A team of geneticists led by Sarah Tishkoff has demonstrated the extensive variation in skin color within Africa, ranging from shades as light as some Asians to the darkest skin tones globally. This article delves into the genetic factors contributing to the diversity of skin pigmentation in Ethiopia, exploring the roles of Eurasian gene flow, natural selection, and specific genes associated with lighter skin tones.
Global distribution of skin pigmentation and average UV radiation levels.
Genetic Diversity and Linguistic Stratification in Ethiopia
Ethiopia's unique genetic makeup reflects a complex history of interactions between Sub-Saharan Africa, North Africa, and Eurasia. This synthesis has gradually crystallized since the time of Old Kingdom Egypt. Sometimes you can judge a book by its cover, and you might say Ethiopia’s various ethnicities lie visibly equidistant in physical characteristics from Arabian populations and Sub-Saharan African ones.
The ethnogenesis of this mix of peoples is only now freshly within our grasp, thanks to the tools of genomics, as ancient DNA finally exposes roots buried far beyond the reach of history or archaeology. The Afro-Asiatic languages spoken by most Ethiopians further reinforce the case for a deep connection to Arabia. The Semitic languages of the region are related to southern Arabia’s indigenous dialects like Mehri in Yemen, as well as extinct languages like the Sabaean spoken by the Biblical Queen of Sheba.
Genetic data allows us to move beyond intuitive suppositions. Humans and their ancestors have traversed the Ethiopian landscape for millions of years, and present-day Ethiopians show great cultural, linguistic, and historical diversity, which makes them essential for understanding African variability and human origins. Ethiopian genetic diversity reveals linguistic stratification and complex influences on the Ethiopian gene pool.
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To take a first stab at situating Ethiopians in the landscape of African genetic variation I assembled a dataset of:
- 10 Bantus from Northeast Africa (I believe these to be Kenyan Kikuyus mostly)
- 21 Luhya Bantus form Kenya
- 8 Bantus from South Africa (likely Zulu)
- 19 Druze Arabs from Lebanon
- 12 Egyptian Muslims
- 43 Esan from Nigeria
- 7 Ethiopian Amhara
- 7 Ethiopian Oromo
- 5 Ethiopian Tigray
- 12 Ethiopian Jews
- 19 Iranians
- 54 Yemenis
- 15 Yemeni Jews
Pruning the marker set down to shared SNPs (single nucleotide polymorphisms) present in all individuals gives us 120,000 SNPs, plenty to run principal component analysis (PCA) and admixture analysis.
The plot of PC 1 against PC 2 for the two foremost dimensions of variation in the data illustrates the stark differentiation of Eurasian and African populations along PC 1. This axis of variation explains ten times as much variation as PC 2, which differentiates Ethiopians from literally all other human populations. The fact that there is an Ethiopian/non-Ethiopian axis nevertheless indicates something unique in the genetics of Ethiopian peoples.
In the bar plot above, each slender vertical line represents one of the 232 individuals’ genotypes, with the proportional ancestral components stacked vertically, assuming a set of diverged populations, K. I ran the dataset above in an unsupervised mode with K = 4, meaning essentially that I did not price in any prior fixed population information, but just asked the model to assess each individual as a combination of up to four hypothetical component populations that in combination would have to account for all ancestry in the 232 samples. What you immediately see is that some groups are most parsimoniously modeled as descending from just one ancestral population. Within Ethiopian samples, this component is most prevalent in the Oromo, which makes geographical sense since the Oromo lands sprawl across the country’s south and east, and thus interface with both Sudanese Nilo-Saharan speakers and Kenyan Bantu speakers.
The light-blue cluster is maximized in Yemenis and Jewish Yemenis, and seems to reflect Arabian heritage, while the deep teal-blue cluster shows up more in populations to the north and east. While Egyptians are split between these two Eurasian clusters, the Ethiopian populations’ ancestry from Eurasians appears almost exclusively in the form of the light blue cluster most common in Yemenis. This accords with the PCA as well, where Yemenis and Yemeni Jews are both shifted towards Ethiopians compared to Iranians or Druze.
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A study genotyped 235 individuals from ten Ethiopian and two neighboring (South Sudanese and Somali) populations on an Illumina Omni 1M chip. Genotypes were compared with published data from several African and non-African populations. Principal-component and STRUCTURE-like analyses confirmed substantial genetic diversity both within and between populations, and revealed a match between genetic data and linguistic affiliation.
The non-African component, which includes the SLC24A5 allele associated with light skin pigmentation in Europeans, may represent gene flow into Africa, which we estimate to have occurred ∼3 thousand years ago (kya). Given that little genetic information on Ethiopian populations was available in advance, we sought to analyze a broad sample of 188 Ethiopians from ten diverse populations.
The samples genotyped included representatives of a range of geographical regions and all four linguistic groups (Semitic, Cushitic, Omotic, and Nilotic). The populations sampled (numbers) were the Semitic-speaking Amhara (26) and Tigray (21); the Cushitic-speaking Oromo (21), Ethiopian Somali (17), and Afar (12); the Omotic-speaking Ari Cultivators (24), Ari Blacksmiths (17), and Wolayta (8); and the Nilotic-speaking Gumuz (19) and Anuak (23).
The first PC of the African samples separates sub-Saharan Africans from North Africans, with Ethiopians positioned between them, whereas the second and third components separate the hunter-gatherers (click speakers and Pygmies) and the East Africans, respectively. Both plots separate the Ethiopian samples according to their linguistic origin. This linguistic clustering appears to be more important than geographical structure, especially for the Semitic and Cushitic populations. Remarkably, the Ethiopian clusters, taken together, span half of the space delimited by all the African populations and surround the Maasai from Kenya.
ADMIXTURE was applied to the same African data set, with the addition of the HGDP French as a reference group for the non-African component. The best-supported clustering (K = 7, Figure 1C) divided the Ethiopians into two main groups: the Semitic-Cushitic Ethiopians stand out as a relatively uniform set of individuals characterized by a strong (40%-50%) non-African component (light blue in Figure 1C) and an African component split between a broad East African (purple in Figure 1C) and an apparently Ethiopia-specific component (yellow); the Nilotic and Omotic Ethiopians show little or no non-African component and are instead characterized by eastern (purple and yellow) or western (dark red) African components, with some traces of additional components.
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The yellow and purple components represent the major proportion of the African component in the Egyptian Afro-Asiatic population, but are less predominant than the red West African component among northwestern African populations who also speak Afro-Asiatic languages. As shown in Figure 1E, both PC1 and PC3 strongly correlate (both r2 values are above 0.98) with the blue component.
The Genetics of Skin Pigmentation
Skin pigmentation is regulated by genes underlying the development of melanocytes and melanosome biogenesis. Recent genome-wide genetic studies of skin pigmentation in African populations have advanced our understanding of pigmentation biology and human evolutionary history. Skin color is a highly heritable human trait, and global variation in skin pigmentation has been shaped by natural selection, migration and admixture.
The majority of studies examining the genetics of skin pigmentation have been conducted in European and Asian populations, and African populations are vastly underrepresented. For example, the KhoeSan hunter-gatherers in Botswana have relatively light skin, while Nilo-Saharan-speaking populations from East Africa have some of the darkest pigmented skin on Earth. Human skin color is determined by the composition, abundance and distribution of melanin pigments, which are biopolymers derived from tyrosine.
Melanin is synthesized and stored in lysosome-like organelles called melanosomes, which are generated in melanocytes and transferred to surrounding keratinocytes. An important goal of evolutionary genetics is to identify the variants and genes underlying phenotypic evolution and local adaptation.
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Genes Influencing Skin Pigmentation in Africans
Several recent studies have examined pigmentation in African populations, providing novel insights into the evolution of skin color.
SLC24A5
SLC24A5 encodes a cation exchanger in melanosomes and was first confirmed to affect skin pigmentation in zebrafish. A derived, nonsynonymous mutation (rs1426654 (A), Ala111Thr) in SLC24A5 associated with light skin color has swept to near fixation in Europeans due to positive selection.
Recent studies show that this SLC24A5 allele is also associated with light skin in Africans. The authors show that rs1426654 is common in East African populations with high levels of Afroasiatic ancestry, and that rs1426654 likely introgressed into these populations from a Eurasian source >5 kya. Further, SLC24A5 likely experienced positive selection in East Africa after this admixture event.
OCA2 and HERC2
The OCA2 gene impacts skin pigmentation by regulating melanosome pH, and mutations in this gene cause oculocutaneous albinism type II (OCA2). HERC2 is adjacent to OCA2 on chromosome 15, and although HERC2 does not directly impact pigmentation, regulatory elements in HERC2 can influence expression of OCA2.
Within Africans, several novel variants in this region associated with skin pigmentation have recently been described. The derived allele of a synonymous variant in OCA2 (rs1800404 (T)), associated with light pigmentation, is at high frequency (>70%) in Europeans and the KhoeSan from Botswana.
DDB1
The damage-specific DNA binding protein (DDB1) gene functions in DNA repair after UV-induced damage. Variants in and around this gene were also significantly associated with African skin pigmentation in a GWAS of ethnically diverse African people from Tanzania, Botswana and Ethiopia. The derived allele of rs7948623 (T), associated with dark pigmentation, is at highest global frequency in East African populations with Nilo-Saharan ancestry, who inhabit high UVR environments and have darkly pigmented skin.
MFSD12
The derived alleles at the synonymous variant rs56203814 (T) and the intronic variant rs10424065 (T) significantly associate with dark pigmentation and are at highest frequency in East Africans with Nilo-Saharan ancestry. Increased MFSD12 expression also promotes melanoma cell proliferation and may be an important therapeutic target for melanoma.
Variants at MFSD12 also have highly divergent allele frequencies between East Africans and Europeans as measured by FST, consistent with a signature of local adaptation.
MC1R and TYRP1
Some early studies of skin pigmentation genes focus on the melanocortin 1 receptor (MC1R), which controls the type of melanin produced (eumelanin or pheomelanin) by melanocytes. These data suggest strong purifying selection acting at MC1R within Africa, where any deviation from the eumelanin-producing form of the gene, which leads to darker pigmentation, is strongly selected against.
TYRP1 was the first gene found to be associated with oculocutaneous albinism in Africans, and the rs387906560 frameshift mutation (Lys368SerfsTer17) in TYRP1 causes oculocutaneous albinism 3 (OCA3 or rufous albinism). TYRP1 shows a signature of strong positive selection in a Senegalese population, as indicated by a significantly negative Tajima’s D value.
The Role of Skin Pigmentation
Skin pigmentation is an evolutionary adaptation to the various UV radiation levels around the world. Eumelanin protects tissues and DNA from radiation damage by UV light.
Humans with light skin pigmentation living in low sunlight environments experience increased vitamin D synthesis compared to humans with dark skin pigmentation due to the ability to absorb more sunlight. Almost every part of the human body, including the skeleton, the immune system, and brain requires vitamin D.
The clinal (gradual) distribution of skin pigmentation observable in the Eastern hemisphere, and to a lesser extent in the Western hemisphere, is one of the most significant characteristics of human skin pigmentation. Variations in the KITL gene have been positively associated with about 20% of melanin concentration differences between African and non-African populations.
Melanin formation pathway in melanocytes.
The Evolution of Light Skin in Eurasians
After the ancestors of West Eurasians and East Eurasians diverged more than 40,000 years ago, lighter skin tones evolved independently in a subset of each of the two populations. The light skin variants of SLC24A5 and SLC45A2 were present in Anatolia by 9,000 years ago, where they became associated with the Neolithic Revolution.
Furthermore, the SLC24A5 gene linked with light pigmentation in Europeans was introduced into East Africa from Europe over five thousand years ago. These alleles can now be found in the San, Ethiopians, and Tanzanian populations with Afro-Asiatic ancestry. The A111T mutation in the SLC24A5 gene predominates in populations with Western Eurasian ancestry.
Conclusion
The genetic landscape of Ethiopian skin pigmentation is a testament to the complex interplay of migration, admixture, and natural selection. The presence of both African and Eurasian genetic components, coupled with the adaptation to diverse environmental conditions, has resulted in a wide range of skin tones within the Ethiopian population. Future research should focus on expanding genetic studies to include more diverse African populations, which will further illuminate the intricate mechanisms underlying human skin pigmentation and its evolutionary history.
| Gene | Variant | Associated Pigmentation | Frequency in East Africans | Frequency in Europeans | Frequency in KhoeSan |
|---|---|---|---|---|---|
| SLC24A5 | rs1426654 (A) | Light | High | Near Fixation | Moderate |
| OCA2 | rs1800404 (T) | Light | Low | High | High |
| DDB1 | rs7948623 (T) | Dark | High | Low | Low |
| MFSD12 | rs56203814 (T) | Dark | High | Low | Low |
