New and Exciting in PLoS ONE

There are 42 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week - you go and look for your own favourites:

DNA from the Past Informs Ex Situ Conservation for the Future: An "Extinct" Species of Galápagos Tortoise Identified in Captivity:

Although not unusual to find captive relicts of species lost in the wild, rarely are presumed extinct species rediscovered outside of their native range. A recent study detected living descendents of an extinct Galápagos tortoise species (Chelonoidis elephantopus) once endemic to Floreana Island on the neighboring island of Isabela. This finding adds to the growing cryptic diversity detected among these species in the wild. There also exists a large number of Galápagos tortoises in captivity of ambiguous origin. The recently accumulated population-level haplotypic and genotypic data now available for C. elephantopus add a critical reference population to the existing database of 11 extant species for investigating the origin of captive individuals of unknown ancestry. We reanalyzed mitochondrial DNA control region haplotypes and microsatellite genotypes of 156 captive individuals using an expanded reference database that included all extant Galápagos tortoise species as well as the extinct species from Floreana. Nine individuals (six females and three males) exhibited strong signatures of Floreana ancestry and a high probability of assignment to C. elephantopus as detected by Bayesian assignment and clustering analyses of empirical and simulated data. One male with high assignment probability to C. elephantopus based on microsatellite genotypic data also possessed a "Floreana-like" mitochondrial DNA haplotype. Historical DNA analysis of museum specimens has provided critical spatial and temporal components to ecological, evolutionary, taxonomic and conservation-related research, but rarely has it informed ex situ species recovery efforts. Here, the availability of population-level genotypic data from the extinct C. elephantopus enabled the identification of nine Galápagos tortoise individuals of substantial conservation value that were previously misassigned to extant species of varying conservation status. As all captive individuals of C. elephantopus ancestry currently reside at a centralized breeding facility on Santa Cruz, these findings permit breeding efforts to commence in support of the reestablishment of this extinct species to its native range.

Cognitive and Motivational Requirements for the Emergence of Cooperation in a Rat Social Game:

Game theory and the Prisoner's Dilemma (PD) game in particular, which captures the paradox of cooperative interactions that lead to benefits but entail costs to the interacting individuals, have constituted a powerful tool in the study of the mechanisms of reciprocity. However, in non-human animals most tests of reciprocity in PD games have resulted in sustained defection strategies. As a consequence, it has been suggested that under such stringent conditions as the PD game humans alone have evolved the necessary cognitive abilities to engage in reciprocity, namely, numerical discrimination, memory and control of temporal discounting. We use an iterated PD game to test rats (Rattus norvegicus) for the presence of such cognitive abilities by manipulating the strategy of the opponent, Tit-for-Tat and Pseudo-Random, or the relative size of the temptation to defect. We found that rats shape their behaviour according to the opponent's strategy and the relative outcome resulting from cooperative or defective moves. Finally, we show that the behaviour of rats is contingent upon their motivational state (hungry versus sated). Here we show that rats understand the payoff matrix of the PD game and the strategy of the opponent. Importantly, our findings reveal that rats possess the necessary cognitive capacities for reciprocity-based cooperation to emerge in the context of a prisoner's dilemma. Finally, the validation of the rat as a model to study reciprocity-based cooperation during the PD game opens new avenues of research in experimental neuroscience.

A Neurosemantic Theory of Concrete Noun Representation Based on the Underlying Brain Codes:

This article describes the discovery of a set of biologically-driven semantic dimensions underlying the neural representation of concrete nouns, and then demonstrates how a resulting theory of noun representation can be used to identify simple thoughts through their fMRI patterns. We use factor analysis of fMRI brain imaging data to reveal the biological representation of individual concrete nouns like apple, in the absence of any pictorial stimuli. From this analysis emerge three main semantic factors underpinning the neural representation of nouns naming physical objects, which we label manipulation, shelter, and eating. Each factor is neurally represented in 3-4 different brain locations that correspond to a cortical network that co-activates in non-linguistic tasks, such as tool use pantomime for the manipulation factor. Several converging methods, such as the use of behavioral ratings of word meaning and text corpus characteristics, provide independent evidence of the centrality of these factors to the representations. The factors are then used with machine learning classifier techniques to show that the fMRI-measured brain representation of an individual concrete noun like apple can be identified with good accuracy from among 60 candidate words, using only the fMRI activity in the 16 locations associated with these factors. To further demonstrate the generativity of the proposed account, a theory-based model is developed to predict the brain activation patterns for words to which the algorithm has not been previously exposed. The methods, findings, and theory constitute a new approach of using brain activity for understanding how object concepts are represented in the mind.

Rapid Genomic Characterization of the Genus Vitis:

Next-generation sequencing technologies promise to dramatically accelerate the use of genetic information for crop improvement by facilitating the genetic mapping of agriculturally important phenotypes. The first step in optimizing the design of genetic mapping studies involves large-scale polymorphism discovery and a subsequent genome-wide assessment of the population structure and pattern of linkage disequilibrium (LD) in the species of interest. In the present study, we provide such an assessment for the grapevine (genus Vitis), the world's most economically important fruit crop. Reduced representation libraries (RRLs) from 17 grape DNA samples (10 cultivated V. vinifera and 7 wild Vitis species) were sequenced with sequencing-by-synthesis technology. We developed heuristic approaches for SNP calling, identified hundreds of thousands of SNPs and validated a subset of these SNPs on a 9K genotyping array. We demonstrate that the 9K SNP array provides sufficient resolution to distinguish among V. vinifera cultivars, between V. vinifera and wild Vitis species, and even among diverse wild Vitis species. We show that there is substantial sharing of polymorphism between V. vinifera and wild Vitis species and find that genetic relationships among V. vinifera cultivars agree well with their proposed geographic origins using principal components analysis (PCA). Levels of LD in the domesticated grapevine are low even at short ranges, but LD persists above background levels to 3 kb. While genotyping arrays are useful for assessing population structure and the decay of LD across large numbers of samples, we suggest that whole-genome sequencing will become the genotyping method of choice for genome-wide genetic mapping studies in high-diversity plant species. This study demonstrates that we can move quickly towards genome-wide studies of crop species using next-generation sequencing. Our study sets the stage for future work in other high diversity crop species, and provides a significant enhancement to current genetic resources available to the grapevine genetic community.

Mathematical Philology: Entropy Information in Refining Classical Texts' Reconstruction, and Early Philologists' Anticipation of Information Theory:

Philologists reconstructing ancient texts from variously miscopied manuscripts anticipated information theorists by centuries in conceptualizing information in terms of probability. An example is the editorial principle difficilior lectio potior (DLP): in choosing between otherwise acceptable alternative wordings in different manuscripts, "the more difficult reading [is] preferable." As philologists at least as early as Erasmus observed (and as information theory's version of the second law of thermodynamics would predict), scribal errors tend to replace less frequent and hence entropically more information-rich wordings with more frequent ones. Without measurements, it has been unclear how effectively DLP has been used in the reconstruction of texts, and how effectively it could be used. We analyze a case history of acknowledged editorial excellence that mimics an experiment: the reconstruction of Lucretius's De Rerum Natura, beginning with Lachmann's landmark 1850 edition based on the two oldest manuscripts then known. Treating words as characters in a code, and taking the occurrence frequencies of words from a current, more broadly based edition, we calculate the difference in entropy information between Lachmann's 756 pairs of grammatically acceptable alternatives. His choices average 0.26±0.20 bits higher in entropy information (95% confidence interval, P = 0.005), as against the single bit that determines the outcome of a coin toss, and the average 2.16±0.10 bits (95%) of (predominantly meaningless) entropy information if the rarer word had always been chosen. As a channel width, 0.26±0.20 bits/word corresponds to a 0.790.79+0.09â0.15 likelihood of the rarer word being the one accepted in the reference edition, which is consistent with the observed 547/756 = 0.72±0.03 (95%). Statistically informed application of DLP can recover substantial amounts of semantically meaningful entropy information from noise; hence the extension copiosior informatione lectio potior, "the reading richer in information [is] preferable." New applications of information theory promise continued refinement in the reconstruction of culturally fundamental texts.

Patterns of Urban Violent Injury: A Spatio-Temporal Analysis:

Injury related to violent acts is a problem in every society. Although some authors have examined the geography of violent crime, few have focused on the spatio-temporal patterns of violent injury and none have used an ambulance dataset to explore the spatial characteristics of injury. The purpose of this study was to describe the combined spatial and temporal characteristics of violent injury in a large urban centre. Using a geomatics framework and geographic information systems software, we studied 4,587 ambulance dispatches and 10,693 emergency room admissions for violent injury occurrences among adults (aged 18-64) in Toronto, Canada, during 2002 and 2004, using population-based datasets. We created kernel density and choropleth maps for 24-hour periods and four-hour daily time periods and compared location of ambulance dispatches and patient residences with local land use and socioeconomic characteristics. We used multivariate regressions to control for confounding factors. We found the locations of violent injury and the residence locations of those injured were both closely related to each other and clearly clustered in certain parts of the city characterised by high numbers of bars, social housing units, and homeless shelters, as well as lower household incomes. The night and early morning showed a distinctive peak in injuries and a shift in the location of injuries to a "nightlife" district. The locational pattern of patient residences remained unchanged during those times. Our results demonstrate that there is a distinctive spatio-temporal pattern in violent injury reflected in the ambulance data. People injured in this urban centre more commonly live in areas of social deprivation. During the day, locations of injury and locations of residences are similar. However, later at night, the injury location of highest density shifts to a "nightlife" district, whereas the residence locations of those most at risk of injury do not change.

Growth Rate Consequences of Coloniality in a Harmful Phytoplankter:

Allometric studies have shown that individual growth rate is inversely related to body size across a broad spectrum of organisms that vary greatly in size. Fewer studies have documented such patterns within species. No data exist directly documenting the influence of colony size on growth rate for microscopic, colonial organisms. To determine if similar negative relationships between growth rate and size hold for colonial organisms, we developed a technique for measuring the growth of individual colonies of a bloom-forming, toxic cyanobacterium, Microcystis aeruginosa using microscopy and digital image analysis. For five out of six genotypes of M. aeruginosa isolated from lakes in Michigan and Alabama, we found significant negative relationships between colony size and growth rate. We found large intraspecific variation in both the slope of these relationships and in the growth rate of colonies at a standard size. In addition, growth rate estimates for individual colonies were generally consistent with population growth rates measured using standard batch culture. Given that colony size varies widely within populations, our results imply that natural populations of colonial phytoplankton exist as a mosaic of individuals with widely varying ecological attributes (since size strongly affects growth rate, grazing mortality, and migration speed). Quantifying the influence of colony size on growth rate will permit development of more accurate, predictive models of ecological interactions (e.g., competition, herbivory) and their role in the proliferation of harmful algal blooms, in addition to increasing our understanding about why these interactions vary in strength within and across environments.

Sex Pheromone Receptor Specificity in the European Corn Borer Moth, Ostrinia nubilalis:

The European corn borer (ECB), Ostrinia nubilalis (Hubner), exists as two separate sex pheromone races. ECB(Z) females produce a 97:3 blend of Z11- and E11-tetradecenyl acetate whereas ECB(E) females produce an opposite 1:99 ratio of the Z and E isomers. Males of each race respond specifically to their conspecific female's blend. A closely related species, the Asian corn borer (ACB), O. furnacalis, uses a 3:2 blend of Z12- and E12-tetradecenyl acetate, and is believed to have evolved from an ECB-like ancestor. To further knowledge of the molecular mechanisms of pheromone detection and its evolution among closely related species we identified and characterized sex pheromone receptors from ECB(Z). Homology-dependent (degenerate PCR primers designed to conserved amino acid motifs) and homology-independent (pyrophosphate sequencing of antennal cDNA) approaches were used to identify candidate sex pheromone transcripts. Expression in male and female antennae was assayed by quantitative real-time PCR. Two-electrode voltage clamp electrophysiology was used to functionally characterize candidate receptors expressed in Xenopus oocytes. We characterized five sex pheromone receptors, OnOrs1 and 3-6. Their transcripts were 14-100 times more abundant in male compared to female antennae. OnOr6 was highly selective for Z11-tetradecenyl acetate (EC50 = 0.86±0.27 µM) and was at least three orders of magnitude less responsive to E11-tetradecenyl acetate. Surprisingly, OnOr1, 3 and 5 responded to all four pheromones tested (Z11- and E11-tetradecenyl acetate, and Z12- and E12-tetradecenyl acetate) and to Z9-tetradecenyl acetate, a behavioral antagonist. OnOr1 was selective for E12-tetradecenyl acetate based on an efficacy that was at least 5-fold greater compared to the other four components. This combination of specifically- and broadly-responsive pheromone receptors corresponds to published results of sensory neuron activity in vivo. Receptors broadly-responsive to a class of pheromone components may provide a mechanism for variation in the male moth response that enables population level shifts in pheromone blend use.

Microphthalmia in Texel Sheep Is Associated with a Missense Mutation in the Paired-Like Homeodomain 3 (PITX3) Gene:

Microphthalmia in sheep is an autosomal recessive inherited congenital anomaly found within the Texel breed. It is characterized by extremely small or absent eyes and affected lambs are absolutely blind. For the first time, we use a genome-wide ovine SNP array for positional cloning of a Mendelian trait in sheep. Genotyping 23 cases and 23 controls using Illumina's OvineSNP50 BeadChip allowed us to localize the causative mutation for microphthalmia to a 2.4 Mb interval on sheep chromosome 22 by association and homozygosity mapping. The PITX3 gene is located within this interval and encodes a homeodomain-containing transcription factor involved in vertebrate lens formation. An abnormal development of the lens vesicle was shown to be the primary event in ovine microphthalmia. Therefore, we considered PITX3 a positional and functional candidate gene. An ovine BAC clone was sequenced, and after full-length cDNA cloning the PITX3 gene was annotated. Here we show that the ovine microphthalmia phenotype is perfectly associated with a missense mutation (c.338G>C, p.R113P) in the evolutionary conserved homeodomain of PITX3. Selection against this candidate causative mutation can now be used to eliminate microphthalmia from Texel sheep in production systems. Furthermore, the identification of a naturally occurring PITX3 mutation offers the opportunity to use the Texel as a genetically characterized large animal model for human microphthalmia.

Heterologous Expression of Wheat VERNALIZATION 2 (TaVRN2) Gene in Arabidopsis Delays Flowering and Enhances Freezing Tolerance:

The vernalization gene 2 (VRN2), is a major flowering repressor in temperate cereals that is regulated by low temperature and photoperiod. Here we show that the gene from Triticum aestivum (TaVRN2) is also regulated by salt, heat shock, dehydration, wounding and abscissic acid. Promoter analysis indicates that TaVRN2 regulatory region possesses all the specific responsive elements to these stresses. This suggests pleiotropic effects of TaVRN2 in wheat development and adaptability to the environment. To test if TaVRN2 can act as a flowering repressor in species different from the temperate cereals, the gene was ectopically expressed in the model plant Arabidopsis. Transgenic plants showed no alteration in morphology, but their flowering time was significantly delayed compared to controls plants, indicating that TaVRN2, although having no ortholog in Brassicaceae, can act as a flowering repressor in these species. To identify the possible mechanism by which TaVRN2 gene delays flowering in Arabidopsis, the expression level of several genes involved in flowering time regulation was determined. The analysis indicates that the late flowering of the 35S::TaVRN2 plants was associated with a complex pattern of expression of the major flowering control genes, FCA, FLC, FT, FVE and SOC1. This suggests that heterologous expression of TaVRN2 in Arabidopsis can delay flowering by modulating several floral inductive pathways. Furthermore, transgenic plants showed higher freezing tolerance, likely due to the accumulation of CBF2, CBF3 and the COR genes. Overall, our data suggests that TaVRN2 gene could modulate a common regulator of the two interacting pathways that regulate flowering time and the induction of cold tolerance. The results also demonstrate that TaVRN2 could be used to manipulate flowering time and improve cold tolerance in other species.

Magnitude of Stratification in Human Populations and Impacts on Genome Wide Association Studies:

Genome-wide association studies (GWAS) may be biased by population stratification (PS). We conducted empirical quantification of the magnitude of PS among human populations and its impact on GWAS. Liver tissues were collected from 979, 59 and 49 Caucasian Americans (CA), African Americans (AA) and Hispanic Americans (HA), respectively, and genotyped using Illumina650Y (Ilmn650Y) arrays. RNA was also isolated and hybridized to Agilent whole-genome gene expression arrays. We propose a new method (i.e., hgdp-eigen) for detecting PS by projecting genotype vectors for each sample to the eigenvector space defined by the Human Genetic Diversity Panel (HGDP). Further, we conducted GWAS to map expression quantitative trait loci (eQTL) for the ~40,000 liver gene expression traits monitored by the Agilent arrays. HGDP-eigen performed similarly to the conventional self-eigen methods in capturing PS. However, leveraging the HGDP offered a significant advantage in revealing the origins, directions and magnitude of PS. Adjusting for eigenvectors had minor impacts on eQTL detection rates in CA. In contrast, for AA and HA, adjustment dramatically reduced association findings. At an FDR = 10%, we identified 65 eQTLs in AA with the unadjusted analysis, but only 18 eQTLs after the eigenvector adjustment. Strikingly, 55 out of the 65 unadjusted AA eQTLs were validated in CA, indicating that the adjustment procedure significantly reduced GWAS power. A number of the 55 AA eQTLs validated in CA overlapped with published disease associated SNPs. For example, rs646776 and rs10903129 have previously been associated with lipid levels and coronary heart disease risk, however, the rs10903129 eQTL was missed in the eigenvector adjusted analysis.


More like this

A week ago I pointed out that in some visualizations of world wide population variation South Asians & mestizos seem to overlap which each other to a great extent. The reason for this is that both populations can be modeled as admixtures between two separate, but related, populations. Mestizos…
There are 16 new articles in PLoS ONE today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Connotea, Stumbleupon, Facebook and Digg) with just one…
Kai Wang is a postdoctoral fellow at the Center for Applied Genomics, Children's Hospital of Philadelphia and an author on numerous genome-wide association studies. He left this lengthy comment as a response to my recent post on this comment by McClellan and King in Cell, and I felt it warranted…
The successes of genome-wide association studies (GWAS) in identifying genetic risk factors for common diseases have been heavily publicised in the mainstream media - barely a week goes by these days that we don't hear about another genome scan that has identified new risk genes for diabetes, lupus…