The genetic history of Europeans Pinhasi, Ron; Thomas, Mark G; Hofreiter, Michael ...
Trends in genetics,
10/2012, Volume:
28, Issue:
10
Journal Article
Peer reviewed
The evolutionary history of modern humans is characterized by numerous migrations driven by environmental change, population pressures, and cultural innovations. In Europe, the events most widely ...considered to have had a major impact on patterns of genetic diversity are the initial colonization of the continent by anatomically modern humans (AMH), the last glacial maximum, and the Neolithic transition. For some decades it was assumed that the geographical structuring of genetic diversity within Europe was mainly the result of gene flow during and soon after the Neolithic transition, but recent advances in next-generation sequencing (NGS) technologies, computer simulation modeling, and ancient DNA (aDNA) analyses are challenging this simplistic view. Here we review the current knowledge on the evolutionary history of humans in Europe based on archaeological and genetic data.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Abstract
C-type lectin-like receptor 2 (CLEC-2) is highly expressed on platelets and a subpopulation of myeloid cells, and is critical in lymphatic development. CLEC-2 has been shown to support ...thrombus formation at sites of inflammation, but to have a minor/negligible role in hemostasis. This identifies CLEC-2 as a promising therapeutic target in thromboinflammatory disorders, without hemostatic detriment. We utilized a GPIbα-Cre recombinase mouse for more restricted deletion of platelet-CLEC-2 than the previously used PF4-Cre mouse. clec1b
fl/fl
GPIbα-Cre
+
mice are born at a Mendelian ratio, with a mild reduction in platelet count, and present with reduced thrombus size post-FeCl
3
-induced thrombosis, compared to littermates. Antibody-mediated depletion of platelet count in C57BL/6 mice, to match clec1b
fl/fl
GPIbα-Cre
+
mice, revealed that the reduced thrombus size post-FeCl
3
-injury was due to the loss of CLEC-2, and not mild thrombocytopenia. Similarly, clec1b
fl/fl
GPIbα-Cre
+
mouse blood replenished with CLEC-2-deficient platelets
ex vivo
to match littermates had reduced aggregate formation when perfused over collagen at arterial flow rates. In contrast, platelet-rich thrombi formed following perfusion of human blood under flow conditions over collagen types I or III, atherosclerotic plaque, or inflammatory endothelial cells were unaltered in the presence of CLEC-2-blocking antibody, AYP1, or recombinant CLEC-2-Fc. The reduction in platelet aggregation observed in clec1b
fl/fl
GPIbα-Cre
+
mice during arterial thrombosis is mediated by the loss of CLEC-2 on mouse platelets. In contrast, CLEC-2 does not support thrombus generation on collagen, atherosclerotic plaque, or inflamed endothelial cells in human at arterial shear.
CRISPR-Cas9 technologies have transformed genome-editing of experimental organisms and have immense therapeutic potential. Despite significant advances in our understanding of the CRISPR-Cas9 system, ...concerns remain over the potential for off-target effects. Recent studies have addressed these concerns using whole-genome sequencing (WGS) of gene-edited embryos or animals to search for de novo mutations (DNMs), which may represent candidate changes introduced by poor editing fidelity. Critically, these studies used strain-matched, but not pedigree-matched controls and thus were unable to reliably distinguish generational or colony-related differences from true DNMs. Here we used a trio design and whole genome sequenced 8 parents and 19 embryos, where 10 of the embryos were mutagenised with well-characterised gRNAs targeting the coat colour Tyrosinase (Tyr) locus. Detailed analyses of these whole genome data allowed us to conclude that if CRISPR mutagenesis were causing SNV or indel off-target mutations in treated embryos, then the number of these mutations is not statistically distinguishable from the background rate of DNMs occurring due to other processes.
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Niche construction is the process by which organisms construct important components of their local environment in ways that introduce novel selection pressures. Lactase persistence is one of the ...clearest examples of niche construction in humans. Lactase is the enzyme responsible for the digestion of the milk sugar lactose and its production decreases after the weaning phase in most mammals, including most humans. Some humans, however, continue to produce lactase throughout adulthood, a trait known as lactase persistence. In European populations, a single mutation (−13910*T) explains the distribution of the phenotype, whereas several mutations are associated with it in Africa and the Middle East. Current estimates for the age of lactase persistence-associated alleles bracket those for the origins of animal domestication and the culturally transmitted practice of dairying. We report new data on the distribution of −13910*T and summarize genetic studies on the diversity of lactase persistence worldwide. We review relevant archaeological data and describe three simulation studies that have shed light on the evolution of this trait in Europe. These studies illustrate how genetic and archaeological information can be integrated to bring new insights to the origins and spread of lactase persistence. Finally, we discuss possible improvements to these models.
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Humans and their ancestors have traversed the Ethiopian landscape for millions of years, and present-day Ethiopians show great cultural, linguistic, and historical diversity, which makes them ...essential for understanding African variability and human origins. We genotyped 235 individuals from ten Ethiopian and two neighboring (South Sudanese and Somali) populations on an Illumina Omni 1M chip. Genotypes were compared with published data from several African and non-African populations. Principal-component and STRUCTURE-like analyses confirmed substantial genetic diversity both within and between populations, and revealed a match between genetic data and linguistic affiliation. Using comparisons with African and non-African reference samples in 40-SNP genomic windows, we identified “African” and “non-African” haplotypic components for each Ethiopian individual. The non-African component, which includes the SLC24A5 allele associated with light skin pigmentation in Europeans, may represent gene flow into Africa, which we estimate to have occurred ∼3 thousand years ago (kya). The non-African component was found to be more similar to populations inhabiting the Levant rather than the Arabian Peninsula, but the principal route for the expansion out of Africa ∼60 kya remains unresolved. Linkage-disequilibrium decay with genomic distance was less rapid in both the whole genome and the African component than in southern African samples, suggesting a less ancient history for Ethiopian populations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Adsorption and desorption of hydrogen from nanoporous materials, such as activated carbon, is usually fully reversible. We have prepared nanoporous metal-organic framework materials with flexible ...linkers in which the pore openings, as characterized in the static structures, appear to be too small to allow H2to pass. We observe hysteresis in their adsorption and desorption kinetics above the supercritical temperature of H2that reflects the dynamical opening of the "windows" between pores. This behavior would allow H2to be adsorbed at high pressures but stored at lower pressures.
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The Ari peoples of Ethiopia are comprised of different occupational groups that can be distinguished genetically, with Ari Cultivators and the socially marginalised Ari Blacksmiths recently shown to ...have a similar level of genetic differentiation between them (FST ≈ 0.023 - 0.04) as that observed among multiple ethnic groups sampled throughout Ethiopia. Anthropologists have proposed two competing theories to explain the origins of the Ari Blacksmiths as (i) remnants of a population that inhabited Ethiopia prior to the arrival of agriculturists (e.g. Cultivators), or (ii) relatively recently related to the Cultivators but presently marginalized in the community due to their trade. Two recent studies by different groups analysed genome-wide DNA from samples of Ari Blacksmiths and Cultivators and suggested that genetic patterns between the two groups were more consistent with model (i) and subsequent assimilation of the indigenous peoples into the expanding agriculturalist community. We analysed the same samples using approaches designed to attenuate signals of genetic differentiation that are attributable to allelic drift within a population. By doing so, we provide evidence that the genetic differences between Ari Blacksmiths and Cultivators can be entirely explained by bottleneck effects consistent with hypothesis (ii). This finding serves as both a cautionary tale about interpreting results from unsupervised clustering algorithms, and suggests that social constructions are contributing directly to genetic differentiation over a relatively short time period among previously genetically similar groups.
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Clear and simple as the truth Thomas, Francis-Noël; Turner, Mark
2017., 20170314, 2017, 2011-02-28, 2017-03-14, 20110101
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Everyone talks about style, but no one explains it. The authors of this book do; and in doing so, they provoke the reader to consider style, not as an elegant accessory of effective prose, but as its ...very heart.
At a time when writing skills have virtually disappeared, what can be done? If only people learned the principles of verbal correctness, the essential rules, wouldn't good prose simply fall into place? Thomas and Turner say no. Attending to rules of grammar, sense, and sentence structure will no more lead to effective prose than knowing the mechanics of a golf swing will lead to a hole-in-one. Furthermore, ten-step programs to better writing exacerbate the problem by failing to recognize, as Thomas and Turner point out, that there are many styles with different standards.
In the first half ofClear and Simple,the authors introduce a range of styles--reflexive, practical, plain, contemplative, romantic, prophetic, and others--contrasting them to classic style. Its principles are simple: The writer adopts the pose that the motive is truth, the purpose is presentation, the reader is an intellectual equal, and the occasion is informal. Classic style is at home in everything from business memos to personal letters, from magazine articles to university writing.
The second half of the book is a tour of examples--the exquisite and the execrable--showing what has worked and what hasn't. Classic prose is found everywhere: from Thomas Jefferson to Junichirō Tanizaki, from Mark Twain to the observations of an undergraduate. Here are many fine performances in classic style, each clear and simple as the truth.
Originally published in .
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The type VI secretion system (T6SS) is a multi-protein complex that injects bacterial effector proteins into target cells. It is composed of a cell membrane complex anchored to a contractile ...bacteriophage tail-like apparatus consisting of a sharpened tube that is ejected by the contraction of a sheath against a baseplate. We present structural and biochemical studies on TssA subunits from two different T6SSs that reveal radically different quaternary structures in comparison to the dodecameric E. coli TssA that arise from differences in their C-terminal sequences. Despite this, the different TssAs retain equivalent interactions with other components of the complex and position their highly conserved N-terminal ImpA_N domain at the same radius from the centre of the sheath as a result of their distinct domain architectures, which includes additional spacer domains and highly mobile interdomain linkers. Together, these variations allow these distinct TssAs to perform a similar function in the complex.
Invasive Haemophilus influenzae infection during pregnancy can cause preterm birth and fetal loss, but the mechanism is unclear. We investigated 54 cases of pregnancy-associated invasive H. ...influenzae disease in 52 unique pregnancies in the Auckland region of New Zealand during October 1, 2008‒September 30, 2018. Intraamniotic infection was identified in 36 (66.7%) of 54 cases. Outcome data were available for 48 pregnancies. Adverse pregnancy outcomes, defined as fetal loss, preterm birth, or the birth of an infant requiring intensive/special care unit admission, occurred in 45 (93.8%) of 48 (pregnancies. Fetal loss occurred in 17 (35.4%) of 48 pregnancies, before 24 weeks’ gestation in 13 cases, and at >24 weeks’ gestation in 4 cases. The overall incidence of pregnancy-associated invasive H. influenzae disease was 19.9 cases/100,000 births, which exceeded the reported incidence of pregnancy-associated listeriosis in New Zealand. We also observed higher rates in younger women and women of Māori ethnicity.
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