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. 2023 Jan 24;26(2):106034.
doi: 10.1016/j.isci.2023.106034. eCollection 2023 Feb 17.

Genomic evidence for adaptation to tuberculosis in the Andes before European contact

Sophie K Joseph  1 , Nicola Rambaldi Migliore  2 , Anna Olivieri  2 , Antonio Torroni  2 , Amanda C Owings  3 , Michael DeGiorgio  4 , Wladimir Galarza Ordóñez  5 , J J Ortiz Aguilú  6 , Fabricio González-Andrade  7 , Alessandro Achilli  2 , John Lindo  1
Affiliations

Genomic evidence for adaptation to tuberculosis in the Andes before European contact

Sophie K Joseph et al. iScience. .

Abstract

Most studies focusing on human high-altitude adaptation in the Andean highlands have thus far been focused on Peruvian populations. We present high-coverage whole genomes from Indigenous people living in the Ecuadorian highlands and perform multi-method scans to detect positive natural selection. We identified regions of the genome that show signals of strong selection to both cardiovascular and hypoxia pathways, which are distinct from those uncovered in Peruvian populations. However, the strongest signals of selection were related to regions of the genome that are involved in immune function related to tuberculosis. Given our estimated timing of this selection event, the Indigenous people of Ecuador may have adapted to Mycobacterium tuberculosis thousands of years before the arrival of Europeans. Furthermore, we detect a population collapse that coincides with the arrival of Europeans, which is more severe than other regions of the Andes, suggesting differing effects of contact across high-altitude populations.

Keywords: Anthropology; Evolutionary biology; Human genetics.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

None
Graphical abstract
Figure 1
Figure 1
Demographic analyses (A) Map of population locations. populations. (B) Principal components analysis showing first two principal components, including individuals from this study and individuals from Europe, East Asia, and the Americas obtained from the SGDP dataset. (C) Maximum likelihood trees generated by TreeMix showing ancestry relationships between Ecuadorian groups and individuals in the SGDP dataset. (D) Changes in effective population size. According to the model, both the Kichwa and Loja populations suffer a population collapse that coincides with arrival of the Spanish to the Andean highlands. (E) Visualization of cluster analysis at K = 6, which exhibited the lowest BIC value.
Figure 2
Figure 2
Selection scans highlighting the strongest signals of positive selection Ohana selscan Manhattan plot and histogram of the allele distribution of the corresponding likelihood ratio (lle ratio) for the Kichwa (A) and Loja (B). iHS Manhattan plot and histogram of the allele distribution at the corresponding-log10(pvalue) for the Kichwa (C) and the Loja (D). Manhattan plot of the log composite likelihood ratio (Λ) from the saltiLASSI program and histogram of the allele distribution at the corresponding Λ for the Kichwa (E) and the Loja (F).
Figure 3
Figure 3
Allele trajectories and selection strength (A) Estimated allele trajectory over time (generations before present) for the allele associated with the PDE11A gene putatively under selection in the northern Kichwa. (B) Estimated allele trajectory for the allele associated with the SLC8A1 gene putatively under selection in the Loja population. Both alleles are known binding sites for the CEBPB transcription factor, implicated in the early anti-TB response via its role in the proliferation of monocyte macrophages.
Figure 4
Figure 4
Visualization of major lines of evidence relating to alleles under a high probability of positive selection associated with anti-TB immune response Associated alleles are listed in Tables S3 and S4. Created with www.BioRender.com.
See this image and copyright information in PMC

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