Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

Wilde, Sandra; Timpson, Adrian; Kirsanow, Karola; Kaiser, Elke; Kayser, Manfred; Unterländer, Martina; Hollfelder, Nina; Potekhina, Inna; Schier, Wolfram; Thomas, Mark G.; Bürger, Joachim

doi:10.1073/pnas.1316513111

Cited by 246 publications

(255 citation statements)

References 65 publications

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“…6), suggesting that there are other genetic variants having a critical role in melanin formation in Asians (Edwards et al 2010). The observed directions of the selection differences suggest that mutated alleles of the variants involved in melanin formation were more favorably selected in non-African populations (Wilde et al 2014). …”

Section: Estimating Differences In Selectionmentioning

confidence: 99%

A probabilistic method for testing and estimating selection differences between populations

He¹,

Wang²,

Huang³

et al. 2015

Genome Res.

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Human populations around the world encounter various environmental challenges and, consequently, develop genetic adaptations to different selection forces. Identifying the differences in natural selection between populations is critical for understanding the roles of specific genetic variants in evolutionary adaptation. Although numerous methods have been developed to detect genetic loci under recent directional selection, a probabilistic solution for testing and quantifying selection differences between populations is lacking. Here we report the development of a probabilistic method for testing and estimating selection differences between populations. By use of a probabilistic model of genetic drift and selection, we showed that logarithm odds ratios of allele frequencies provide estimates of the differences in selection coefficients between populations. The estimates approximate a normal distribution, and variance can be estimated using genome-wide variants. This allows us to quantify differences in selection coefficients and to determine the confidence intervals of the estimate. Our work also revealed the link between genetic association testing and hypothesis testing of selection differences. It therefore supplies a solution for hypothesis testing of selection differences. This method was applied to a genome-wide data analysis of Han and Tibetan populations. The results confirmed that both the EPAS1 and EGLN1 genes are under statistically different selection in Han and Tibetan populations. We further estimated differences in the selection coefficients for genetic variants involved in melanin formation and determined their confidence intervals between continental population groups. Application of the method to empirical data demonstrated the outstanding capability of this novel approach for testing and quantifying differences in natural selection.

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Section: Estimating Differences In Selectionmentioning

confidence: 99%

A probabilistic method for testing and estimating selection differences between populations

He¹,

Wang²,

Huang³

et al. 2015

Genome Res.

View full text Add to dashboard Cite

show abstract

“…The biology of pigmented lesions is then discussed, including freckling, naevi and melanoma [4] . in the last 5,000-20,000 years [5] . The origin of modern humans can be traced to Africa around 200,000 years ago, followed by the expansion and subsequent colonization of the rest of the world around 50,000-60,000 years ago.…”

Section: Introductionmentioning

confidence: 99%

Skin Pigmentation Genetics for the Clinic

Ainger

Jagirdar²,

Lee³

et al. 2017

Dermatology

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Human pigmentation characteristics play an important role in the effects of sun exposure, skin cancer induction and disease outcomes. Several of the genes most important for this diversity are involved in the regulation and distribution of melanin pigmentation or enzymes involved in melanogenesis itself within the melanocyte cell present in the skin, hair and eyes. The single nucleotide polymorphisms and extended haplotypes within or surrounding these genes have been identified as risk factors for skin cancer, in particular, melanoma. These same polymorphisms have been under selective pressure leading towards lighter pigmentation in Europeans in the last 5,000-20,000 years that have driven the increase in frequency in modern populations. Although pigmentation is a polygenic trait, due to interactive and quantitative gene effects, strong phenotypic associations are readily apparent for these major genes. However, predictive value and utility are increased when considering gene polymorphism interactions. In melanoma, an increased penetrance is found in cases when pigmentation gene risk alleles such as MC1R variants are coincident with mutation of higher-risk melanoma genes including CDKN2A, CDK4 and MITF E318K, demonstrating an interface between the pathways for pigmentation, naevogenesis and melanoma. The clinical phenotypes associated with germline changes in pigmentation and naevogenic genes must be understood by clinicians, and will be of increasing relevance to dermatologists, as genomics is incorporated into the delivery of personalised medicine.

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“…To evaluate if changes in the DRD4 rs1800955 T allele frequency observed in the time transect can be explained by genetic drift, or if natural selection needs to be considered we used a forward simulation approach based on Wilde et al (Wilde et al 2014) that also allows the estimation of the selection coefficient (s). To reflect uncertainty in the ancient allele frequencies due to low sample size we first drew the allele frequency estimate for the oldest population (Early/Middle Archaic), from a random Beta (n p + 1,n q + 1) distribution, where n p and n q were equal to the number of the respective ancestral and derived allele, in each forward simulation.…”

Section: Methodsmentioning

confidence: 99%

“…As there is no evidence for a dominant or recessive mode of action for the SNP, an codominant model of inheritance was applied (Thomson et al 2014). Subsequently, the simulated distribution of allele frequencies at generation 0 were compared with those observed using the equation 1-2 × |0.5 -P|, where P is the proportion of simulated modern allele frequencies that are greater than that observed, yielding a two-tailed empirical P value for the observed allele frequency changes for all prior combinations tested (Voight et al 2005;Wilde et al 2014).…”

Section: Methodsmentioning

confidence: 99%

Ancient DNA Reveals That the Variability of the DRD4 -521 C/T SNP Associated with Novelty Seeking Behavior is Influenced by Selection in Western South American Populations

Rubira

Georges

Fehren‐Schmitz

2015

Adaptive Human Behavior and Physiology

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Certain Polymorphisms in the DRD4 gene have been associated with behavioral traits such as novelty seeking (NS), impulsivity, and ADHD. Research has suggested that these personality traits may affect individual fitness differently depending on social structure, subsistence patterns, and mobility. To test this hypothesis this study examines the diachronic change in the frequency of the C allele of the −521 C/T SNP in the DRD4 promoter region, thought to contribute to the NS phenotype, analyzing ancient DNA from pre-Columbian South America. We used a SBE PCR based approach to analyze the DRD4 SNP in 125 prehistoric samples dating from 8000 BP to the end of the pre-Columbian period and deriving from a diversity of socioeconomic environments. We performed forward simulations of genetic drift with selection to test if difference in allele frequencies over time can solely be explained by random evolutionary processes or if selection has to be considered. Further, we performed statistical tests to explore possible association of observed differences with socioeconomic or environmental factors. DRD4 genotypes for 79 individuals were obtained. We find signals of slight selection acting on the DRD4-521 T allele. While the postulated association between the −521 C/T DRD4 SNP with modes of subsistence was not confirmed the results suggest a possible impact of socioeconomic complexity Adaptive Human Behavior and Physiology (2016) 2:77-91 DOI 10.1007/s40750-015-0033-5 Electronic

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Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

Cited by 246 publications

References 65 publications

A probabilistic method for testing and estimating selection differences between populations

A probabilistic method for testing and estimating selection differences between populations

Skin Pigmentation Genetics for the Clinic

Ancient DNA Reveals That the Variability of the DRD4 -521 C/T SNP Associated with Novelty Seeking Behavior is Influenced by Selection in Western South American Populations

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