Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.
Comparative analysis of Mycobacterium tuberculosis pe and ppe genes reveals high sequence variation and an apparent absence of selective constraints.
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DOI：
10.1371/journal.pone.0030593
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Gey van Pittius NC
中科院分区：
文献类型：
--
作者：
McEvoy CR;Cloete R;Müller B;Schürch AC;van Helden PD;Gagneux S;Warren RM;Gey van Pittius NC
结核分枝杆菌复合体（MTBC）基因组包含两个大的基因家族，称为pe和ppe。pe/ppe蛋白的功能仍然是谜，但研究表明它们是分泌的或与细胞表面相关的，并参与细菌的毒力。先前的研究也表明，一些pe/ppe基因是多态的，这一发现表明与抗原变异有关。利用18个公开的MTBC全基因组序列的比较序列分析，我们对33个pe（不包括pe_pgrs）和66个ppe基因进行了比对，以检测遗传变异的频率和性质。这项工作还得到了覆盖结核分枝杆菌系统发育树所有主要谱系的40个不同且定义明确的临床分离株的14个pe/ppe（包括5个pe_pgrs）基因全基因测序的补充。我们发现，pe（不包括pgrs）和ppe基因中的nsSNP分别比非pe/ppe基因高3.0和3.3倍，并且许多其他突变类型也以高频率存在。以前的研究表明，非pe/ppe结核分枝杆菌基因表现出非常低的纯化选择水平。在这里，我们还表明，与这些基因相比，pe/ppe家族的选择压力进一步减少，这表明中性进化。这与“经典”抗原性变异的正选择压力不一致。最后，通过分析如此大量的基因，我们能够检测到个体基因和基因亚家族之间突变类型和频率的巨大差异。高变化率和缺乏选择性约束为潜在的pe/ppe功能提供了有价值的见解。由于pe/ppe蛋白具有高度的抗原性，并已作为潜在的疫苗成分进行了研究，这些结果也应证明对结核分枝杆菌疫苗设计方面具有参考价值。
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.
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影响因子：
3
作者：
Bonanni, D;Rindi, L;Garzelli, C
通讯作者：
Garzelli, C
DOI：
10.1099/00221287-145-12-3487
发表时间：
1999-12-01
期刊：
MICROBIOLOGY-UK
影响因子：
--
作者：
Espitia, C;Laclette, JP;Moreno, C
通讯作者：
Moreno, C
影响因子：
5.5
作者：
Chaitra, MG;Hariharaputran, S;Nayak, R
通讯作者：
Nayak, R
影响因子：
3.5
作者：
Flores, J;Espitia, C
通讯作者：
Espitia, C
影响因子：
3.7
作者：
Comas I;Homolka S;Niemann S;Gagneux S
通讯作者：
Gagneux S