Native American genetic ancestry and pigmentation allele contributions to skin color in a caribbean population
Abstract
Our interest in the genetic basis of skin color variation between populations led us to seek a Native American population with genetically African admixture but low frequency of European light skin alleles. Analysis of 458 genomes from individuals residing in the Kalinago territory of the Commonwealth of Dominica showed approximately 55% Native American, 32% African, and 12% European genetic ancestry, the highest Native American genetic ancestry among Caribbean populations to date. Skin pigmentation ranged from 20 to 80 melanin units, averaging 46. Three albino individuals were determined to be homozygous for a causative multi-nucleotide polymorphism OCA2NW273KV contained within a haplotype of African origin; its allele frequency was 0.03 and single allele effect size was -8 melanin units. Derived allele frequencies of SLC24A5A111T and SLC45A2L374F were 0.14 and 0.06, with single allele effect sizes of -6 and -4, respectively. Native American genetic ancestry by itself reduced pigmentation by more than 20 melanin units (range 24 - 29). The responsible hypopigmenting genetic variants remain to be identified, since none of the published polymorphisms predicted in prior literature to affect skin color in Native Americans caused detectable hypopigmentation in the Kalinago.
Data availability
The whole exome sequencing and whole genome SNP genotyping data underlying this article cannot be shared publicly due to the privacy of individuals and stipulation by the Kalinago community. Only de-identified filtered SNP data used in analyses will be shared. Additional data will be shared on request to the corresponding author, pending approval from the Kalinago Council.M-index and specific genotyping data (SLC24A5 A111T, SLC45A2 L374F, OCA2 NW273KV and OCA2 305W) and genotyping data for Admixture have been uploaded to Dryad https://doi.org/10.5061/dryad.sf7m0cg7zThe data cannot be used for any commercial purposes.We did not create any new software or script for analysis.
-
Native American Genetic Ancestry and Pigmentation Allele Contributions to Skin Color in a Caribbean PopulationDryad Digital Repository, doi:10.5061/dryad.sf7m0cg7z.
-
A map of human genome variation from population-scale sequencinghttps://www.internationalgenome.org/data.
-
Reconstructing Native American population historydoi:10.1038/nature11258.
Article and author information
Author details
Funding
Hershey Rotary Club
- Khai C Ang
Jake Gittlen Laboratories for Cancer Research
- Keith C Cheng
Penn State College of Medicine Department of Pathology
- Keith C Cheng
The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was reviewed and approved by the Kalinago council and institutional review boards of Penn State University (29269EP), Ross University, and the Dominica Ministry of Health (H125). Informed consent was obtained from each participant enrolled in the study, and in the case of minors, consent was also obtained from a parent or guardian.
Copyright
© 2023, Ang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,444
- views
-
- 217
- downloads
-
- 1
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Ecology
- Evolutionary Biology
While host phenotypic manipulation by parasites is a widespread phenomenon, whether tumors, which can be likened to parasite entities, can also manipulate their hosts is not known. Theory predicts that this should nevertheless be the case, especially when tumors (neoplasms) are transmissible. We explored this hypothesis in a cnidarian Hydra model system, in which spontaneous tumors can occur in the lab, and lineages in which such neoplastic cells are vertically transmitted (through host budding) have been maintained for over 15 years. Remarkably, the hydras with long-term transmissible tumors show an unexpected increase in the number of their tentacles, allowing for the possibility that these neoplastic cells can manipulate the host. By experimentally transplanting healthy as well as neoplastic tissues derived from both recent and long-term transmissible tumors, we found that only the long-term transmissible tumors were able to trigger the growth of additional tentacles. Also, supernumerary tentacles, by permitting higher foraging efficiency for the host, were associated with an increased budding rate, thereby favoring the vertical transmission of tumors. To our knowledge, this is the first evidence that, like true parasites, transmissible tumors can evolve strategies to manipulate the phenotype of their host.
-
- Evolutionary Biology
- Microbiology and Infectious Disease
Accurate estimation of the effects of mutations on SARS-CoV-2 viral fitness can inform public-health responses such as vaccine development and predicting the impact of a new variant; it can also illuminate biological mechanisms including those underlying the emergence of variants of concern. Recently, Lan et al. reported a model of SARS-CoV-2 secondary structure and its underlying dimethyl sulfate reactivity data (Lan et al., 2022). I investigated whether base reactivities and secondary structure models derived from them can explain some variability in the frequency of observing different nucleotide substitutions across millions of patient sequences in the SARS-CoV-2 phylogenetic tree. Nucleotide basepairing was compared to the estimated ‘mutational fitness’ of substitutions, a measurement of the difference between a substitution’s observed and expected frequency that is correlated with other estimates of viral fitness (Bloom and Neher, 2023). This comparison revealed that secondary structure is often predictive of substitution frequency, with significant decreases in substitution frequencies at basepaired positions. Focusing on the mutational fitness of C→U, the most common type of substitution, I describe C→U substitutions at basepaired positions that characterize major SARS-CoV-2 variants; such mutations may have a greater impact on fitness than appreciated when considering substitution frequency alone.