Investigating Genes Related to the Evolution of Indigenous American Skin Pigmentation

Open Access
Quillen, Ellen Elizabeth
Graduate Program:
Doctor of Philosophy
Document Type:
Date of Defense:
August 04, 2010
Committee Members:
  • Mark Shriver, Dissertation Advisor
  • Mark Shriver, Committee Chair
  • Kenneth Monrad Weiss, Committee Member
  • David Andrew Puts, Committee Member
  • David John Vandenbergh, Committee Member
  • Nina G Jablonski, Committee Member
  • skin color
  • human evolution
  • natural selection
  • Colombia
  • pigmentation
  • population genetics
The genetic study of human pigmentation is fundamental to anthropology because pigmentation represents an enormously variable phenotype present in all humans shaped and reshaped over the history of the hominid lineage by the forces of evolution. Skin pigmentation is among the most conspicuously varying traits among individuals and populations and must be understood in the context of the evolutionary history of the human species. As a population moves into a new environment, natural selection acts on both existing and newly emerging genetic variation in the population. There is a clear north-south gradient of skin pigmentation across the globe, with populations at higher latitudes having less melanin in their skin on average than populations at lower latitudes. This distribution suggests that skin pigmentation has been under strong selection as human populations spread throughout Africa and eventually around the world. There are a number of hypotheses to explain why this distribution occurs, predominantly rooted in the distribution of ultra-violet radiation (UVR). Previous researchers have employed statistical methods which detect distributions of allele frequencies and genomic signatures inconsistent with neutral evolution. These methods have identified skin pigmentation genes in a number of Old World populations that appear to have undergone selection. This dissertation reports on the first genome-wide analysis of evidence for selection at skin pigmentation genes in New World populations. From 76 initial pigmentation candidate genes, four tests of selection – Locus-Specific Branch Length (LSBL), Log of the Ratio of Heterozygosities (lnRH), Tajima’s D, and a heuristic haplotypes analysis – were used to identify fourteen pigmentation genes with signatures of selection unique to Indigenous American populations. Based on the evidence of selection, a logical hypothesis is these genes may play a role in determining skin color in Indigenous American populations. To test this hypothesis, admixture linkage analysis was performed in several samples of European and Indigenous American ancestry. Admixture linkage analysis exploits a number of unique properties of admixed populations. In an admixed population, genes influencing skin pigmentation variation between the Indigenous American and European parental populations will have a higher proportion of Indigenous American alleles than expected in individuals with darker skin pigmentation. Most importantly, the use of admixed populations allows for the appearance of heterozygotes at loci where alternate alleles may be fixed in the parental populations. To characterize these admixed populations, ancestry informative markers (AIMs) were genotyped in the samples. In particular, the distribution of biogeographic ancestry as described by both nuclear AIMs and male-specific non-recombinant Y chromosome markers is discussed for a sample of 173 Colombian individuals. The distribution of biogeographic ancestry (BGA) in this population includes ancestors from West Africa, America, and Western Europe. Although these individuals self-report ethnic identifications that are generally consistent with their BGA, the distribution of BGA among the ethnic groups shows a large degree of overlap which demonstrates the heterogeneous nature of these ethnic groups. Additionally, the Y-chromosomal markers, which are inherited exclusively through the male line can be traced to a likely geographic region of origin. The ancestry estimates from the nuclear and Y-chromosomal markers indicate that there is a bias towards more European males and more African and Indigenous American females contributing to the gene pool. This sex-biased gene flow is common in admixed populations of the Americas. In total, 515 individuals with mixed Indigenous American and European ancestry were genotyped for single nucleotide polymorphisms (SNPs) chosen to be ancestry informative between the European and Indigenous American parental populations. These SNPs were used to test for admixture linkage association between the candidate genes and variation in skin color. The results of this analysis show a novel association of the genes PAX3 and ASIP with mean constitutive skin pigmentation differences between European and Indigenous American populations. The roles of SLC24A5 and MATP (SLC45A2) in contributing to skin pigmentation differences between European and non-European populations were also confirmed. SLC24A5 and MATP (SLC45A2) are each linked to approximately 3 melanin units of variation in skin pigmentation while PAX3 and ASIP each contribute to less than 1.5 melanin units of difference.