Metagenomic signatures of balancing selection in the human gut.
Metagenomic signatures of balancing selection in the human gut.
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DOI：
10.1111/mec.16474
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发表时间：
2023-05
影响因子：
4.9
通讯作者：
Moeller, Andrew H.
中科院分区：
文献类型：
--
作者：
Moeller, Andrew H.
人类肠道菌群的细菌谱系与许多环境变量的时空波动作斗争，包括抗生素等极端选择性药物的发作。适应性景观的振荡可以对种群施加平衡选择，在功能重要的基因组位点的序列变化中留下特征特征。尽管它们对肠道细菌适应具有潜在的重要性，但平衡选择的宏基因组目标尚未确定。在这里，我提出了群体遗传证据，即平衡选择维持了多种优势肠道细菌物种的多药物外排泵的等位基因多样性。对来自287种细菌（118,617个宏基因组组装基因组）的566,958个基因进行了宏基因组扫描，结果表明大多数基因通过纯化选择被保守。然而，数十个核心开放阅读框（corf）显示出明显偏离其物种基因组背景的正Tajima’s D值，表明平衡选择的作用。多药外排泵（MEPs）在工业化人群（而非工业化人群）的田岛D值为bbb30的corf中显著富集。多氏拟杆菌MEP的AcrB亚基在所有CORF中表现出最高的Tajima's D。该CORF的不同单倍型显示出正向选择的证据，并与大肠杆菌AcrB亚基同源，该亚基结合四环素和大环内酯类抗生素，表明其功能意义，并暗示医用抗生素作为一种选择剂作用于该位点。其他被确定为平衡选择目标的蛋白质包括肽聚糖/LPS o -乙酰化酶和离子转运蛋白。有趣的是，基于宏基因组数据，作用于肠道细菌物种的平衡选择程度与肠道物种丰度相关，进一步表明所鉴定的等位基因变异对健康有益。
Bacterial lineages that populate the human gut microbiota contend with spatial and temporal fluctuations in numerous environmental variables, including bouts of extreme selective agents such as antibiotics. Oscillations in the adaptive landscape can impose balancing selection on populations, leaving characteristic signatures in the sequence variation of functionally significant genomic loci. Despite their potential importance for gut bacterial adaptation, the metagenomic targets of balancing selection have not been identified. Here, I present population genetic evidence that balancing selection maintains allelic diversity in multidrug efflux pumps of multiple predominant gut bacterial species. Metagenome-wide scans of 566,958 genes from 287 bacterial species represented by 118,617 metagenome-assembled genomes indicated that most genes have been conserved by purifying selection. However, dozens of core open reading frames (CORFs) displayed positive Tajima's D values that deviated significantly from their species’ genomic backgrounds, indicating the action of balancing selection. Multidrug efflux pumps (MEPs) from a diversity of bacterial species were significantly enriched among the CORFs with Tajima's D values >3 in industrialized, but not nonindustrialized, human populations. The AcrB subunit of an MEP from Bacteroides dorei displayed the highest Tajima's D of any CORF. Divergent haplotypes of this CORF displayed evidence of positive selection and homology to an Escherichia coli AcrB subunit that binds tetracycline and macrolide antibiotics, suggesting functional significance and implicating medical antibiotics as an agent of selection acting on this locus. Other proteins identified as targets of balancing selection included peptidoglycan/LPS O-acetylases and ion transporters. Intriguingly, the degree of balancing selection acting on gut bacterial species was associated with species abundance in the gut based on metagenomic data, further suggesting fitness benefits of the allelic variation identified.
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影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
影响因子：
6.6
作者：
Revell, Liam J.
通讯作者：
Revell, Liam J.
影响因子：
14.9
作者：
Burley SK;Bhikadiya C;Bi C;Bittrich S;Chen L;Crichlow GV;Christie CH;Dalenberg K;Di Costanzo L;Duarte JM;Dutta S;Feng Z;Ganesan S;Goodsell DS;Ghosh S;Green RK;Guranović V;Guzenko D;Hudson BP;Lawson CL;Liang Y;Lowe R;Namkoong H;Peisach E;Persikova I;Randle C;Rose A;Rose Y;Sali A;Segura J;Sekharan M;Shao C;Tao YP;Voigt M;Westbrook JD;Young JY;Zardecki C;Zhuravleva M
通讯作者：
Zhuravleva M
影响因子：
7
作者：
Parks DH;Imelfort M;Skennerton CT;Hugenholtz P;Tyson GW
通讯作者：
Tyson GW
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y