Gizakiaren aurpegiaren ezaugarri fenotipikoei loturiko aldakortasun genetikoaren analisia

Facial morphology is of great value for individual identification. In our project, we studied the geographical distribution of SNPs which influence facial morphology. Our PCA analysis shows that it is difficult to disentangle facial morphology from demographic history of mayor human populations. From PRS statistics we show that regarding nasal morphology, populations of East Asia and Africa seems to have a wider nose, whereas populations of Europe show a narrower nose. These results can be explained as a climatic adaptation. The investigation of facial morphology related SNPs can also be useful in forensic sciences; however, the phenotypic identification of morphological traits of an individual is complex and would require population-specific SNPs associated to anthropometric traits.; Aurpegiaren morfologia ezinbestekoa da banakoak euren artean ezberdindu ahal izateko. Lan honetan, aurpegiko ezaugarrietan eragina duten SNPak aztertu ditugu. Populazioen historia demografikoak aurpegiaren morfologiaren aldakortasunaren proportzio handia azaltzen duela aurkitzen dugu. Hala ere, aurpegiaren aldakortasunean hautespen sexuala bezalako beste faktore batzuek ere eragina izan dezakete, nahiz eta maila txikiagoan. Sudurraren morfologian arreta jarriz, Asia ekialdeko eta Afrikako populazioek sudur zabalagoa dute oro har, eta europarrek estuagoa. Bestalde, aurpegiaren ezaugarriei loturiko SNPen azterketa auzitegi-zientzietan ere erabilgarria izan daiteke, nahiz eta gaur egun DNAtik abiatuta banako baten identifikazio fenotipikoa konplexua den. Lan honen helburua da giza populazioak aurpegiaren morfologiari loturiko datu genetikoetatik (SNPak) abiatuta desberdintzea posible den egiaztatzea

Comparison of the transcriptional profiles of melanocytes from dark and light skinned individuals under basal conditions and following ultraviolet-b irradiation

We analysed the whole-genome transcriptional profile of 6 cell lines of dark melanocytes (DM) and 6 of light melanocytes (LM) at basal conditions and after ultraviolet-B (UVB) radiation at different time points to investigate the mechanisms by which melanocytes protect human skin from the damaging effects of UVB. Further, we assessed the effect of different keratinocyte-conditioned media (KCM+ and KCM-) on melanocytes. Our results suggest that an interaction between ribosomal proteins and the P53 signaling pathway may occur in response to UVB in both DM and LM. We also observed that DM and LM show differentially expressed genes after irradiation, in particular at the first 6h after UVB. These are mainly associated with inflammatory reactions, cell survival or melanoma. Furthermore, the culture with KCM+ compared with KCM- had a noticeable effect on LM. This effect includes the activation of various signaling pathways such as the mTOR pathway, involved in the regulation of cell metabolism, growth, proliferation and survival. Finally, the comparison of the transcriptional profiles between LM and DM under basal conditions, and the application of natural selection tests in human populations allowed us to support the significant evolutionary role of MIF and ATP6V0B in the pigmentary phenotype.Dept. Educacion, Universidades e Investigacion of the Basque Government IT542-10 BFI09.248 University of the Basque Country program UFI11/0

Complex signatures of selection for the melanogenic loci TYR, TYRP1 and DCT in humans

<p>Abstract</p> <p>Background</p> <p>The observed correlation between ultraviolet light incidence and skin color, together with the geographical apportionment of skin reflectance among human populations, suggests an adaptive value for the pigmentation of the human skin. We have used Affymetrix U133a v2.0 gene expression microarrays to investigate the expression profiles of a total of 9 melanocyte cell lines (5 from lightly pigmented donors and 4 from darkly pigmented donors) plus their respective unirradiated controls. In order to reveal signatures of selection in loci with a bearing on skin pigmentation in humans, we have resequenced between 4 to 5 kb of the proximal regulatory regions of three of the most differently expressed genes, in the expectation that variation at regulatory regions might account for intraespecific morphological diversity, as suggested elsewhere.</p> <p>Results</p> <p>Contrary to our expectations, expression profiles did not cluster the cells into unirradiated versus irradiated melanocytes, or into lightly pigmented versus darkly pigmented melanocytes. Instead, expression profiles correlated with the presence of Bovine Pituitary Extract (known to contain α-MSH) in the media. This allowed us to differentiate between melanocytes that are synthesizing melanin and those that are not. <it>TYR, TYRP1 </it>and <it>DCT </it>were among the five most differently expressed genes between these two groups. Population genetic analyses of sequence haplotypes of the proximal regulatory flanking-regions included Tajima's D, HEW and DHEW neutrality tests analysis. These were complemented with EHH tests (among others) in which the significance was obtained by a novel approach using extensive simulations under the coalescent model with recombination. We observe strong evidence for positive selection for <it>TYRP1 </it>alleles in Africans and for <it>DCT </it>and <it>TYRP1 </it>in Asians. However, the overall picture reflects a complex pattern of selection, which might include overdominance for <it>DCT </it>in Europeans.</p> <p>Conclusion</p> <p>Diversity patterns clearly evidence adaptive selection in pigmentation genes in Africans and Asians. In Europeans, the evidence is more complex, and both directional and balancing selection may be involved in light skin. As a result, different non-African populations may have acquired light skin by alternative ways, and so light skin, and perhaps dark skin too, may be the result of convergent evolution.</p

The Loss of Functional Caspase-12 in Europe Is a Pre-Neolithic Event

Contains fulltext : 109878.pdf (publisher's version ) (Open Access)BACKGROUND: Caspase-12 (CASP12) modulates the susceptibility to sepsis. In humans, the "C" allele at CASP12 rs497116 has been associated with an increased risk of sepsis. Instead, the derived "T" allele encodes for an inactive caspase-12. Interestingly, Eurasians are practically fixed for the inactive variant, whereas in Sub-Saharan Africa the active variant is still common (~24%). This marked structure has been explained as a function of the selective advantage that the inactive caspase-12 confers by increasing resistance to infection. As regards to both when positive selection started acting and as to the speed with which fixation was achieved in Eurasia, estimates depend on the method and assumptions used, and can vary substantially. Using experimental evidence, we propose that, least in Eurasia, the increase in the frequency of the T allele might be related to the selective pressure exerted by the increase in zoonotic diseases transmission caused by the interplay between increased human population densities and a closer contact with animals during the Neolithic. METHODOLOG/PRINCIPAL FINDINGS: We genotyped CASP12 rs497116 in prehistoric individuals from 6 archaeological sites from the North of the Iberian Peninsula that date from Late Upper Paleolithic to Late Neolithic. DNA extraction was done from teeth lacking cavities or breakages using standard anti-contamination procedures, including processing of the samples in a positive pressure, ancient DNA-only chamber, quantitation of DNAs by qPCR, duplication, replication, genotyping of associated animals, or cloning of PCR products. Out of 50, 24 prehistoric individuals could finally be genotyped for rs497116. Only the inactive form of CASP12 was found. CONCLUSIONS/SIGNIFICANCE: We demonstrate that the loss of caspase-12 in Europe predates animal domestication and that consequently CASP12 loss is unlikely to be related to the impact of zoonotic infections transmitted by livestock

La investigación en antropología física. Una mirada al futuro

Desde su creación en 1976 la Sociedad Española de Antropología Física (SEAF) viene celebrando sus congresos bienales de forma ininterrumpida en distintas ciudades españolas. Estos encuentros, destinados a la discusión de los avances y resultados de las investigaciones bioantropológicas, suponen un foro de debate científico en el que participan investigadores de diversas áreas interesados en los estudios de Antropología Física, promoviendo la interacción entre especialistas e investigadores en formación. Asimismo, y dado el interés que esta disciplina despierta en la sociedad en general, la celebración de los Congresos de la SEAF permite mostrar las novedades acontecidas en el ámbito de la ciencia bioantropológica, facilitando la difusión del conocimiento más allá de la esfera académica. En este marco de reuniones científicas, los profesores del área de Antropología Física de la Facultad de Ciencia y Tecnología de la Universidad del País Vasco-Euskal Herriko Unibertsitatea (UPV/EHU) han sido los encargados de organizar el XVIII Congreso de la SEAF, celebrado en Bilbao durante los días 19 a 21 de junio de 2013. Este libro recoge las ponencias y principales comunicaciones presentadas en el XVIII Congreso, seleccionadas para su publicación y agrupadas en diferentes bloques temáticos que recogen algunas de los conocimientos actuales de la investigación bioantropológica: Ecología Humana, Biología Esquelética y Antropología Forense Paleoantropología y Primatología, y Diversidad Genética Humana. Se ha pretendido mostrar algunas de las cuestiones más relevantes actualmente y la proyección futura de la investigación en Antropología biológica, encaminada tanto al cuestionamiento de paradigmas (como la preponderancia de África en la evolución humana o la existencia de una única especie humana a partir del Pleistoceno Superior, entre otros), como a la comprensión de la relación fenotipo-genotipo, entre otras cuestiones de gran importancia para la reconstrucción de la historia evolutiva de nuestra especie. Sirvan las ponencias invitadas como ejemplo del nuevo enfoque de algunas áreas de la investigación en Antropología

Association of TYR SNP rs1042602 with Melanoma Risk and Prognosis

Cutaneous melanoma is the most aggressive of skin tumors. In order to discover new biomarkers that could help us improve prognostic prediction in melanoma patients, we have searched for germline DNA variants associated with melanoma progression. Thus, after exome sequencing of a set of melanoma patients and healthy control individuals, we identified rs1042602, an SNP within TYR, as a good candidate. After genotyping rs1042602 in 1025 patients and 773 healthy donors, we found that the rs1042602-A allele was significantly associated with susceptibility to melanoma (CATT test: p = 0.0035). Interestingly, we also observed significant differences between patients with good and bad prognosis (5 years of follow-up) (n = 664) (CATT test for all samples p = 0.0384 and for men alone p = 0.0054). Disease-free-survival (DFS) analyses also showed that patients with the A allele had shorter DFS periods. In men, the association remained significant even in a multivariate Cox Proportional-hazards model, which was adjusted for age at diagnosis, Breslow thickness, ulceration and melanoma subtype (HR 0.4; 95% confidence interval (CI) 0.20–0.83; p = 0.0139). Based on our results, we propose that rs1042602-A is a risk allele for melanoma, which also seems to be responsible for a poorer prognosis of the disease, particularly in men

Simultaneous purifying selection on the ancestral MC1R allele and positive selection on the melanoma-risk allele V60L in South Europeans

In humans, the geographical apportionment of the coding diversity of the pigmentary locus melanocortin-1 receptor (MC1R) is, unusually, higher in Eurasians than in Africans. This atypical observation has been interpreted as the result of purifying selection due to functional constraint on MC1R in high UV-B radiation environments. By analyzing 3,142 human MC1R alleles from different regions of Spain in the context of additional haplotypic information from the 1000 Genomes (1000G) Project data, we show that purifying selection is also strong in southern Europe, but not so in northern Europe. Furthermore, we show that purifying and positive selection act simultaneously on MC1R. Thus, at least in Spain, regions at opposite ends of the incident UV-B radiation distribution show significantly different frequencies for the melanoma-risk allele V60L (a mutation also associated to red hair and fair skin and even blonde hair), with higher frequency of V60L at those regions of lower incident UV-B radiation. Besides, using the 1000G south European data, we show that the V60L haplogroup is also characterized by an extended haplotype homozygosity (EHH) pattern indicative of positive selection. We, thus, provide evidence for an adaptive value of human skin depigmentation in Europe and illustrate how an adaptive process can simultaneously help to maintain a disease-risk allele. In addition, our data support the hypothesis proposed by Jablonski and Chaplin (Human skin pigmentation as an adaptation to UVB radiation. Proc Natl Acad Sci U S A. 2010;107:8962-8968), which posits that habitation of middle latitudes involved the evolution of partially depigmented phenotypes that are still capable of suitable tanning.This works was supported by the former Spanish Ministerio de Ciencia e Innovación, project CGL2008-04066/BOS to S.A.; by the Dpt. Educacion, Universidades e Investigación of the Basque Government, project IT542-10; by program UFI11/09 by the University of the Basque Country, by "Programa de Investigacion Cientifica de la Universidad de La Laguna" (boc-a- 2010-255-7177), and by grants from the Health Institute “Carlos III” (FIS PI08/1383, FIS PI11/00623) to C.F. and co-financed by the European Regional Development Funds, “A way of making Europe” from the European Union. M.P.Y. was supported by a postdoctoral fellowship from Fundación Ramón Areces. We thank the Spanish Banco Nacional de AND (BNADN) (http://www.bancoadn.org/) for providing us with DNA samples from all over Spain. We also thank the Spanish Agencia Estatal de Meteorología (AEMET) (http://www.aemet.es/) for kindly providing us with the UV-B radiation data

The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population

We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans

Ancient DNA from Hunter-Gatherer and Farmer Groups from Northern Spain Supports a Random Dispersion Model for the Neolithic Expansion into Europe

Background/Principal Findings: The phenomenon of Neolithisation refers to the transition of prehistoric populations from a hunter-gatherer to an agro-pastoralist lifestyle. Traditionally, the spread of an agro-pastoralist economy into Europe has been framed within a dichotomy based either on an acculturation phenomenon or on a demic diffusion. However, the nature and speed of this transition is a matter of continuing scientific debate in archaeology, anthropology, and human population genetics. In the present study, we have analyzed the mitochondrial DNA diversity in hunter-gatherers and first farmers from Northern Spain, in relation to the debate surrounding the phenomenon of Neolithisation in Europe. Methodology/Significance: Analysis of mitochondrial DNA was carried out on 54 individuals from Upper Paleolithic and Early Neolithic, which were recovered from nine archaeological sites from Northern Spain (Basque Country, Navarre and Cantabria). In addition, to take all necessary precautions to avoid contamination, different authentication criteria were applied in this study, including: DNA quantification, cloning, duplication (51 % of the samples) and replication of the results (43 % of the samples) by two independent laboratories. Statistical and multivariate analyses of the mitochondrial variability suggest that the genetic influence of Neolithisation did not spread uniformly throughout Europe, producing heterogeneous genetic consequences in different geographical regions, rejecting the traditional models that explain the Neolithisation in Europe