Human genetic differentiation across the Strait of Gibraltar

<p>Abstract</p> <p>Background</p> <p>The Strait of Gibraltar is a crucial area in the settlement history of modern humans because it represents a possible connection between Africa and Europe. So far, genetic data were inconclusive about the fact that this strait constitutes a barrier to gene flow, as previous results were highly variable depending on the genetic locus studied. The present study evaluates the impact of the Gibraltar region in reducing gene flow between populations from North-Western Africa and South-Western Europe, by comparing formally various genetic loci. First, we compute several statistics of population differentiation. Then, we use an original simulation approach in order to infer the most probable evolutionary scenario for the settlement of the area, taking into account the effects of both demography and natural selection at some loci.</p> <p>Results</p> <p>We show that the genetic patterns observed today in the region of the Strait of Gibraltar may reflect an ancient population genetic structure which has not been completely erased by more recent events such as Neolithic migrations. Moreover, the differences observed among the loci (i.e. a strong genetic boundary revealed by the Y-chromosome polymorphism and, at the other extreme, no genetic differentiation revealed by HLA-DRB1 variation) across the strait suggest specific evolutionary histories like sex-mediated migration and natural selection. By considering a model of balancing selection for HLA-DRB1, we here estimate a coefficient of selection of 2.2% for this locus (although weaker in Europe than in Africa), which is in line with what was estimated from synonymous versus non-synonymous substitution rates. Selection at this marker thus appears strong enough to leave a signature not only at the DNA level, but also at the population level where drift and migration processes were certainly relevant.</p> <p>Conclusions</p> <p>Our multi-loci approach using both descriptive analyses and Bayesian inferences lead to better characterize the role of the Strait of Gibraltar in the evolution of modern humans. We show that gene flow across the Strait of Gibraltar occurred at relatively high rates since pre-Neolithic times and that natural selection and sex-bias migrations distorted the demographic signal at some specific loci of our genome.</p

From hysteria to somatic symptom disorders: Searching for a common psychopathological ground

After decades of manifold contributions aimed at defining hysteria, somatisation and conversion, such syndromes are still neglected and their nosographical definition is debated. The DSM and the ICD have undergone major changes, but their clinical utility with regards to these syndromes is still questionable. On the contrary, the Diagnostic Criteria for Psychosomatic Research represents a useful clinical instrument since it translates psychosocial variables derived from psychosomatic research into operational tools. The present paper offers an overview on the psychopathological description of syndromes such as alexithymia, hypochondriasis, health anxiety, thanatophobia, conversion symptoms, anniversary and reaction which are frequent in clinical practice, but often misdiagnosed due to their absence in the DSM and the ICD. In addition, the influence of culture and cultural changes on the modifications of psychopathological manifestations is described as a further possible source of misdiagnosing and underreporting. New psychopathologies (e.g., multiple chemical sensitivity, orthorexia/vigorexia) that resemble conversion and/or somatisation have been developed, but neither is included in nosography nor taught to clinicians. The aim of the present paper is thus to describe psychopathological manifestations of somatic symptoms and related disorders to help clinicians formulate their diagnosis on the presence of signs and symptoms that can be elicited during a clinical visit, rather than by way of exclusion of other organic or psychiatric disease only

Arylamine N-Acetyltransferase 2 (NAT2) Genetic Diversity and Traditional Subsistence: A Worldwide Population Survey

Arylamine N-acetyltransferase 2 (NAT2) is involved in human physiological responses to a variety of xenobiotic compounds, including common therapeutic drugs and exogenous chemicals present in the diet and the environment. Many questions remain about the evolutionary mechanisms that have led to the high prevalence of slow acetylators in the human species. Evidence from recent surveys of NAT2 gene variation suggests that NAT2 slow-causing variants might have become targets of positive selection as a consequence of the shift in modes of subsistence and lifestyle in human populations in the last 10,000 years. We aimed to test more extensively the hypothesis that slow acetylation prevalence in humans is related to the subsistence strategy adopted by the past populations. To this end, published frequency data on the most relevant genetic variants of NAT2 were collected from 128 population samples (14,679 individuals) representing different subsistence modes and dietary habits, allowing a thorough analysis at both a worldwide and continent scale. A significantly higher prevalence of the slow acetylation phenotype was observed in populations practicing farming (45.4%) and herding (48.2%) as compared to populations mostly relying on hunting and gathering (22.4%) (P = 0.0007). This was closely mirrored by the frequency of the slow 590A variant that was found to occur at a three-fold higher frequency in food producers (25%) as compared to hunter-gatherers (8%). These findings are consistent with the hypothesis that the Neolithic transition to subsistence economies based on agricultural and pastoral resources modified the selective regime affecting the NAT2 acetylation pathway. Furthermore, the vast amount of data collected enabled us to provide a comprehensive and up-to-date description of NAT2 worldwide genetic diversity, thus building up a useful resource of frequency data for further studies interested in epidemiological or anthropological research questions involving NAT2

A homogenizing process of selection has maintained an \u27ultra-slow\u27 acetylation NAT2 variant in humans

N-acetyltransferase 2 (NAT2) is an important enzyme involved in the metabolism of a wide spectrum of naturally occurring xenobiotics, including therapeutic drugs and common environmental carcinogens. Extensive polymorphism in NAT2 gives rise to a wide interindividual variation in acetylation capacity which influences individual susceptibility to various drug-induced adverse reactions and cancers. Striking patterns of geographic differentiation have been described for the main slow acetylation variants of the NAT2 gene, suggesting the action of natural selection at this locus. In the present study, we took advantage of the whole-genome sequence data available from the 1000 Genomes project to investigate the global patterns of population genetic differentiation at NAT2 and determine whether they are atypical compared to the remaining variation of the genome. The non-synonymous substitution c.590G\u3eA (rs1799930) defining the slow NAT2*6 haplotype cluster exhibited an unusually low FST value when compared to the genome average (FST = 0.006, P-value = 0.016). It was pointed out as the most likely target of a homogenizing process of selection promoting the same allelic variant in globally distributed populations. The rs1799930 A allele has been associated with the slowest acetylation capacity in vivo and its substantial correlation with the subsistence strategy adopted by past human populations suggests that it may have conferred a selective advantage in populations shifting from foraging to agricultural and pastoral activities in the Neolithic period. Results of neutrality tests further supported an adaptive evolution of the NAT2 gene through either balancing selection or directional selection acting on multiple standing slow-causing variants

Mutual visibility by luminous robots without collisions

We consider the Mutual Visibility problem for anonymous dimensionless robots with obstructed visibility moving in a plane: starting from distinct locations, the robots must reach, without colliding, a configuration where no three of them are collinear. We study this problem in the luminous robots model, in which each robot has a visible light that can assume colors from a fixed set. Among other results, we prove that Mutual Visibility can be solved in SSynch with 2 colors and in ASynch with 3 colors. If an adversary can interrupt and stop a robot moving to its computed destination, Mutual Visibility is still solvable in SSynch with 3 colors and, if the robots agree on the direction of one axis, also in ASynch. As a byproduct, we provide the first obstructed-visibility solutions to two classical problems for oblivious robots: collision-less convergence to a point (also known as near-gathering) and circle formation