Gone with the currents: lack of genetic differentiation at the circum-continental scale in the Antarctic krill Euphausia superba

<p>Abstract</p> <p>Background</p> <p>Southern Ocean fauna represent a significant amount of global biodiversity, whose origin may be linked to glacial cycles determining local extinction/eradication with ice advance, survival of refugee populations and post-glacial re-colonization. This pattern implies high potential for differentiation in benthic shelf species with limited dispersal, yet consequences for pelagic organisms are less clear. The present study investigates levels of genetic variation and population structure of the Antarctic krill <it>Euphausia superba </it>using mitochondrial DNA and EST-linked microsatellite markers for an unprecedentedly comprehensive sampling of its populations over a circum-Antarctic range.</p> <p>Results</p> <p>MtDNA (ND1) sequences and EST-linked microsatellite markers indicated no clear sign of genetic structure among populations over large geographic scales, despite considerable power to detect differences inferred from forward-time simulations. Based on ND1, few instances of genetic heterogeneity, not significant after correction for multiple tests, were detected between geographic or temporal samples. Neutrality tests and mismatch distribution based on mtDNA sequences revealed strong evidence of past population expansion. Significant positive values of the parameter <it>g </it>(a measure of population growth) were obtained from microsatellite markers using a coalescent-based genealogical method and suggested a recent start (60 000 - 40 000 years ago) for the expansion.</p> <p>Conclusions</p> <p>The results provide evidence of lack of genetic heterogeneity of Antarctic krill at large geographic scales and unequivocal support for recent population expansion. Lack of genetic structuring likely reflects the tight link between krill and circum-Antarctic ocean currents and is consistent with the hypothesis that differentiation processes in Antarctic species are largely influenced by dispersal potential, whereas small-scale spatial and temporal differentiation might be due to local conditions leading to genetic patchiness. The signal of recent population growth suggests differential impact of glacial cycles on pelagic Antarctic species, which experienced population expansion during glaciations with increased available habitat, <it>versus </it>sedentary benthic shelf species.</p> <p>EST-linked microsatellites provide new perspectives to complement the results based on mtDNA and suggest that data-mining of EST libraries will be a useful approach to facilitate use of microsatellites for additional species.</p

Genetic Landscape of Slovenians: Past Admixture and Natural Selection Pattern

The Slovenian territory played a crucial role in the past serving as gateway for several human migrations. Previous studies used Slovenians as a source population to interpret different demographic events happened in Europe but not much is known about the genetic background and the demographic history of this population. Here, we analyzed genome-wide data from 96 individuals to shed light on the genetic role and history of the Slovenian population. Y chromosome diversity splits into two major haplogroups R1b and R1a with the latter suggesting a genetic contribution from the steppe. Slovenian individuals are more closely related to Northern and Eastern European populations than Southern European populations even though they are geographically closer. This pattern is confirmed by an admixture and clustering analysis. We also identified a single stream of admixture events between the Slovenians with Sardinians and Russians around 3c2630 BCE (2149-3112). Using ancient samples, we found a significant admixture in Slovenians using Yamnaya and the early Neolithic Hungarians as sources, dated around 3c1762 BCE (1099-2426) suggesting a strong contribution from the steppe to the foundation of the observed modern genetic diversity. Finally, we looked for signals of selection in candidate variants and we found significant hits in HERC2 and FADS responsible for blue eye color and synthesis of long-chain unsaturated fatty acids, respectively, when Slovenians were compared to Southern Europeans. While the comparison was done with Eastern Europeans, we identified significant signals in PKD2L1 and IL6R which are genes associated with taste and coronary artery disease, respectively

Changes in human effective population size overlap the beginning and end of a critical time in European medieval history, also characterized by the Black Death epidemic

The intersection of historiography and archaeology has long pondered over the impact of known historical events on census size. In recent times, genetic methods have successfully traced changes over time in the genetic size of a given population. Moreover, the correlation between genetic and census sizes of a population is contingent on several demographic assumptions that are relatively simple for our species. Our research endeavours to examine the changes in effective population size (Ne) in all human populations in the 1000 Genomes Project over the past two millennia. We compared our findings with estimates from historical censuses where available. Our investigation confirms what was already observed in France and reveals a common pattern found in most European populations, which manifests as a drastic population decrease beginning around the year 1300 and growth after the year 1600. This profile aligns well with known wars, famines, and epidemics that characterized these trying times in Europe. The most notable among them being the second plague epidemic, caused by Y. pestis, which in Europe commenced in 1347/8 and is also known as the "Black Death". Our findings demonstrate that changes in genetic population size through time can serve as a dependable proxy for census size, which is independent of potential biases in the written historical record. Consequently, we provide a robust estimate of the impact caused by the population crisis that followed the year 1300 on the European genomic landscape in light of previous results. Our study offers a new paradigm for interpreting the past and underscores the potential of genetic methods in reconstructing historical events

Establishment and equilibrium levels of deleterious mutations in large populations

Analytical and statistical stochastic approaches are used to model the dispersion of monogenic variants through large populations. These approaches are used to quantify the magnitude of the selective advantage of a monogenic heterozygous variant in the presence of a homozygous disadvantage. Dunbar’s results regarding the cognitive upper limit of the number of stable social relationships that humans can maintain are used to determine a realistic effective community size from which an individual can select mates. By envisaging human community structure as a network where social proximity rather than physical geography predominates, a significant simplification is achieved, implicitly accounting for the effects of migration and consanguinity, and with population structure and genetic drift becoming emergent features of the model. Effective community size has a dramatic effect on the probability of establishing beneficial alleles. It also affects the eventual equilibrium values that are reached in the case of variants conferring a heterozygous selective advantage, but a homozygous disadvantage, as in the case of cystic fibrosis and sickle cell disease. The magnitude of this selective advantage can then be estimated based on observed occurrence levels of a specific allele in a population, without requiring prior information regarding its phenotypic manifestation.http://www.nature.com/srep/index.htmlpm2020Electrical, Electronic and Computer EngineeringImmunologyMathematics and Applied Mathematic

Global diversity in the TAS2R38 bitter taste receptor: Revisiting a classic evolutionary PROPosal

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes

Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy

14noopenopenCini, Giulia; Mezzavilla, Massimo; Della Puppa, Lara; Cupelli, Elisa; Fornasin, Alessio; D'Elia, Angela Valentina; Dolcetti, Riccardo; Damante, Giuseppe; Bertok, Sara; Miolo, Gianmaria; Maestro, Roberta; de Paoli, Paolo; Amoroso, Antonio; Viel, AlessandraCini, Giulia; Mezzavilla, Massimo; Della Puppa, Lara; Cupelli, Elisa; Fornasin, Alessio; D'Elia, Angela Valentina; Dolcetti, Riccardo; Damante, Giuseppe; Bertok, Sara; Miolo, Gianmaria; Maestro, Roberta; de Paoli, Paolo; Amoroso, Antonio; Viel, Alessandr

Genetic Landscape of Slovenians: Past Admixture and Natural Selection Pattern

The Slovenian territory played a crucial role in the past serving as gateway for several human migrations. Previous studies used Slovenians as a source population to interpret different demographic events happened in Europe but not much is known about the genetic background and the demographic history of this population. Here, we analyzed genome-wide data from 96 individuals to shed light on the genetic role and history of the Slovenian population. Y chromosome diversity splits into two major haplogroups R1b and R1a with the latter suggesting a genetic contribution from the steppe. Slovenian individuals are more closely related to Northern and Eastern European populations than Southern European populations even though they are geographically closer. This pattern is confirmed by an admixture and clustering analysis. We also identified a single stream of admixture events between the Slovenians with Sardinians and Russians around ∼2630 BCE (2149-3112). Using ancient samples, we found a significant admixture in Slovenians using Yamnaya and the early Neolithic Hungarians as sources, dated around ∼1762 BCE (1099-2426) suggesting a strong contribution from the steppe to the foundation of the observed modern genetic diversity. Finally, we looked for signals of selection in candidate variants and we found significant hits in HERC2 and FADS responsible for blue eye color and synthesis of long-chain unsaturated fatty acids, respectively, when Slovenians were compared to Southern Europeans. While the comparison was done with Eastern Europeans, we identified significant signals in PKD2L1 and IL6R which are genes associated with taste and coronary artery disease, respectively

Genetic background of primary and familial HLH in Qatar: registry data and population study

BackgroundFamilial hemophagocytic lymphohistiocytosis (FHLH) is an inherited life-threatening disease. Five types are identified, with the addition of congenital immunodeficiency syndromes in which HLH is a typical manifestation. The literature on this disease is very scarce in the Middle East, with only a few scattered reports.MethodsWe report detailed demographic, clinical, and genomic data from 28 patients diagnosed with primary and familial HLH over the last decade in Qatar. An evaluation was performed of allele frequencies of deleterious variants from 12 primary and familial HLH causative genes on the Qatar Genome Programme (QGP) cohort of 14,669 Qatari individuals.ResultsThe genetic diagnosis was obtained in 15 patients, and four novel mutations in Perforin 1 (PRF1), UNC13D, LYST, and RAB27A genes were found. We identified 22,945 low/high/moderate/modifier impact variants significantly enriched in the QGP in those 12 genes. The variants rs1271079313 in PRF1 and rs753966933 in RAB27A found in our patient cohort were significantly more prevalent in the QGP compared to the Genome Aggregation Database (gnomAD) database, with a high carrier frequency in the Qatari population.ConclusionsWe established the first primary and familial HLH Registry in the Gulf Region and identified novel possibly pathogenic variants present at higher frequency in the Qatari population, which could be used for screening purposes. Raising awareness about primary and familial HLH and implementing screening activities in the Qatari highly inbred population could stem into more comprehensive premarital and prenatal evaluations and faster diagnosis

Enrichment of low-frequency functional variants revealed by whole-genome sequencing of multiple isolated European populations

The genetic features of isolated populations can boost power in complex-trait association studies, and an in-depth understanding of how their genetic variation has been shaped by their demographic history can help leverage these advantageous characteristics. Here, we perform a comprehensive investigation using 3,059 newly generated low-depth whole-genome sequences from eight European isolates and two matched general populations, together with published data from the 1000 Genomes Project and UK10K. Sequencing data give deeper and richer insights into population demography and genetic characteristics than genotype-chip data, distinguishing related populations more effectively and allowing their functional variants to be studied more fully. We demonstrate relaxation of purifying selection in the isolates, leading to enrichment of rare and low-frequency functional variants, using novel statistics, DVxy and SVxy. We also develop an isolation-index (Isx) that predicts the overall level of such key genetic characteristics and can thus help guide population choice in future complex-trait association studies.Peer reviewe