The Pioneer Advantage: Filling the blank spots on the map of genome diversity in Europe

Documenting genome diversity is important for the local biomedical communities and instrumental in developing precision and personalized medicine. Currently, tens of thousands of whole-genome sequences from Europe are publicly available, but most of these represent populations of developed countries of Europe. The uneven distribution of the available data is further impaired by the lack of data sharing. Recent whole-genome studies in Eastern Europe, one in Ukraine and one in Russia, demonstrated that local genome diversity and population structure from Eastern Europe historically had not been fully represented. An unexpected wealth of genomic variation uncovered in these studies was not so much a consequence of high variation within their population, but rather due to the “pioneer advantage.” We discovered more variants because we were the first to prospect in the Eastern European genome pool. This simple comparison underscores the importance of removing the remaining geographic genome deserts from the rest of the world map of the human genome diversity

High levels of fluctuating asymmetry in populations of Apodemus flavicollis from the most contaminated areas in Chornobyl

Random deviations from the perfect symmetry of normally bilaterally symmetrical characters for an individual with a given genotype occur during individual development due to the influence of multiple environmental factors. Fluctuating asymmetry (FA) is often used as a measure of developmental instability, and can be estimated as the variance of the distribution of differences between the left and right sides. We addressed the question of whether levels of FA were elevated in radioactively contaminated populations living around Chornobyl compared to those in reference populations of the yellow-necked mouse (Apodemus flavicollis). In addition, we studied amounts of directional asymmetry (DA) when one side is larger than the other on average. There was a significant difference among populations, including reference populations, in the amount of both FA and DA. A higher level of FA was documented for the contaminated populations in close proximity to the failed Chornobyl reactor for both the asymmetry of size and shape. The FAs of size and shape were highest in populations from the most contaminated locations in the Chornobyl exclusion zone. Although the directional asymmetry of shape was also highest in the contaminated populations, it was not significantly different from those in most of the reference populations. Populations from less contaminated areas inside the Chornobyl exclusion zone did not express FA values different from those of the reference populations outside the affected area

Problems with developmental stability in two rodent species from Chornobyl

Changes in developmental patterns are some of the most important effects that may be observed at radioactively contaminated sites like those at Chornobyl. Developmental instability may arise from the interactions between an organism\u27s genotype and its environment and be manifested as deviant morphology. Fluctuating asymmetry (FA) is a measure of deviations from the expected bilateral symmetry of the body. Our objective was to test for differences in FA in two rodent species (Apodemus flavicollis and Clethrionomys glareolus) that live in habitats suirounding the failed Chornobyl reactor. Rodents were collected from four different locations (two contaminated and two reference sites), and a series of adult skulls were photographed and 24 landmarks on each skull were located on digital images from photographed skulls. FA was calculated from the differences in these landmarks on the right and left side of the skull. Significantly more asymmetry (~2X) was observed in mice and voles living around Chornobyl compared to those living at the uncontaminated reference sites. These are relatively large effects in comparison to those previously found for plants and swallows. FA can be a cheap, easily determined and sensitive indicator of radiation-induced stress in small mammals. FA can be used to prioritize environments for remediation efforts and to efficiently evaluate the effectiveness of the remediation efforts

Problems with developmental stability in two rodent species from Chornobyl

Changes in developmental patterns are some of the most important effects that may be observed at radioactively contaminated sites like those at Chornobyl. Developmental instability may arise from the interactions between an organism\u27s genotype and its environment and be manifested as deviant morphology. Fluctuating asymmetry (FA) is a measure of deviations from the expected bilateral symmetry of the body. Our objective was to test for differences in FA in two rodent species (Apodemus flavicollis and Clethrionomys glareolus) that live in habitats suirounding the failed Chornobyl reactor. Rodents were collected from four different locations (two contaminated and two reference sites), and a series of adult skulls were photographed and 24 landmarks on each skull were located on digital images from photographed skulls. FA was calculated from the differences in these landmarks on the right and left side of the skull. Significantly more asymmetry (~2X) was observed in mice and voles living around Chornobyl compared to those living at the uncontaminated reference sites. These are relatively large effects in comparison to those previously found for plants and swallows. FA can be a cheap, easily determined and sensitive indicator of radiation-induced stress in small mammals. FA can be used to prioritize environments for remediation efforts and to efficiently evaluate the effectiveness of the remediation efforts

Genome and gene alterations by insertions and deletions in the evolution of human and chimpanzee chromosome 22

<p>Abstract</p> <p>Background</p> <p>Understanding structure and function of human genome requires knowledge of genomes of our closest living relatives, the primates. Nucleotide insertions and deletions (indels) play a significant role in differentiation that underlies phenotypic differences between humans and chimpanzees. In this study, we evaluated distribution, evolutionary history, and function of indels found by comparing syntenic regions of the human and chimpanzee genomes.</p> <p>Results</p> <p>Specifically, we identified 6,279 indels of 10 bp or greater in a ~33 Mb alignment between human and chimpanzee chromosome 22. After the exclusion of those in repetitive DNA, 1,429 or 23% of indels still remained. This group was characterized according to the local or genome-wide repetitive nature, size, location relative to genes, and other genomic features. We defined three major classes of these indels, using local structure analysis: (i) those indels found uniquely without additional copies of indel sequence in the surrounding (10 Kb) region, (ii) those with at least one exact copy found nearby, and (iii) those with similar but not identical copies found locally. Among these classes, we encountered a high number of exactly repeated indel sequences, most likely due to recent duplications. Many of these indels (683 of 1,429) were in proximity of known human genes. Coding sequences and splice sites contained significantly fewer of these indels than expected from random expectations, suggesting that selection is a factor in limiting their persistence. A subset of indels from coding regions was experimentally validated and their impacts were predicted based on direct sequencing in several human populations as well as chimpanzees, bonobos, gorillas, and two subspecies of orangutans.</p> <p>Conclusion</p> <p>Our analysis demonstrates that while indels are distributed essentially randomly in intergenic and intronic genomic regions, they are significantly under-represented in coding sequences. There are substantial differences in representation of indel classes among genomic elements, most likely caused by differences in their evolutionary histories. Using local sequence context, we predicted origins and phylogenetic relationships of gene-impacting indels in primate species. These results suggest that genome plasticity is a major force behind speciation events separating the great ape lineages.</p

Reconstructing Native American Migrations from Whole-Genome and Whole-Exome Data

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern America ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations.Facultad de Ciencias Naturales y MuseoInstituto Multidisciplinario de Biología Celula

Reconstructing native American migrations from whole-genome and whole-exome data.

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations

Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles and Haplotypes: Evidence of Historical Selection in Africa

MYH9 was recently identified as renal susceptibility gene (OR 3–8, p<10−8) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (≥60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1 risk haplotype and the demographic and selective forces acting on the MYH9 region are not well explored. We reconstructed MYH9 haplotypes from 4 tagging single nucleotide polymorphisms (SNPs) spanning introns 12–23 using available data from HapMap Phase II, and by genotyping 938 DNAs from the Human Genome Diversity Panel (HGDP). The E-1 risk haplotype followed a cline, being most frequent within sub-Saharan African populations (range 50–80%), less frequent in populations from the Middle East (9–27%) and Europe (0–9%), and rare or absent in Asia, the Americas, and Oceania. The fixation indexes (FST) for pairwise comparisons between the risk haplotypes for continental populations were calculated for MYH9 haplotypes; FST ranged from 0.27–0.40 for Africa compared to other continental populations, possibly due to selection. Uniquely in Africa, the Yoruba population showed high frequency extended haplotype length around the core risk allele (C) compared to the alternative allele (T) at the same locus (rs4821481, iHs = 2.67), as well as high population differentiation (FST(CEU vs. YRI) = 0.51) in HapMap Phase II data, also observable only in the Yoruba population from HGDP (FST = 0.49), pointing to an instance of recent selection in the genomic region. The population-specific divergence in MYH9 risk allele frequencies among the world's populations may prove important in risk assessment and public health policies to mitigate the burden of kidney disease in vulnerable populations