animal pathogens (infections of primates, venereal spirochetosis in rabbits). A set of 11 treponemal genome sequences including those of five Treponema pallidum ssp. pallidum (TPA) strains (Nichols, DAL-1, Mexico A, SS14, Chicago), four T. p. ssp. pertenue (TPE) strains (CDC-2, Gauthier, Samoa D, Fribourg-Blanc), one T. p. ssp. endemicum (TEN) strain (Bosnia A) and one strain (Cuniculi A) of Treponema paraluisleporidarum ecovar Cuniculus (TPeC) were tested for the presence of positively selected genes. Methodology/Principal findings A total of 1068 orthologous genes annotated in all 11 genomes were tested for the presence of positively selected genes using both site and branch-site models with CODEML (PAML package). Subsequent analyses with sequences obtained from 62 treponemal draft genomes were used for the identification of positively selected amino acid positions. Synthetic biotinylated peptides were designed to cover positively selected protein regions and these peptides were tested for reactivity with the patient's syphilis sera. Altogether, 22 positively selected genes were identified in the TP genomes and TPA sets of positively selected genes differed from TPE genes. While genetic variability among TPA strains was predominantly present in a number of genetic loci, genetic variability within TPE and TEN strains was distributed more equally along the chromosome. Several syphilitic sera were shown to react with some peptides derived from the protein sequences evolving under positive selection. Conclusions/Significance The syphilis-, yaws-, and bejel-causing strains differed relative to sets of positively selected genes. Most of the positively selected chromosomal loci were identified among the TPA treponemes. The local accumulation of genetic variability suggests that the diversification of TPA strains took place predominantly in a limited number of genomic regions compared to the more dispersed genetic diversity differentiating TPE and TEN strains. The identification of positively selected sites in tpr genes and genes encoding outer membrane proteins suggests their role during infection of human and animal hosts. The driving force for adaptive evolution at these loci thus appears to be the host immune response as supported by observed reactivity of syphilitic sera with some peptides derived from protein sequences showing adaptive evolution. Author summary In the genus Treponema there are several human and animal pathogens that include the causative agent of syphilis (Treponema pallidum ssp. pallidum; TPA), the causative agent of yaws (T. p. ssp. pertenue; TPE), and the causative agent of endemic syphilis (T. p. ssp. endemicum; TEN). T. paraluisleporidarum causes venereal spirochetosis in rabbits. We used whole genome sequences of 11 treponemal strains together with additional 62 draft genomic data to identify genes evolving under positive selection. The identified genes evolving under positive selection partly overlapped with the genes previously reported as recombinant and were found to be different in treponemal subspecies. Since both genetic recombination and positive selection could allow a survival of pathogenic bacteria despite the human immune response, identification of such genes could predict the major antigens recognized by the human immune system and also identify the most suitable components for development of an anti-treponemal vaccine.
ER  -

MADERANKOVA, Denisa, Lenka MIKALOVÁ, Michal STROUHAL, Simon VADJAK, Ivana KUKLOVA, Petra POSPÍŠILOVÁ, Lenka KRBKOVÁ, Pavlina KOSCOVA, Ivo PROVAZNIK and David ŠMAJS. Identification of positively selected genes in human pathogenic treponemes: Syphilis-, yaws-, and bejel-causing strains differ in sets of genes showing adaptive evolution. \textit{PLoS neglected tropical diseases}. San Francisco: Public Library of Science, 2019, vol.~13, No~6, p.~1-18. ISSN~1935-2735. Available from: https://dx.doi.org/10.1371/journal.pntd.0007463.

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