Search

To assess the genetic affinities of extinct Ciboneys (also called Guanajuatabeys) from Cuba, 47 pre-Columbian skeletal samples belonging to this group were analyzed using ancient DNA techniques. At the time of European contact, the center and east of Cuba were occupied by agriculturalist Taino groups, while the west was mainly inhabited by Ciboneys, hunter-gatherers who have traditionally been considered a relic population descending from the initial colonization of the Caribbean. The mtDNA hypervariable region I (HVR-I) and haplogroup-specific markers were amplified and sequenced in 15 specimens using overlapping fragments; amplification from second extractions from the same sample, independent replication in different laboratories, and cloning of some PCR products support the authenticity of the sequences. Three of the five major mtDNA Amerindian lineages (A, C, and D) are present in the sample analyzed, in frequencies of 0.07, 0.60, and 0.33, respectively. Different phylogenetic analyses seem to suggest that the Caribbean most likely was populated from South America, although the data are still inconclusive, and Central American influences cannot be discarded. Our hypothesis is that the colonization of the Caribbean mainly took place in successive migration movements that emanated from the same area in South America, around the Lower Orinoco Valley: the first wave consisted of hunter-gatherer groups (ancestors of the Ciboneys), a subsequent wave of agriculturalists (ancestors of the Tainos), and a latter one of nomadic Carib warriors. However, further genetic studies are needed to confirm this scenario. KEY WORDS ancient DNA; HVRI sequences; migration; Antilles

The badger, Meles meles, is a widely distributed mustelid in Eurasia and shows large geographic variability in morphological characters whose evolutionary significance is unclear and needs to be contrasted with molecular data. We sequenced 512 bp of the mitochondrial DNA control region in 115 Eurasian badgers from 21 countries in order to test for the existence of structuring in their phylogeography, to describe the genetic relationships among their populations across its widespread geographic range, and to infer demographic and biogeographic processes. We found that the Eurasian badger is divided into four groups regarding their mitochondrial DNA: Europe, Southwest Asia, North and East Asia, and Japan. This result suggests that the separation of badgers into phylogeographic groups was influenced by cold Pleistocene glacial stages and permafrost boundaries in Eurasia, and by geographic barriers, such as mountains and deserts. Genetic variation within phylogeographic groups based on distances assuming the Tamura–Nei model with rate heterogeneity and invariable sites ( dT-N range: 3.3–4.2) was much lower than among them ( dT-N range: 10.7–38.0), and 80% of the variation could be attributed to differences among regions. Spatial analysis of molecular variance (samova), median-joining network, and Mantel test did not detect genetic structuring within any of the phylogeographic groups with the exception of Europe, where 50% of variation was explained by differences among groups of populations. Our data suggest that the European, Southwest Asian, and North and East Asian badgers evolved separately since the end of Pliocene, at the beginnings of glacial ages, whereas Japanese badgers separated from continental Asian badgers during the middle Pleistocene. Endangered badgers from Crete Island, classified as Meles meles arcalus subspecies, were closely related to badgers from Southwest Asia. We also detected sudden demographic growth in European and Southwest Asian badgers that occurred during the Middle Pleistocene. [ABSTRACT FROM AUTHOR]

Summary Phylogenetic analysis of mitochondrial DNA (mtDNA) performed in Western Mediterranean populations has shown that both shores share a common set of mtDNA haplogroups already found in Europe and the Middle East. Principal co-ordinates of genetic distances and principal components analyses based on the haplotype frequencies show that the main genetic difference is attributed to the higher frequency of sub-Saharan L haplogroups in NW Africa, showing some gene flow across the Sahara desert, with a major impact in the southern populations of NW Africa. The AMOVA demonstrates that SW European populations are highly homogeneous whereas NW African populations display a more heterogeneous genetic pattern, due to an east-west differentiation as a result of gene flow coming from the East. Despite the shared haplogroups found in both areas, the European V and the NW African U6 haplogroups reveal the traces of the Mediterranean Sea permeability to female migrations, and allowed for determination and quantification of the genetic contribution of both shores to the genetic landscape of the geographic area. Comparison of mtDNA data with autosomal markers and Y-chromosome lineages, analysed in the same populations, shows a congruent pattern, although female-mediated gene flow seems to have been more intense than male-mediated gene flow. [ABSTRACT FROM AUTHOR]

Discusses genome factors and population stratification involved in the structure of linkage disequilibrium in humans. Definition of recombination; Ways to characterize linkage disequilibrium; Description of the human genetic landscape; Impact of genetic history of humans on linkage disequilibrium.

Copyright of Annals of Human Biology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Forty-five dinucleotide short tandem repeat polymorphisms were typed in ten large samples of a globally distributed set of populations. Although these markers had been selected for high heterozygosity in European populations, we found them to be sufficiently informative for linkage analysis in non-Europeans. Heterozygosity, mean number of alleles, and mean number of private alleles followed a common trend: they were highest in the African samples, were somewhat lower in Europeans and East Asians, and were lowest in Amerindians. Genetic distances also reflected this pattern, and distances modelled after the stepwise mutation model yielded trees that were less in agreement with other genetic and archaeological evidence than distances based on differentiation by drift (FST). Genetic variation in non-Africans seems to be a subset of that in Africans, supporting the replacement hypothesis for the origin of modern humans. [ABSTRACT FROM AUTHOR]

Abstract Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD) have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America). The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe) on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total) communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD.

Abstract Background We address the problem of studying recombinational variations in (human) populations. In this paper, our focus is on one computational aspect of the general task: Given two networks G1 and G2, with both mutation and recombination events, defined on overlapping sets of extant units the objective is to compute a consensus network G3 with minimum number of additional recombinations. We describe a polynomial time algorithm with a guarantee that the number of computed new recombination events is within ϵ = sz(G1, G2) (function sz is a well-behaved function of the sizes and topologies of G1 and G2) of the optimal number of recombinations. To date, this is the best known result for a network consensus problem. Results Although the network consensus problem can be applied to a variety of domains, here we focus on structure of human populations. With our preliminary analysis on a segment of the human Chromosome X data we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. These results have been verified independently using traditional manual procedures. To the best of our knowledge, this is the first recombinations-based characterization of human populations. Conclusion We show that our mathematical model identifies recombination spots in the individual haplotypes; the aggregate of these spots over a set of haplotypes defines a recombinational landscape that has enough signal to detect continental as well as population divide based on a short segment of Chromosome X. In particular, we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. The agreement with mutation-based analysis can be viewed as an indirect validation of our results and the model. Since the model in principle gives us more information embedded in the networks, in our future work, we plan to investigate more non-traditional questions via these structures computed by our methodology.

Abstract Background Pathogens have represented an important selective force during the adaptation of modern human populations to changing social and other environmental conditions. The evolution of the immune system has therefore been influenced by these pressures. Genomic scans have revealed that immune system is one of the functions enriched with genes under adaptive selection. Results Here, we describe how the innate immune system has responded to these challenges, through the analysis of resequencing data for 132 innate immunity genes in two human populations. Results are interpreted in the context of the functional and interaction networks defined by these genes. Nucleotide diversity is lower in the adaptors and modulators functional classes, and is negatively correlated with the centrality of the proteins within the interaction network. We also produced a list of candidate genes under positive or balancing selection in each population detected by neutrality tests and showed that some functional classes are preferential targets for selection. Conclusions We found evidence that the role of each gene in the network conditions the capacity to evolve or their evolvability: genes at the core of the network are more constrained, while adaptation mostly occurred at particular positions at the network edges. Interestingly, the functional classes containing most of the genes with signatures of balancing selection are involved in autoinflammatory and autoimmune diseases, suggesting a counterbalance between the beneficial and deleterious effects of the immune response.

Abstract Background Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. Results We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.

Abstract Background The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene under human-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences. Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans, 20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39 worldwide human populations from the HGDP-CEPH diversity panel. Results The genome sequences recently available from other primate and non-primate species showed that FOXI1 divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant in Europeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsb statistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recent episode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on the putatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies strongly correlated with the absolute geographical latitude of the populations sampled. Conclusions We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate might be related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediated water-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

Abstract Background It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8. Results Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.