Genetic characteristics of the two main native groups in Bolivia : Aymaras and Quechuas

Deux populations appartenant aux groupes linguistiques principaux de la Bolivie, Aymaras et Quechuas, ont été étudiées par différent marqueurs génétiques pour fournir information sur leurs relations génétiques et processus démographiques qui pourraient avoir souffert pendant leur histoire. Ce travail comprend trois parties: l'étude i) de marqueurs génétiques autosomiques (insertions Alu), ii) uniparentaux, l'ADN mitochondrial (ADNmt) et le chromosome Y, et iii) d'une région du chromosome 19 avec le gene cluster des apolipoproteins APOE/C1/C4/C2. Dans le premier travail, trente-deux insertions Alu polymorphiques (PAIs), 18 autosomiques et 14 du chromosome X, ont été étudiées. L'objectif principal de l'étude était d'aborder les relations génétiques entre ces deux populations et d'éclaircir d'après ces données génétiques si l'expansion de la langue Quechua dans la Bolivie pouvait être attribuée à des processus démographiques (migrations Incas de parlants Quechua de Pérou vers la Bolivie) ou culturel (imposition de la langue Quechua par les Incas). La relation génétique très proche observée entre les deux populations boliviennes ainsi que leur différentiation des Quechuas du Pérou suggère que l'expansion de la langue Quechua dans la Bolivie eu lieu sans une contribution démographique importante. La deuxième partie concernant a été réalisé pour évaluer les possibles différences dépendant du genre et fournir plus de données pour éclaircir les processus démographiques de la région andine. Dans ce cas, les deux populations Boliviennes ont montré plus de différences génétiques pour l'ADNmt que pour le chromosome Y. Concernant l'ADNmt, les Aymaras semblent avoir été plus isolés au cours de leur histoire, fait qui aurait entrainé la conservation de certaines caractéristiques génétiques, tandis que les Quechuas aurait été plus perméables à l'incorporation des femmes étrangères et à l'influence péruvienne. Néanmoins, la mobilité des homes aurait été généralisée dans toute la région andine d'après l'homogénéité trouvée dans cette zone. L'étude d'une région autosomique d'environ 108kb incluant le groupe de gènes APOE/C1/C4/C2 et les régions adjacentes, dans laquelle, vingt-cinq polymorphismes (10 STRs et 15 SNPs) ont été analysés pour éclaircir l'histoire évolutive de cette région génomique dans les populations andines. Une partie de cette diversité réduite pourrait être attribuée à l'effet de la sélection qui pourrait être due à son importance physiologique, mais aussi du à leur histoires démographiques.Two populations belonging to the two main Native linguistic groups of Bolivia, Aymaras and Quechuas, have been analysed for different genetic markers in order to provide relevant information about their genetic relationships and demographic processes. This work comprises three parts: the study of i) autosomal markers (Alu insertions), ii) uniparental markers, both mtDNA and Y-chromosome, and iii) a region including the APOE/C1/C4/C2 gene cluster that code for apolipoproteins that can have epidemiological implications. In the first part, thirty-two polymorphic Alu insertions (18 autosomal and 14 from the X chromosome) were studied. The main objective was to determine from genetic data whether the expansion of the Quechua language into Bolivia could be associated with demographic (Inca migration of Quechua-speakers from Peru into Bolivia) or cultural (language imposition by the Inca Empire) processes. Our results indicated that the two Bolivian samples showed a high genetic similarity for both sets of markers and were clearly differentiated from the two Peruvian Quechua samples available in the literature. Additionally, our data were compared with the available literature to determine the genetic and linguistic structure, and East-West differentiation in South America. The close genetic relationship between the two Bolivian samples and their differentiation from the Quechua-speakers from Peru suggested that the Quechua language expansion in Bolivia took place without any important demographic contribution. The second part, mtDNA and Y-chromosome uniparental markers were studied to evaluate sex-speci?c differences and give new insights into the demographic processes of the Andean region. In that case, the two Bolivian samples showed more genetic differences for the mtDNA than for the Y-chromosome. For the mtDNA, 81% of Aymaras and 61% of Quechuas presented haplogroup B2. Native American Y-chromosomes were found in 97% of Aymaras (89% hg Q1a3a and 11% hgQ1a3*) and 78% of Quechuas (100% hg Q1a3a). Our data revealed high diversity values in the two populations, in agreement with other Andean studies. The comparisons with the available literature for both sets of markers indicated that the central Andean area is relatively homogeneous. For mtDNA, the Aymaras seemed to have been more isolated throughout time, maintaining their genetic characteristics, while the Quechuas have been more permeable to the incorporation of female foreigners and Peruvian influences. On the other hand, male mobility would have been widespread across the Andean region according to the homogeneity found in the area. Particular genetic characteristics presented by both samples support a past common origin of the Altiplano populations in the ancient Aymara territory, with independent, although related histories, with Peruvian (Quechuas) populations. The study of the autosomal region of 108kb, including the APOE/C1/C4/C2 gene cluster and the flanking region in which twenty five polymorphisms (10 STRs and 15 SNPs) were analysed to give new insights into the evolutionary history of this genomic region in Andean populations. In general, diversity in Bolivians was low, with nine out of 15 SNPs and seven out of 10 STRs being practically monomorphic. Part of this reduced diversity could be attributed to selection since the APOE/C1/C4/C2 region presented a high degree of conservation compared to the flanking genes in both Bolivians and Europeans, which may be due to its physiological importance. Also, the lower genetic diversity in Bolivians compared to Europeans for some markers could be attributed to their different demographic histories

Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR

Despite the interest in characterizing genomic variation, the presence of large repeats at the breakpoints hinders the analysis of many structural variants. This is especially problematic for inversions, since there is typically no gain or loss of DNA. Here, we tested novel linkage-based droplet digital PCR (ddPCR) assays to study 20 inversions ranging from 3.1 to 742 kb flanked by inverted repeats (IRs) up to 134 kb long. Of those, we validated 13 inversions predicted by different genome-wide techniques. In addition, we obtained new experimental human population information across 95 African, European, and East Asian individuals for 16 inversions, including four already validated variants without high-throughput genotyping methods. Through comparison with previous data, independent replicates and both inversion breakpoints, we demonstrate that the technique is highly accurate and reproducible. Most studied inversions are widespread across continents, and their frequency is negatively correlated with genetic length. Moreover, all except two show clear signs of being recurrent, and we could better define the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, the generated genotypes have allowed us to check inversion functional effects, validating gene expression differences reported before for two inversions and finding new candidate associations. Therefore, the developed methodology makes it possible to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications

Functional impact and evolution of a novel human polymorphic inversion that disrupts a gene and creates a fusion transcript

Since the discovery of chromosomal inversions almost 100 years ago, how they are maintained in natural populations has been a highly debated issue. One of the hypotheses is that inversion breakpoints could affect genes and modify gene expression levels, although evidence of this came only from laboratory mutants. In humans, a few inversions have been shown to associate with expression differences, but in all cases the molecular causes have remained elusive. Here, we have carried out a complete characterization of a new human polymorphic inversion and determined that it is specific to East Asian populations. In addition, we demonstrate that it disrupts the ZNF257 gene and, through the translocation of the first exon and regulatory sequences, creates a previously nonexistent fusion transcript, which together are associated to expression changes in several other genes. Finally, we investigate the potential evolutionary and phenotypic consequences of the inversion, and suggest that it is probably deleterious. This is therefore the first example of a natural polymorphic inversion that has position effects and creates a new chimeric gene, contributing to answer an old question in evolutionary biology

Uncovering adaptive evolution in the human lineage

Background: The recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution. Results: We compared human branch-specific substitutions with variation data in the current human population to measure the impact of adaptive evolution on human protein coding genes. The use of single nucleotide polymorphisms (SNPs) with high derived allele frequencies (DAFs) minimized the influence of segregating slightly deleterious mutations and improved the estimation of the number of adaptive sites. Using DAF ≥ 60% we showed that the proportion of adaptive substitutions is 0.2% in the complete gene set. However, the percentage rose to 40% when we focused on genes that are specifically accelerated in the human branch with respect to the chimpanzee branch, or on genes that show signatures of adaptive selection at the codon level by the maximum likelihood based branch-site test. In general, neural genes are enriched in positive selection signatures. Genes with multiple lines of evidence of positive selection include taxilin beta, which is involved in motor nerve regeneration and syntabulin, and is required for the formation of new presynaptic boutons. Conclusions: We combined several methods to detect adaptive evolution in human coding sequences at a genome-wide level. The use of variation data, in addition to sequence divergence information, uncovered previously undetected positive selection signatures in neural genes.This work was financially supported by the Ministerio de Economía y Competitividad from the Spanish Government (Plan Nacional project BFU2012-36820), and Institució Catalana de Recerca i Estudis Avançats (ICREA) from Generalitat de Cataluny

Uncovering adaptive evolution in the human lineage

Background: The recent increase in human polymorphism data, together with the availability of genome sequences from several primate species, provides an unprecedented opportunity to investigate how natural selection has shaped human evolution. Results: We compared human branch-specific substitutions with variation data in the current human population to measure the impact of adaptive evolution on human protein coding genes. The use of single nucleotide polymorphisms (SNPs) with high derived allele frequencies (DAFs) minimized the influence of segregating slightly deleterious mutations and improved the estimation of the number of adaptive sites. Using DAF ≥ 60% we showed that the proportion of adaptive substitutions is 0.2% in the complete gene set. However, the percentage rose to 40% when we focused on genes that are specifically accelerated in the human branch with respect to the chimpanzee branch, or on genes that show signatures of adaptive selection at the codon level by the maximum likelihood based branch-site test. In general, neural genes are enriched in positive selection signatures. Genes with multiple lines of evidence of positive selection include taxilin beta, which is involved in motor nerve regeneration and syntabulin, and is required for the formation of new presynaptic boutons. Conclusions: We combined several methods to detect adaptive evolution in human coding sequences at a genome-wide level. The use of variation data, in addition to sequence divergence information, uncovered previously undetected positive selection signatures in neural genes.This work was financially supported by the Ministerio de Economía y Competitividad from the Spanish Government (Plan Nacional project BFU2012-36820), and Institució Catalana de Recerca i Estudis Avançats (ICREA) from Generalitat de Cataluny

Oral microbiome homogeneity across diverse human groups from southern Africa: first results from southwestern Angola and Zimbabwe

Abstract Background While the human oral microbiome is known to play an important role in systemic health, its average composition and diversity patterns are still poorly understood. To gain better insights into the general composition of the microbiome on a global scale, the characterization of microbiomes from a broad range of populations, including non-industrialized societies, is needed. Here, we used the portion of non-human reads obtained through an expanded exome capture sequencing approach to characterize the saliva microbiomes of 52 individuals from eight ethnolinguistically diverse southern African populations from Angola (Kuvale, Kwepe, Himba, Tjimba, Kwisi, Twa, !Xun) and Zimbabwe (Tshwa), including foragers, food-producers, and peripatetic groups (low-status communities who provide services to their dominant neighbors). Results Our results indicate that neither host genetics nor livelihood seem to influence the oral microbiome profile, with Neisseria, Streptococcus, Prevotella, Rothia, and Porphyromonas being the five most frequent genera in southern African groups, in line with what has been shown for other human populations. However, we found that some Tshwa and Twa individuals display an enrichment of pathogenic genera from the Enterobacteriaceae family (i.e. Enterobacter, Citrobacter, Salmonella) of the Proteobacteria phylum, probably reflecting deficient sanitation and poor health conditions associated with social marginalization. Conclusions Taken together, our results suggest that socio-economic status, rather than ethnolinguistic affiliation or subsistence mode, is a key factor in shaping the salivary microbial profiles of human populations in southern Africa

Matriclans shape populations: Insights from the Angolan Namib Desert into the maternal genetic history of southern Africa

International audienc

Additional file 1 of Oral microbiome homogeneity across diverse human groups from southern Africa: first results from southwestern Angola and Zimbabwe

Supplementary Material

Additional file 2 of Oral microbiome homogeneity across diverse human groups from southern Africa: first results from southwestern Angola and Zimbabwe

Supplementary Material

Determining the impact of uncharacterized inversions in the human genome by droplet digital PCR

Despite the interest in characterizing genomic variation, the presence of large repeats at the breakpoints hinders the analysis of many structural variants. This is especially problematic for inversions, since there is typically no gain or loss of DNA. Here, we tested novel linkage-based droplet digital PCR (ddPCR) assays to study 20 inversions ranging from 3.1 to 742 kb flanked by inverted repeats (IRs) up to 134 kb long. Of those, we validated 13 inversions predicted by different genome-wide techniques. In addition, we obtained new experimental human population information across 95 African, European, and East Asian individuals for 16 inversions, including four already validated variants without high-throughput genotyping methods. Through comparison with previous data, independent replicates and both inversion breakpoints, we demonstrate that the technique is highly accurate and reproducible. Most studied inversions are widespread across continents, and their frequency is negatively correlated with genetic length. Moreover, all except two show clear signs of being recurrent, and we could better define the factors affecting recurrence levels and estimate the inversion rate across the genome. Finally, the generated genotypes have allowed us to check inversion functional effects, validating gene expression differences reported before for two inversions and finding new candidate associations. Therefore, the developed methodology makes it possible to screen these and other complex genomic variants quickly in a large number of samples for the first time, highlighting the importance of direct genotyping to assess their potential consequences and clinical implications