Global Patterns of Diversity and Selection in Human Tyrosinase Gene

<div><p>Global variation in skin pigmentation is one of the most striking examples of environmental adaptation in humans. More than two hundred loci have been identified as candidate genes in model organisms and a few tens of these have been found to be significantly associated with human skin pigmentation in genome-wide association studies. However, the evolutionary history of different pigmentation genes is rather complex: some loci have been subjected to strong positive selection, while others evolved under the relaxation of functional constraints in low UV environment. Here we report the results of a global study of the human tyrosinase gene, which is one of the key enzymes in melanin production, to assess the role of its variation in the evolution of skin pigmentation differences among human populations. We observe a higher rate of non-synonymous polymorphisms in the European sample consistent with the relaxation of selective constraints. A similar pattern was previously observed in the <i>MC1R</i> gene and concurs with UV radiation-driven model of skin color evolution by which mutations leading to lower melanin levels and decreased photoprotection are subject to purifying selection at low latitudes while being tolerated or even favored at higher latitudes because they facilitate UV-dependent vitamin D production. Our coalescent date estimates suggest that the non-synonymous variants, which are frequent in Europe and North Africa, are recent and have emerged after the separation of East and West Eurasian populations.</p> </div

Median-joining network of <i>TYR</i> haplotypes.

<p>The network is based on the analysis of sequence data of the first haplotype block of 8634 bp length in 81 samples (162 chromosomes), color-coded by the geographic region of origin of the samples. Chimpanzee sequence (white circle) was used as an outgroup and chimpanzee specific variants have been excluded from the network output.</p

Ancestral recombination graph of <i>TYR</i> haplotypes.

<p>The tree is rooted by the chimpanzee sequence and presents recombination history of 942 worldwide samples (1884 chromosomes). Haplogroup frequency by populations is shown below the tree. Haplogroup names are shaded in yellow. Green arrows show the origin of recombination prefixes, blue arrows show the origin of recombination suffixes. Recombination points are shown by rectangles. Numerical superscript prefixes to the left of rs identifiers correspond to the relative physical position of SNPs. SNPs which were out of the range of our re-sequencing alignment are marked with superscript suffixes to the right of respective rs identifiers and correspond to the following phylogenetic equivalents in our re-sequencing data: A – rs12799137, B – rs7108676, C – rs12799347, D – rs12417632, E and F – rs5021654, G – rs7934747, H – rs1126809. Non-synonymous mutations or their phylogenetic equivalents are shown in red font with amino-acid substitutions specified. 95% confidence intervals for the detected haplogroup frequencies are given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074307#pone.0074307.s011" target="_blank">Table S6</a>.</p

Sliding window analysis of pairwise nucleotide differences in the 5’ flanking region of the <i>TYR</i> gene.

<p>Average estimates of pairwise differences (π) at exons, introns and the complete 5’ flanking region are provided for reference. Pairwise differences in six regional population groups are shown separately. Approximate locations of previously known regulatory elements (TDE, TPE and h5’URS) are marked with red diamonds. A newly identified region with decreased genetic variability is marked with a blue diamond. Position numbers are shown relative to the first codon of the <i>TYR</i> gene. Sliding window size is 1500 bp and step size is 375 bp.</p

Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective-2

<p><b>Copyright information:</b></p><p>Taken from "Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective"</p><p>http://www.biomedcentral.com/1471-2148/7/124</p><p>BMC Evolutionary Biology 2007;7():124-124.</p><p>Published online 27 Jul 2007</p><p>PMCID:PMC1976131.</p><p></p>PC. For details on populational datasets see Additional file . The codes in italic refer to the following populations: Morocco Arabs: [1,34], [33]; Morocco Berbers: [33], [34]; Algeria: [80], -Algerian Arabs [35]; Tunisia-[35], [7]; West Sahara: -Saharawis [33]; Egypt: [35], [7]; Sudan: [2]; Ethiopia: [2], -Oromo, -Amhara [5,7]; Kenya: -Kikiu & Kamba, -Maasai [7]; Uganda: -Ganda [7]; North Cameroon: -Podokwo, -Mandara [7], -Ouldeme, Daba [1,7,26], -Fali, Tali [1,26], -Fulbe [1,26]; South Cameroon: -Bassa, Ngoumba [7], -Bakaka, [1,7], -Bamileke [1,26], -Ewondo [1,26], -Bakola Pygmies [7]; CAR: -Biaka Pygmies [2,7]; DRC: -Nande, Herna [7]; -Mbuti Pygmies [2,7]; Guinea-Bissau: -Felupe-Djola, -Bijagós, - Balanta, -Papel, -Fulbe, -Mandenka, -Nalú (Present study); Burkina Faso: -Mossi [1,26], -Rimaibe [1,26], -Fulbe [1,26]; Gambia/Senegal: -Wolof [7], -Mandinka [7]; Mali: [2], -Dogon [7]; Ghana: -Fante [7]; Senegal: [5]; Namibia: -Herero, -Ambo [7], -!Kung, Sekele [1,7,26], -Tsumkwe San, Dama, Nama [7]; South Africa: -Sotho-Tswana, -Zulu, -Xhosa, -Shona [7], -Khoisan [2]. The PCA captures 87.0% of the variance with 74.0% and 13.0% attributed to the 1and 2PC, respectively. The 1PC reflects an axial proportion of E3a* vs. E1* where Papel and Felupe-Djola retain the higher proportions of the later. E3a* is again a main influence in the 2axis against that of R1b and E3b1, placing Mandenka apart from Bijagós and Fulbe

Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective-0

<p><b>Copyright information:</b></p><p>Taken from "Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective"</p><p>http://www.biomedcentral.com/1471-2148/7/124</p><p>BMC Evolutionary Biology 2007;7():124-124.</p><p>Published online 27 Jul 2007</p><p>PMCID:PMC1976131.</p><p></p>nclature and defining mutations assayed in this study, shown along the branches of the phylogeny, are as proposed by the YCC [60]. The bold link indicates the root, determined by comparisons with primates [2,79]

Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective-1

<p><b>Copyright information:</b></p><p>Taken from "Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective"</p><p>http://www.biomedcentral.com/1471-2148/7/124</p><p>BMC Evolutionary Biology 2007;7():124-124.</p><p>Published online 27 Jul 2007</p><p>PMCID:PMC1976131.</p><p></p>asets described in Additional files and

Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective-3

<p><b>Copyright information:</b></p><p>Taken from "Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective"</p><p>http://www.biomedcentral.com/1471-2148/7/124</p><p>BMC Evolutionary Biology 2007;7():124-124.</p><p>Published online 27 Jul 2007</p><p>PMCID:PMC1976131.</p><p></p>nclature and defining mutations assayed in this study, shown along the branches of the phylogeny, are as proposed by the YCC [60]. The bold link indicates the root, determined by comparisons with primates [2,79]

Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective-4

<p><b>Copyright information:</b></p><p>Taken from "Y-chromosomal diversity in the population of Guinea-Bissau: a multiethnic perspective"</p><p>http://www.biomedcentral.com/1471-2148/7/124</p><p>BMC Evolutionary Biology 2007;7():124-124.</p><p>Published online 27 Jul 2007</p><p>PMCID:PMC1976131.</p><p></p>asets described in Additional files and

First and second components of the Principal Component Analysis based on autosomal data.

<p>The corresponding colored dots for the Central Asian populations are shown on the lower right corner. The colored “arrows” on the background represent the frequency gradients as seen as on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076748#pone.0076748.s001" target="_blank">Figures S1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0076748#pone.0076748.s002" target="_blank">S2</a> and follow the same color code. It shall be stressed that they DO NOT represent actual gene flow, PCA analysis does not permit to reveal such movements. _Pak and _Afg stand for Pakistan and Afghanistan respectively.</p