The beneficial substitution of an allele shapes patterns of genetic variation at linked sites. Thus, in principle, adaptations can be mapped by looking for the signature of directional selection in ...polymorphism data. In practice, such efforts are hampered by the need for an accurate characterization of the demographic history of the species and of the effects of positive selection. In an attempt to circumvent these difficulties, researchers are increasingly taking a purely empirical approach, in which a large number of genomic regions are ordered by summaries of the polymorphism data, and loci with extreme values are considered to be likely targets of positive selection. We evaluated the reliability of the "empirical" approach, focusing on applications to human data and to maize. To do so, we considered a coalescent model of directional selection in a sensible demographic setting, allowing for selection on standing variation as well as on a new mutation. Our simulations suggest that while empirical approaches will identify several interesting candidates, they will also miss many--in some cases, most--loci of interest. The extent of the trade-off depends on the mode of positive selection and the demographic history of the population. Specifically, the false-discovery rate is higher when directional selection involves a recessive rather than a co-dominant allele, when it acts on a previously neutral rather than a new allele, and when the population has experienced a population bottleneck rather than maintained a constant size. One implication of these results is that, insofar as attributes of the beneficial mutation (e.g., the dominance coefficient) affect the power to detect targets of selection, genomic scans will yield an unrepresentative subset of loci that contribute to adaptations.
Rice is a facultative short-day plant, and molecular genetic studies have identified the major genes involved in short-day flowering. However, the molecular mechanisms promoting the diversity of ...flowering time in cultivated rice are not known. We used a core collection of 64 rice cultivars that represent the genetic diversity of 332 accessions from around the world and studied the expression levels and polymorphisms of 6 genes in the short-day flowering pathway. The RNA levels of Heading date 3a (Hd3a), encoding a floral activator, are highly correlated with flowering time, and there is a high degree of polymorphism in the Heading date 1 (Hd1) protein, which is a major regulator of Hd3a expression. Functional and nonfunctional alleles of Hd1 are associated with early and late flowering, respectively, suggesting that Hd1 is a major determinant of variation in flowering time of cultivated rice. We also found that the type of Hd3a promoter and the level of Ehd1 expression contribute to the diversity in flowering time and Hd3a expression level. We evaluated the contributions of these 3 factors by a statistical analysis using a simple linear model, and the results supported our experimental observations.
The current generation of ground-based imaging atmospheric Cherenkov telescopes (IACTs) operate in the very-high-energy (VHE) domain from ~100 GeV to ~100 TeV. They use electronic digital trigger ...systems to discern the Cherenkov light flashes emitted by extensive air showers (EASs), from the overwhelming light of the night sky (LoNS) background. Near the telescope energy threshold, the number of emitted Cherenkov photons by gamma-ray-induced EASs is comparable to the fluctuations of the LoNS and the photon distribution at the Cherenkov-imaging camera plane becomes patchy. This results in a severe loss of effectiveness of the digital triggers based on combinatorial logic of thresholded signals. A stereoscopic analog trigger system has been developed for improving the detection capabilities of the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes at the lowest energies. It is based on the analog sum of the photosensor electrical signals. In this article, the architectural design, technical performances, and configuration of this stereoscopic analog trigger, dubbed " Sum-Trigger-II ," are described.
ST8SIA2 is an important molecule regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of the ST8SIA2 gene is considered to be protective against schizophrenia ...by conferring tolerance to psychosocial stress. Here, we examined the promoter-type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them. In AMHs, the TCT-type, showing the second lowest promoter activity, was most prevalent in the ancestral population of non-Africans. However, the detection of only the CGT-type from AH samples and recombination tracts in AH sequences showed that the CGT- and TGT-types, exhibiting the two highest promoter activities, were common in AH populations. Furthermore, interspecies gene flow occurred into AMHs from AHs and into Denisovans from Neanderthals, influencing promoter-type compositions independently in both AMHs and AHs. The difference of promoter-type composition makes PPA unique in each population. East and Southeast Asian populations show the lowest PPA. This results from the selective increase of the CGC-type, showing the lowest promoter activity, in these populations. Every non-African population shows significantly lower PPA than African populations, resulting from the TCT-type having the highest prevalence in the ancestral population of non-Africans. In addition, PPA reduction is also found among subpopulations within Africa via a slight increase of the TCT-type. These findings indicate a trend toward lower PPA in the spread of AMHs, interpreted as a continuous adaptation to psychosocial stress arising in migration. This trend is considered as genetic tuning for the evolution of collective brains. The inferred promoter-type composition of AHs differed markedly from that of AMHs, resulting in higher PPA in AHs than in AMHs. This suggests that the trend toward lower PPA is a unique feature in AMH spread.
As corals in tropical regions are threatened by increasing water temperatures, poleward range expansion of reef-building corals has been observed, and temperate regions are expected to serve as ...refugia in the face of climate change. To elucidate the important indicators of the sustainability of coral populations, we examined the genetic diversity and connectivity of the common reef-building coral Acropora hyacinthus along the Kuroshio Current, including recently expanded (<50 years) populations. Among the three cryptic lineages found, only one was distributed in temperate regions, which could indicate the presence of Kuroshio-associated larval dispersal barriers between temperate and subtropical regions, as shown by oceanographic simulations as well as differences in environmental factors. The level of genetic diversity gradually decreased towards the edge of the species distribution. This study provides an example of the reduced genetic diversity in recently expanded marginal populations, thus indicating the possible vulnerability of these populations to environmental changes. This finding underpins the importance of assessing the genetic diversity of newly colonized populations associated with climate change for conservation purposes. In addition, this study highlights the importance of pre-existing temperate regions as coral refugia, which has been rather underappreciated in local coastal management.
Single nucleotide polymorphism (SNP) data are widely used in research on natural populations. Although they are useful, SNP genotyping data are known to contain bias, normally referred to as ...ascertainment bias, because they are conditioned by already confirmed variants. This bias is introduced during the genotyping process, including the selection of populations for novel SNP discovery and the number of individuals involved in the discovery panel and selection of SNP markers. It is widely recognized that ascertainment bias can cause inaccurate inferences in population genetics and several methods to address these bias issues have been proposed. However, especially in natural populations, it is not always possible to apply an ideal ascertainment scheme because natural populations tend to have complex structures and histories. In addition, it was not fully assessed if ascertainment bias has the same effect on different types of population structure. Here we examine the effects of bias produced during the selection of population for SNP discovery and consequent SNP marker selection processes under three demographic models: the island, stepping-stone, and population split models. Results show that site frequency spectra and summary statistics contain biases that depend on the joint effect of population structure and ascertainment schemes. Additionally, population structure inferences are also affected by ascertainment bias. Based on these results, it is recommended to evaluate the validity of the ascertainment strategy prior to the actual typing process because the direction and extent of ascertainment bias vary depending on several factors.
The two MAGIC imaging atmospheric Cherenkov telescopes (IACTs) are located on the Canary island of La Palma. Their cameras are currently equipped with more than 1000 photomultiplier tubes (PMTs). We ...developed a silicon photomultiplier (SiPM) based detector module to evaluate the feasibility of a camera upgrade using only solid state detectors. We combined SiPMs to a composite matrix in order to achieve the same active area as the 1inch PMTs currently in use. This first prototype was installed in 2015 and is operated alongside the PMTs. Utilizing the collected data, we developed two more SiPM based detector modules. They are equipped with SiPMs from two different suppliers. These three different SiPM based detector modules will enable us to compare three different manufacturers of SiPMs under real observational conditions. Most important is the comparison to the neighbouring PMT modules.
•The performance expectations at high levels of background light are IACTs described.•The operational stability of DC and temperature is presented.•A calibration procedure for gain and cross talk is demonstrated.•A comparison to PMTs is shown utilizing the described calibration method.
What evolutionary forces shape genes that contribute to the risk of human disease? Do similar selective pressures act on alleles that underlie simple versus complex disorders
1–3? Answers to these ...questions will shed light onto the origin of human disorders (e.g.,
4) and help to predict the population frequencies of alleles that contribute to disease risk, with important implications for the efficient design of mapping studies
5–7. As a first step toward addressing these questions, we created a hand-curated version of the Mendelian Inheritance in Man database (OMIM). We then examined selective pressures on Mendelian-disease genes, genes that contribute to complex-disease risk, and genes known to be essential in mouse by analyzing patterns of human polymorphism and of divergence between human and rhesus macaque. We found that Mendelian-disease genes appear to be under widespread purifying selection, especially when the disease mutations are dominant (rather than recessive). In contrast, the class of genes that influence complex-disease risk shows little signs of evolutionary conservation, possibly because this category includes targets of both purifying and positive selection.
Most models of positive directional selection assume codominance of the beneficial allele. We examine the importance of this assumption by implementing a coalescent model of positive directional ...selection with arbitrary dominance. We find that, for a given mean fixation time, a beneficial allele has a much weaker effect on diversity at linked neutral sites when the allele is recessive.
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