TY - JOUR
T1 - Identification of New Helicobacter pylori Subpopulations in Native Americans and Mestizos From Peru
AU - Gutiérrez-Escobar, Andrés Julián
AU - Velapatiño, Billie
AU - Borda, Victor
AU - Rabkin, Charles S.
AU - Tarazona-Santos, Eduardo
AU - Cabrera, Lilia
AU - Cok, Jaime
AU - Hooper, Catherine C.
AU - Jahuira-Arias, Helena
AU - Herrera, Phabiola
AU - Noureen, Mehwish
AU - Wang, Difei
AU - Romero-Gallo, Judith
AU - Tran, Bao
AU - Peek, Richard M.
AU - Berg, Douglas E.
AU - Gilman, Robert H.
AU - Camargo, M. Constanza
N1 - Funding Information:
This study was supported by the Extramural (Grants numbers, R01 DK 58587, R01 CA 77955, P01 CA 116087, and P30 DK 058404) and Intramural Research Program of the U.S. National Cancer Institute. ET-S was supported by the Brazilian National Council for Scientific and Technological Development (CNPq) and the Department of Science and Technology of the Brazilian Ministry of Health (MS-DECIT).
Funding Information:
We gratefully acknowledge laboratory assistance from Castle Raley, Xiongfong Chen, Bailey Kessing, and Yongmei Zhao from the National Cancer Institute?s Center for Cancer Research at the Frederick National Laboratory for Cancer Research. We also acknowledge expert advice on the ancestry analysis provided by Roberto Torres from the Mexican Institute of Social Security. Funding. This study was supported by the Extramural (Grants numbers, R01 DK 58587, R01 CA 77955, P01 CA 116087, and P30 DK 058404) and Intramural Research Program of the U.S. National Cancer Institute. ET-S was supported by the Brazilian National Council for Scientific and Technological Development (CNPq) and the Department of Science and Technology of the Brazilian Ministry of Health (MS-DECIT).
Publisher Copyright:
© Copyright © 2020 Gutiérrez-Escobar, Velapatiño, Borda, Rabkin, Tarazona-Santos, Cabrera, Cok, Hooper, Jahuira-Arias, Herrera, Noureen, Wang, Romero-Gallo, Tran, Peek, Berg, Gilman and Camargo.
PY - 2020/12/14
Y1 - 2020/12/14
N2 - Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.
AB - Region-specific Helicobacter pylori subpopulations have been identified. It is proposed that the hspAmerind subpopulation is being displaced from the Americans by an hpEurope population following the conquest. Our study aimed to describe the genomes and methylomes of H. pylori isolates from distinct Peruvian communities: 23 strains collected from three groups of Native Americans (Asháninkas [ASHA, n = 9], Shimaas [SHIM, n = 5] from Amazonas, and Punos from the Andean highlands [PUNO, n = 9]) and 9 modern mestizos from Lima (LIM). Closed genomes and DNA modification calls were obtained using SMRT/PacBio sequencing. We performed evolutionary analyses and evaluated genomic/epigenomic differences among strain groups. We also evaluated human genome-wide data from 74 individuals from the selected Native communities (including the 23 H. pylori strains donors) to compare host and bacterial backgrounds. There were varying degrees of hspAmerind ancestry in all strains, ranging from 7% in LIM to 99% in SHIM. We identified three H. pylori subpopulations corresponding to each of the Native groups and a novel hspEuropePeru which evolved in the modern mestizos. The divergence of the indigenous H. pylori strains recapitulated the genetic structure of Native Americans. Phylogenetic profiling showed that Orthogroups in the indigenous strains seem to have evolved differentially toward epigenomic regulation and chromosome maintenance, whereas OGs in the modern mestizo (LIM) seem to have evolved toward virulence and adherence. The prevalence of cagA+/vacA s1i1m1 genotype was similar across populations (p = 0.32): 89% in ASHA, 67% in PUNO, 56% in LIM and 40% in SHIM. Both cagA and vacA sequences showed that LIM strains were genetically differentiated (p < 0.001) as compared to indigenous strains. We identified 642 R-M systems with 39% of the associated genes located in the core genome. We found 692 methylation motifs, including 254 population-specific sequences not previously described. In Peru, hspAmerind is not extinct, with traces found even in a heavily admixed mestizo population. Notably, our study identified three new hspAmerind subpopulations, one per Native group; and a new subpopulation among mestizos that we named hspEuropePeru. This subpopulation seems to have more virulence-related elements than hspAmerind. Purifying selection driven by variable host immune response may have shaped the evolution of Peruvian subpopulations, potentially impacting disease outcomes.
KW - Amerindians
KW - Peru
KW - ancestry
KW - hspAmerind
KW - indigenous
KW - mestizo
UR - http://www.scopus.com/inward/record.url?scp=85098290814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85098290814&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2020.601839
DO - 10.3389/fmicb.2020.601839
M3 - Article
C2 - 33381095
AN - SCOPUS:85098290814
SN - 1664-302X
VL - 11
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
M1 - 601839
ER -