NDLI: Comparative Analysis of Mycobacterium tuberculosis pe and ppe Genes Reveals High Sequence Variation and an Apparent Absence of Selective Constraints

Content Provider	PubMed Central
Author	Mcevoy, Christopher R. E. Cloete, Ruben Müller, Borna Schürch, Anita C. Helden, Paul D. Van Gagneux, Sebastien Warren, Robin M. Gey, Van Pittius Nicolaas C.
Editor	Olivier, Neyrolles
Copyright Year	2012
Abstract	Mycobacterium tuberculosis complex (MTBC) genomes contain 2 large gene families termed pe and ppe. The function of pe/ppe proteins remains enigmatic but studies suggest that they are secreted or cell surface associated and are involved in bacterial virulence. Previous studies have also shown that some pe/ppe genes are polymorphic, a finding that suggests involvement in antigenic variation. Using comparative sequence analysis of 18 publicly available MTBC whole genome sequences, we have performed alignments of 33 pe (excluding pe_pgrs) and 66 ppe genes in order to detect the frequency and nature of genetic variation. This work has been supplemented by whole gene sequencing of 14 pe/ppe (including 5 pe_pgrs) genes in a cohort of 40 diverse and well defined clinical isolates covering all the main lineages of the M. tuberculosis phylogenetic tree. We show that nsSNP's in pe (excluding pgrs) and ppe genes are 3.0 and 3.3 times higher than in non-pe/ppe genes respectively and that numerous other mutation types are also present at a high frequency. It has previously been shown that non-pe/ppe M. tuberculosis genes display a remarkably low level of purifying selection. Here, we also show that compared to these genes those of the pe/ppe families show a further reduction of selection pressure that suggests neutral evolution. This is inconsistent with the positive selection pressure of “classical” antigenic variation. Finally, by analyzing such a large number of genes we were able to detect large differences in mutation type and frequency between both individual genes and gene sub-families. The high variation rates and absence of selective constraints provides valuable insights into potential pe/ppe function. Since pe/ppe proteins are highly antigenic and have been studied as potential vaccine components these results should also prove informative for aspects of M. tuberculosis vaccine design.
Related Links	http://dx.doi.org/10.1371/journal.pone.0030593
Starting Page	30593
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	4
Volume Number	7
Language	English
Publisher	Public Library of Science
Publisher Date	2012-04-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Sequence analysis corresponding to the PPE and PE proteins inMycobacterium tuberculosis and other genomes

The PE-PPE Domain in Mycobacterium Reveals a Serine α/β Hydrolase Fold and Function: An In-Silico Analysis

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

Studies on the functional role of unusual PE PPE gene clusters in the pathogenesis of Mycobacterium tuberculosis

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing

Modulation of the Activity of Mycobacterium tuberculosis LipY by Its PE Domain

A complete high quality nanopore-only assembly of an XDR Mycobacterium tuberculosis Beijing lineage strain identifies novel variation in repetitive PE/PPE gene regions

Structure of a PE–PPE–EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion

Comparative Analysis of Mycobacterium tuberculosis pe and ppe Genes Reveals High Sequence Variation and an Apparent Absence of Selective Constraints

Similar Documents

Sequence analysis corresponding to the PPE and PE proteins inMycobacterium tuberculosis and other genomes

The PE-PPE Domain in Mycobacterium Reveals a Serine α/β Hydrolase Fold and Function: An In-Silico Analysis

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

Recombination in pe/ppe genes contributes to genetic variation in Mycobacterium tuberculosis lineages

Studies on the functional role of unusual PE PPE gene clusters in the pathogenesis of Mycobacterium tuberculosis

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing

Modulation of the Activity of Mycobacterium tuberculosis LipY by Its PE Domain

A complete high quality nanopore-only assembly of an XDR Mycobacterium tuberculosis Beijing lineage strain identifies novel variation in repetitive PE/PPE gene regions

Structure of a PE–PPE–EspG complex from Mycobacterium tuberculosis reveals molecular specificity of ESX protein secretion

Comparative Analysis of Mycobacterium tuberculosis pe and ppe Genes Reveals High Sequence Variation and an Apparent Absence of Selective Constraints