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. 2023 Mar 10;9(10):eabo0234.
doi: 10.1126/sciadv.abo0234. Epub 2023 Mar 8.

Indigenous people from Amazon show genetic signatures of pathogen-driven selection

Cainã M Couto-Silva  1 , Kelly Nunes  1 , Gabriela Venturini  2   3 , Marcos Araújo Castro E Silva  1   4 , Lygia V Pereira  1 , David Comas  4 , Alexandre Pereira  2   3 , Tábita Hünemeier  1   5
Affiliations

Indigenous people from Amazon show genetic signatures of pathogen-driven selection

Cainã M Couto-Silva et al. Sci Adv. .

Abstract

Ecological conditions in the Amazon rainforests are historically favorable for the transmission of numerous tropical diseases, especially vector-borne diseases. The high diversity of pathogens likely contributes to the strong selective pressures for human survival and reproduction in this region. However, the genetic basis of human adaptation to this complex ecosystem remains unclear. This study investigates the possible footprints of genetic adaptation to the Amazon rainforest environment by analyzing the genomic data of 19 native populations. The results based on genomic and functional analysis showed an intense signal of natural selection in a set of genes related to Trypanosoma cruzi infection, which is the pathogen responsible for Chagas disease, a neglected tropical parasitic disease native to the Americas that is currently spreading worldwide.

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Figures

Fig. 1.
Fig. 1.. PBS-windowed scores for target genes.
Log10 of PBS P values around the (A) PPP3CA and (B) NOS1AP and DYNC1I1 genes, chromosomes 1 and 4, respectively. Graphs show up to 4 Mb away from the initial and final gene position. Pink shadow areas correspond to 300 kb of the gene limit description. All these genes have the highest PBS values for their respective chromosomes.
Fig. 2.
Fig. 2.. Reduction in PPP3CA levels significantly inhibited iPS-CM T. cruzi infection.
(A) Number of intracellular parasites per 100 cells after 24 hours of infection showing a reduction of ~25% in parasite numbers in cells with lower expression of PPP3CA (red). Dots show the number of parasites in 100 cells for each well analyzed. The bars show the mean and SEM. Student’s t test was used to compare groups. (B) Representative images of iPS-CM transduced with scramble shRNA (top) and shRNA targeting PPP3CA after 24 hours of infection with T. cruzi expressing GFP (green). Nuclei were labeled with DAPI (gray), and actin was labeled with phalloidin (red).
Fig. 3.
Fig. 3.. High-frequency distribution of the putatively selected PPP3CA allele.
The yellow area on the map represents the endemic region of Chagas disease. The orange area represents the distribution of the putatively selected allele (rs2659540 G>A) in the studied populations.
See this image and copyright information in PMC

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References

    1. Llamas B., Fehren-Schmitz L., Valverde G., Soubrier J., Mallick S., Rohland N., Nordenfelt S., Valdiosera C., Richards S. M., Rohrlach A., Romero M. I. B., Espinoza I. F., Cagigao E. T., Jiménez L. W., Makowski K., Reyna I. S. L., Lory J. M., Torrez J. A. B., Rivera M. A., Burger R. L., Ceruti M. C., Reinhard J., Wells R. S., Politis G., Santoro C. M., Standen V. G., Smith C., Reich D., Ho S. Y. W., Cooper A., Haak W., Ancient mitochondrial DNA provides high-resolution time scale of the peopling of the Americas. Sci. Adv. 2, e1501385 (2016). - PMC - PubMed
    1. Acuña-Alonzo V., Flores-Dorantes T., Kruit J. K., Villarreal-Molina T., Arellano-Campos O., Hünemeier T., Moreno-Estrada A., Ortiz-López M. G., Villamil-Ramírez H., León-Mimila P., Villalobos-Comparan M., Jacobo-Albavera L., Ramírez-Jiménez S., Sikora M., Zhang L.-H., Pape T. D., Granados-Silvestre M. d. A., Montufar-Robles I., Tito-Alvarez A. M., Zurita-Salinas C., Bustos-Arriaga J., Cedillo-Barrón L., Gómez-Trejo C., Barquera-Lozano R., Vieira-Filho J. P., Granados J., Romero-Hidalgo S., Huertas-Vázquez A., González-Martín A., Gorostiza A., Bonatto S. L., Rodríguez-Cruz M., Wang L., Tusié-Luna T., Aguilar-Salinas C. A., Lisker R., Moises R. S., Menjivar M., Salzano F. M., Knowler W. C., Bortolini M. C., Hayden M. R., Baier L. J., Canizales-Quinteros S., A functional ABCA1 gene variant is associated with low HDL-cholesterol levels and shows evidence of positive selection in Native Americans. Hum. Mol. Genet. 19, 2877–2885 (2010). - PMC - PubMed
    1. Hünemeier T., Amorim C. E. G., Azevedo S., Contini V., Acuña-Alonzo V., Rothhammer F., Dugoujon J.-M., Mazières S., Barrantes R., Villarreal-Molina M. T., Paixão-Côrtes V. R., Salzano F. M., Canizales-Quinteros S., Ruiz-Linares A., Bortolini M. C., Evolutionary responses to a constructed niche: Ancient Mesoamericans as a model of gene-culture coevolution. PLOS ONE 7, e38862 (2012). - PMC - PubMed
    1. Amorim C. E. G., Nunes K., Meyer D., Comas D., Bortolini M. C., Salzano F. M., Hünemeier T., Genetic signature of natural selection in first Americans. Proc. Natl. Acad. Sci. U.S.A. 114, 2195–2199 (2017). - PMC - PubMed
    1. Lindo J., Haas R., Hofman C., Apata M., Moraga M., Verdugo R. A., Watson J. T., Viviano Llave C., Witonsky D., Beall C., Warinner C., Novembre J., Aldenderfer M., Di Rienzo A., The genetic prehistory of the Andean highlands 7000 years BP though European contact. Sci. Adv. 4, eaau4921 (2018). - PMC - PubMed
-