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Highland native Andeans have resided at altitude for millennia. They display high aerobic capacity (VO 2 max) at altitude, which may be a reflection of genetic adaptation to hypoxia. Previous genomewide (GW) scans for natural selection have nominated Egl-9 homolog 1 gene ( EGLN1 ) as a candidate gene. The encoded protein, EGLN1/PHD2, is an O 2 sensor that controls levels of the Hypoxia Inducible Factor-α (HIF-α), which regulates the cellular response to hypoxia. From GW association and analysis of covariance performed on a total sample of 429 Peruvian Quechua and 94 US lowland referents, we identified 5 EGLN1 SNPs associated with higher VO 2 max (L⋅min −1 and mL⋅min −1 ⋅kg −1 ) in hypoxia (rs1769793, rs2064766, rs2437150, rs2491403, rs479200). For 4 of these SNPs, Quechua had the highest frequency of the advantageous (high VO 2 max) allele compared with 25 diverse lowland comparison populations from the 1000 Genomes Project. Genotype effects were substantial, with high versus low VO 2 max genotype categories differing by ∼11% (e.g., for rs1769793 SNP genotype TT = 34.2 mL⋅min −1 ⋅kg −1 vs. CC = 30.5 mL⋅min −1 ⋅kg −1 ). To guard against spurious association, we controlled for population stratification. Findings were replicated for EGLN1 SNP rs1769793 in an independent Andean sample collected in 2002. These findings contextualize previous reports of natural selection at EGLN1 in Andeans, and support the hypothesis that natural selection has increased the frequency of an EGLN1 causal variant that enhances O 2 delivery or use during exercise at altitude in Peruvian Quechua.
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Genetic diversity and population structure of Leishmania (Viannia) braziliensis in the Peruvian jungle
Background Human cutaneous leishmaniasis caused by Leishmania (Viannia) braziliensis is highly prevalent in the Peruvian jungle, where it affects military forces deployed to fight against drug trafficking and civilian people that migrate from the highland to the lowland jungle for economic activities such as mining, agriculture, construction, and chestnut harvest. We explored the genetic diversity and population structure of 124 L . (V . ) braziliensis isolates collected from the highland (Junín, Cusco, and Ayacucho) and lowland Peruvian jungle (Loreto, Ucayali, and Madre de Dios). All samples were genotyped using Multilocus Microsatellite Typing (MLMT) of ten highly polymorphic markers. Principal findings High polymorphism and genetic diversity were found in Peruvian isolates of L . (V . ) braziliensis . Most markers are not in Hardy-Weinberg equilibrium; this deviation is most likely caused by local inbreeding, as shown by the positive F IS values. Linkage Disequilibrium in subpopulations was not strong, suggesting the reproduction was not strictly clonal. Likewise, for the first time, two genetic clusters of this parasite were determined, distributed in both areas of the Peruvian jungle, which suggested a possible recent colonization event of the highland jungle from the lowland jungle. Conclusions L . (V . ) braziliensis exhibits considerable genetic diversity with two different clusters in the Peruvian jungle. Migration analysis suggested a colonization event between geographical areas of distribution. Although no human migration was observed at the time of sampling, earlier displacement of humans, reservoirs, or vectors could have been responsible for the parasite spread in both regions.
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- Award ID(s):
- 1564822
- PAR ID:
- 10348125
- Editor(s):
- Schönian, Gabriele
- Date Published:
- Journal Name:
- PLOS Neglected Tropical Diseases
- Volume:
- 16
- Issue:
- 5
- ISSN:
- 1935-2735
- Page Range / eLocation ID:
- e0010374
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1371/journal.pntd.0010374
