The legacy of domestication: accumulation of deleterious mutations in the dog genome

Dogs exhibit more phenotypic variation than any other mammal and are affected by a wide variety of genetic diseases. However, the origin and genetic basis of this variation is still poorly understood. We examined the effect of domestication on the dog genome by comparison with its wild ancestor, the gray wolf. We compared variation in dog and wolf genes using whole-genome single nucleotide polymorphism (SNP) data. The d(N)/d(S) ratio (omega) was around 50% greater for SNPs found in dogs than in wolves, indicating that a higher proportion of nonsynonymous alleles segregate in dogs compared with nonfunctional genetic variation. We suggest that the majority of these alleles are slightly deleterious and that two main factors may have contributed to their increase. The first is a relaxation of selective constraint due to a population bottleneck and altered breeding patterns accompanying domestication. The second is a reduction of effective population size at loci linked to those under positive selection due to Hill-Robertson interference. An increase in slightly deleterious genetic variation could contribute to the prevalence of disease in modern dog breeds.     

Bitter taste perception in Neanderthals through the analysis of the TAS2R38 gene

The bitter taste perception (associated with the ability or inability to taste phenylthiocarbamide) is mediated by the TAS2R38 gene. Most of the variation in this gene is explained by three common amino-acid polymorphisms at positions 49 (encoding proline or alanine), 262 (alanine or valine) and 296 (valine or isoleucine) that determine two common isoforms: proline–alanine–valine (PAV) and alanine–valine–isoleucine (AVI). PAV is the major taster haplotype (heterozygote and homozygote) and AVI is the major non-taster haplotype (homozygote). Amino acid 49 has the major effect on the distinction between tasters and non-tasters of all three variants. The sense of bitter taste protects us from ingesting toxic substances, present in some vegetables, that can affect the thyroid when ingested in large quantities. Balancing selection has been used to explain the current high non-taster frequency, by maintaining divergent TAS2R38 alleles in humans. We have amplified and sequenced the TAS2R38 amino acid 49 in the virtually uncontaminated Neanderthal sample of El Sidrón 1253 and have determined that it was heterozygous. Thus, this Neanderthal was a taster individual, although probably slightly less than a PAV homozygote. This indicates that variation in bitter taste perception pre-dates the divergence of the lineages leading to Neanderthals and modern humans.     

Paleogenomics in a Temperate Environment: Shotgun Sequencing from an Extinct Mediterranean Caprine

Background

Numerous endemic mammals, including dwarf elephants, goats, hippos and deers, evolved in isolation in the Mediterranean islands during the Pliocene and Pleistocene. Most of them subsequently became extinct during the Holocene. Recently developed high-throughput sequencing technologies could provide a unique tool for retrieving genomic data from these extinct species, making it possible to study their evolutionary history and the genetic bases underlying their particular, sometimes unique, adaptations.

Methodology/Principals Findings

A DNA extraction of a ∼6,000 year-old bone sample from an extinct caprine (Myotragus balearicus) from the Balearic Islands in the Western Mediterranean, has been subjected to shotgun sequencing with the GS FLX 454 platform. Only 0.27% of the resulting sequences, identified from alignments with the cow genome and comprising 15,832 nucleotides, with an average length of 60 nucleotides, proved to be endogenous.

Conclusions

A phylogenetic tree generated with Myotragus sequences and those from other artiodactyls displays an identical topology to that generated from mitochondrial DNA data. Despite being in an unfavourable thermal environment, which explains the low yield of endogenous sequences, our study demonstrates that it is possible to obtain genomic data from extinct species from temperate regions.     

The Effects of Immunostimulation Through Dietary Manipulation in the Rainbow Trout; Evaluation of Mucosal Immunity

Immunostimulant-containing diets are commonly used in aquaculture to enhance the resistance of cultured fish to disease and stress. Although widespread in use, there have been conflicting results published, and surprisingly little is known about the regulation of immune response-related genes in tissues key to mucosal immunity induced by immunostimulant dietary feeding. Using a salmonid-specific microarray platform enriched with immune-related genes and in situ hybridization, we investigated dietary acclimation in two organs relevant to mucosal immunity, the gills and the intestine, in the rainbow trout (Oncorhynchus mykiss). Immunostimulant diets significantly changed gene expression profiles and gene distribution in a tissue-specific manner: genes and functional Gene Ontology categories involved in immunity were differently expressed at portals of entry where significant changes in genes and functional groups related to remodeling processes and antigen presentation were observed. Furthermore, genes involved in chemotaxis, cell differentiation, antigen-presenting capacity and tissue remodeling were localized in both organs.     

The INTERPRET Decision-Support System version 3.0 for evaluation of Magnetic Resonance Spectroscopy data from human brain tumours and other abnormal brain masses

Background  

Proton Magnetic Resonance (MR) Spectroscopy (MRS) is a widely available technique for those clinical centres equipped with MR scanners. Unlike the rest of MR-based techniques, MRS yields not images but spectra of metabolites in the tissues. In pathological situations, the MRS profile changes and this has been particularly described for brain tumours. However, radiologists are frequently not familiar to the interpretation of MRS data and for this reason, the usefulness of decision-support systems (DSS) in MRS data analysis has been explored.     

SpectraClassifier 1.0: a user friendly,automated MRS-based classifier-development system

Background  

SpectraClassifier (SC) is a Java solution for designing and implementing Magnetic Resonance Spectroscopy (MRS)-based classifiers. The main goal of SC is to allow users with minimum background knowledge of multivariate statistics to perform a fully automated pattern recognition analysis. SC incorporates feature selection (greedy stepwise approach, either forward or backward), and feature extraction (PCA). Fisher Linear Discriminant Analysis is the method of choice for classification. Classifier evaluation is performed through various methods: display of the confusion matrix of the training and testing datasets; K-fold cross-validation, leave-one-out and bootstrapping as well as Receiver Operating Characteristic (ROC) curves.     

Wolf population genetics in Europe: a systematic review,meta‐analysis and suggestions for conservation and management

The grey wolf (Canis lupus) is an iconic large carnivore that has increasingly been recognized as an apex predator with intrinsic value and a keystone species. However, wolves have also long represented a primary source of human–carnivore conflict, which has led to long‐term persecution of wolves, resulting in a significant decrease in their numbers, genetic diversity and gene flow between populations. For more effective protection and management of wolf populations in Europe, robust scientific evidence is crucial. This review serves as an analytical summary of the main findings from wolf population genetic studies in Europe, covering major studies from the ‘pre‐genomic era’ and the first insights of the ‘genomics era’. We analyse, summarize and discuss findings derived from analyses of three compartments of the mammalian genome with different inheritance modes: maternal (mitochondrial DNA), paternal (Y chromosome) and biparental [autosomal microsatellites and single nucleotide polymorphisms (SNPs)]. To describe large‐scale trends and patterns of genetic variation in European wolf populations, we conducted a meta‐analysis based on the results of previous microsatellite studies and also included new data, covering all 19 European countries for which wolf genetic information is available: Norway, Sweden, Finland, Estonia, Latvia, Lithuania, Poland, Czech Republic, Slovakia, Germany, Belarus, Russia, Italy, Croatia, Bulgaria, Bosnia and Herzegovina, Greece, Spain and Portugal. We compared different indices of genetic diversity in wolf populations and found a significant spatial trend in heterozygosity across Europe from south‐west (lowest genetic diversity) to north‐east (highest). The range of spatial autocorrelation calculated on the basis of three characteristics of genetic diversity was 650?850 km, suggesting that the genetic diversity of a given wolf population can be influenced by populations up to 850 km away. As an important outcome of this synthesis, we discuss the most pressing issues threatening wolf populations in Europe, highlight important gaps in current knowledge, suggest solutions to overcome these limitations, and provide recommendations for science‐based wolf conservation and management at regional and Europe‐wide scales.