Search

Background: Sex-biased dispersal is widespread among mammals, including the brown bear (Ursus arctos). Previous phylogeographic studies of the brown bear based on maternally inherited mitochondrial DNA have shown intraspecific genetic structuring around the northern hemisphere. The brown bears on Hokkaido Island, northern Japan, comprise three distinct maternal lineages that presumably immigrated to the island from the continent in three different periods. Here, we investigate the paternal genetic structure across northeastern Asia and assess the connectivity among and within intraspecific populations in terms of male-mediated gene flow. Results: We analyzed paternally inherited Y-chromosomal DNA sequence data and Y-linked microsatellite data of 124 brown bears from Hokkaido, the southern Kuril Islands (Kunashiri and Etorofu), Sakhalin, and continental Eurasia (Kamchatka Peninsula, Ural Mountains, European Russia, and Tibet). The Hokkaido brown bear population is paternally differentiated from, and lacked recent genetic connectivity with, the continental Eurasian and North American populations. We detected weak spatial genetic structuring of the paternal lineages on Hokkaido, which may have arisen through male-mediated gene flow among natal populations. In addition, our results suggest that the different dispersal patterns between male and female brown bears, combined with the founder effect and subsequent genetic drift, contributed to the makeup of the Etorofu Island population, in which the maternal and paternal lineages show different origins. Conclusions: Brown bears on Hokkaido and the adjacent southern Kuril Islands experienced different maternal and paternal evolutionary histories. Our results indicate that sex-biased dispersal has played a significant role in the evolutionary history of the brown bear in continental populations and in peripheral insular populations, such as on Hokkaido, the southern Kuril Islands, and Sakhalin. [ABSTRACT FROM AUTHOR]

The Xist gene produces a long noncoding RNA that initiates chromosomewide gene repression on the inactive X chromosome in female mammals. Recent progress has advanced the understanding of Xist function at the molecular level. This review provides an overview of insights from genetic approaches and puts the new data in the context of an emerging mechanistic model as well as the existing literature. Some consideration is given on how independent biochemical studies on X inactivation help to advance on the wider question of chromatin regulation in the mammalian dosage compensation system. [ABSTRACT FROM AUTHOR]

Viral sequence integration into the mammalian genome has long been perceived as a health risk. In some cases, integration translates to chronic viral infection, and in other instances, oncogenic gene mutations occur. However, research also shows that animal cells can benefit from integrated viral sequences (e.g., to support host cell development or to silence foreign invaders). Here we propose that, comparable with the clustered regularly interspaced short palindromic repeats that provide bacteria with adaptive immunity against invasive bacteriophages, animal cells may co-opt integrated viral sequences to support immune memory. We hypothesize that host cells express viral peptides from open reading frames in integrated sequences to boost adaptive B cell and T cell responses long after replicating viruses are cleared. In support of this hypothesis, we examine previous literature describing (1) viruses that infect acutely (e.g., vaccinia viruses and orthomyxoviruses) followed by unexplained, long-term persistence of viral nucleotide sequences, viral peptides, and virus-specific adaptive immunity, (2) the high frequency of endogenous viral genetic elements found in animal genomes, and (3) mechanisms with which animal host machinery supports foreign sequence integration. [ABSTRACT FROM AUTHOR]

Animal mitochondrial genome harbours 13 protein coding genes which regulate the process of respiration. The mitochondrial NADH dehydrogenase 1 (MT-ND1) gene, one of the 13 protein-coding genes, encodes the NADH dehydrogenase 1 enzyme of the respiratory chain. Analysis of codon usage bias (CUB) acquires importance for better understanding of the molecular biology, new gene discovery, design of transgenes and gene evolution. The MT-ND1 gene seems to be a good candidate for analyzing codon usage pattern, since no work has yet been reported. Moreover, it is still not clear which factors significantly influence the codon usage pattern. In the present study, comparative analysis of codon usage pattern, expression level and influencing factors for MT-ND1 gene from 100 different species each of pisces, aves and mammals were used for CUB analysis. Our result suggests that the gene is AT rich in pisces, aves and mammals and most of the nucleotides significantly differ among them as revealed from t -test. CUB was not remarkable as reflected by high value of effective number of codons and it also significantly differs among pisces, aves and mammals. Although we found that CUB is mainly influenced by natural selection and mutation pressure for MT-ND1 gene as suggested by correlation and correspondence analysis but neutrality plot further revealed that natural selection played a major role and mutation pressure played a minor role in codon usage pattern. Additionally, t -test analysis showed that the MT-ND1 gene has a wide significant discrepancy in codon choices in pisces, aves and mammals. This study has contributed to boost our understanding about the mechanism of distribution of the codons and the factors that may influence the evolution of the MT-ND1 gene. [ABSTRACT FROM AUTHOR]

The field of ancient DNA (aDNA) has recently been in a state of exponential growth, largely driven by the uptake of Next Generation Sequencing (NGS) techniques. Much of this work has focused on the mammalian megafauna and ancient humans, with comparatively less studies looking at micromammal fauna, despite the potential of these species in testing evolutionary, environmental and taxonomic theories. Several factors make micromammal fauna ideally suited for aDNA extraction and sequencing. Micromammal subfossil assemblages often include the large number of individuals appropriate for population level analyses, and, furthermore, the assemblages are frequently found in cave sites where the constant temperature and sheltered environment provide favourable conditions for DNA preservation. This review looks at studies that include the use of aDNA in molecular analysis of micromammal fauna, in order to examine the wide array of questions that can be answered in the study of small mammals using new palaeogenetic techniques. This study highlights the bias in current aDNA studies and assesses the future use of aDNA as a tool for the study of micromammal fauna. [ABSTRACT FROM AUTHOR]

This study reports on extensive experimental material covering more than 30 years of studying the genetics of mole voles. Sex chromosomes of Ellobius demonstrate an extraordinary case of mammalian sex chromosomes evolution. Five species of mole voles own three types of sex chromosomes; typical for placentals: XY♂/XX♀; and atypical X0♂/X0♀; or XX♂/XX♀. Mechanisms of sex determination in all Ellobius species remain enigmatic. It was supposed that the Y chromosome was lost twice and independently in subgenera Bramus and Ellobius. Previous to the Y being lost, the X chromosome in distinct species obtained some parts of the Y chromosome, with or without Sry, and accumulated one or several copies of the Eif2s3y gene. Along with enormous variations of sex chromosomes, genes of sex determination pathway and autosomes, and five mole vole species demonstrate ability to establish different meiotic mechanisms, which stabilize their genetic systems and make it possible to overcome the evolutionary deadlocks. [ABSTRACT FROM AUTHOR]

Interactions between conspecifics early in life have the potential to shape phenotypic differences between individuals. These changes in phenotype may subsequently be passed to future offspring, something that has been studied in live-bearing mammals where there is often an element of parental care. The present study considers the transgenerational effects of social environment in zebrafish, Danio rerio , an egg-laying animal that shows no parental care, thus removing any influence of parental interaction and allowing the effects of conspecific interaction to be clearly determined. Zebrafish (F 0 ) were reared from fertilization to reproduction in three different social treatments: isolation, groups of 30 or groups of 100. At 28 days post fertilization, individuals were tested for anxiety and activity and at 3 months old for aggression. These F 0 fish were raised to sexual maturity and bred within their treatment group. The F 1 generation were then raised in groups of 30, irrespective of parental social environment and were assessed for behaviour in the same way as their parents. Social isolation increased anxiety and decreased aggression in the F 0 fish compared to those raised in social groups of 100. F 0 fish raised in social groups of 30 showed an intermediate response. Differences in anxiety were not passed to the F 1 generation; however, offspring of socially isolated fish were less aggressive than offspring of parents from social groups of 30 and 100. The social environment that an individual experienced from fertilization to reproduction affected their own behaviour and the behaviour of their offspring. [ABSTRACT FROM AUTHOR]

Background: Leishmania is a protozoan parasite that alternates its life cycle between the sand-fly vector and the mammalian host. This alternation involves environmental changes and leads the parasite to dynamic modifications in morphology, metabolism, cellular signaling and regulation of gene expression to allow for a rapid adaptation to new conditions. The L-arginine pathway in L. amazonensis is important during the parasite life cycle and interferes in the establishment and maintenance of the infection in mammalian macrophages. Host arginase is an immune-regulatory enzyme that can reduce the production of nitric oxide by activated macrophages, directing the availability of L-arginine to the polyamine pathway, resulting in parasite replication. In this work, we performed transcriptional profiling to identify differentially expressed genes in L. amazonensis wild-type (La-WT) versus L. amazonensis arginase knockout (La-arg-) promastigotes and axenic amastigotes. Methodology/Principal findings: A total of 8253 transcripts were identified in La-WT and La-arg- promastigotes and axenic amastigotes, about 60% of them codifying hypothetical proteins and 443 novel transcripts, which did not match any previously annotated genes. Our RNA-seq data revealed that 85% of genes were constitutively expressed. The comparison of transcriptome and metabolome data showed lower levels of arginase and higher levels of glutamate-5-kinase in La-WT axenic amastigotes compared to promastigotes. The absence of arginase activity in promastigotes increased the levels of pyrroline 5-carboxylate reductase, but decreased the levels of arginosuccinate synthase, pyrroline 5-carboxylate dehydrogenase, acetylornithine deacetylase and spermidine synthase transcripts levels. These observations can explain previous metabolomic data pointing to the increase of L-arginine, citrulline and L-glutamate and reduction of aspartate, proline, ornithine and putrescine. Altogether, these results indicate that arginase activity is important in Leishmania gene expression modulation during differentiation and adaptation to environmental changes. Here, we confirmed this hypothesis with the identification of differential gene expression of the enzymes involved in biosynthesis of amino acids, arginine and proline metabolism and arginine biosynthesis. Conclusions/Significance: All data provided information about the transcriptomic profiling and the expression levels of La-WT and La-arg- promastigotes and axenic amastigotes. These findings revealed the importance of arginase in parasite survival and differentiation, and indicated the existence of a coordinated response in the absence of arginase activity related to arginine and polyamine pathways. [ABSTRACT FROM AUTHOR]

Background: Pre-mRNA splicing is the removal of introns from precursor mRNAs (pre-mRNAs) and the concurrent ligation of the flanking exons to generate mature mRNA. This process is catalyzed by the spliceosome, where the splicing factor 1 (SF1) specifically recognizes the seven-nucleotide branch point sequence (BPS) and the U2 snRNP later displaces the SF1 and binds to the BPS. In mammals, the degeneracy of BPS motifs together with the lack of a large set of experimentally verified BPSs complicates the task of BPS prediction in silico. Results: In this paper, we develop a simple and yet efficient heuristic model for human BPS prediction based on a novel scoring scheme, which quantifies the splicing strength of putative BPSs. The candidate BPS is restricted exclusively within a defined BPS search region to avoid the influences of other elements in the intron and therefore the prediction accuracy is improved. Moreover, using two types of relative frequencies for human BPS prediction, we demonstrate our model outperformed other current implementations on experimentally verified human introns. Conclusion: We propose that the binding energy contributes to the molecular recognition involved in human pre-mRNA splicing. In addition, a genome-wide human BPS prediction is carried out. The characteristics of predicted BPSs are in accordance with experimentally verified human BPSs, and branch site positions relative to the 3'ss and the 5'end of the shortened AGEZ are consistent with the results of published papers. Meanwhile, a webserver for BPS predictor is freely available at http://biocomputer.bio.cuhk.edu.hk/BPS. [ABSTRACT FROM AUTHOR]

The vertebrate-specific ESCC microRNA family arises from two genetic loci in mammals: miR-290/miR-371 and miR-302. The miR-302 locus is found broadly among vertebrates, whereas the miR-290/miR-371 locus is unique to eutheria, suggesting a role in placental development. Here, we evaluate that role. A knock-in reporter for the mouse miR-290 cluster is expressed throughout the embryo until gastrulation, when it becomes specifically expressed in extraembryonic tissues and the germline. In the placenta, expression is limited to the trophoblast lineage, where it remains highly expressed until birth. Deletion of the miR-290 cluster gene (Mirc5) results in reduced trophoblast progenitor cell proliferation and a reduced DNA content in endoreduplicating trophoblast giant cells. The resulting placenta is reduced in size. In addition, the vascular labyrinth is disorganized, with thickening of the maternal-fetal blood barrier and an associated reduction in diffusion. Multiple mRNA targets of the miR-290 cluster microRNAs are upregulated. These data uncover a crucial function for the miR-290 cluster in the regulation of a network of genes required for placental development, suggesting a central role for these microRNAs in the evolution of placental mammals. [ABSTRACT FROM AUTHOR]

The aim of this study was to estimate the heritability of semen freezability and to estimate the genetic correlation between frozen-thawed sperm traits and the growth rate in a paternal rabbit line. Estimated heritabilities showed that frozen-thawed semen traits are heritable (ranged between 0.08 and 0.15). In the case of Live-FT (percentage of viable sperm after freezing), the estimated heritability is the highest one, and suggests the possibility of effective selection. After the study of genetic correlations it seems that daily weight gain (DG) was negatively correlated with sperm freezability, but no further conclusions could be drawn due to the high HPD95%. More data should be included in order to obtain better accuracy for the estimates of these genetic correlations. If the results obtained at present study were confirmed, it would imply that selection for DG could alter sperm cell membranes or seminal plasma composition, both components related to sperm cryoresistance. [ABSTRACT FROM AUTHOR]

Mammalian cell lines are characterized by a complex and flexible metabolism. A single model that could describe the variations in metabolic behavior triggered by variations in the culture conditions would be a precious tool in bioprocess development. In this paper, we introduce an approach to generate a poly-pathway model and use it to simulate diverse metabolic states triggered in response to removal, reduction or doubling of amino acids in the culture medium of an antibody-producing CHO cell line. Macro-reactions were obtained from a metabolic network via elementary flux mode enumeration and the fluxes were modeled by kinetic equations with saturation and inhibition effects from external medium components. Importantly, one set of kinetic parameters was estimated using experimental data of the multiple metabolic states. A good fit between the model and the data was obtained for the majority of the metabolites and the experimentally observed flux variations. We find that the poly-pathway modeling approach is promising for the simulation of multiple metabolic states. [ABSTRACT FROM AUTHOR]

The CRISPR/Cas9 system provides a powerful method for the genetic manipulation of the mammalian genome, allowing knockout of individual genes as well as the generation of genome-wide knockout cell libraries for genetic screening. However, the diploid status of most mammalian cells restricts the application of CRISPR/Cas9 in genetic screening. Mammalian haploid embryonic stem cells (haESCs) have only one set of chromosomes per cell, avoiding the issue of heterozygous recessive mutations in diploid cells. Thus, the combination of haESCs and CRISPR/Cas9 facilitates the generation of genome-wide knockout cell libraries for genetic screening. Here, we review recent progress in CRISPR/Cas9 and haPSCs and discuss their applications in genetic screening. [ABSTRACT FROM AUTHOR]

Game species like the red deer have been subjected to anthropogenic impacts for centuries. Translocations are often carried out-sometimes illegally-not only for sporting purposes, but also to increase trophy quality, reduce inbreeding, or mitigate bottlenecks after excessive persecution. Apart from the blurring of large-scale genetic structure, translocations without adequate quarantine measure risk introducing pathogens into potentially immunologically naïve populations. It is therefore important to understand the frequency of clandestine translocations. Identification of non-autochthonous animals and their potential origin is often difficult and, in red deer, has been hampered by the lack of large-scale genotypic datasets for comparison. In the present study, we make use of a recently published European-wide microsatellite dataset to detect and quantify the presence of non-autochthonous red deer in a large population sample ( n = 1,780) from Central Europe (Belgium). Using factorial correspondence analysis, assignment tests and Bayesian clustering algorithms we arrive at an estimate of 3.7% non-autochthonous animals (or their descendants). Some of these animals were assigned to a nearby French population and may have immigrated into Belgium naturally, but the large majority must have been introduced by humans. Our analysis pointed to the British Isles and Germany/Poland as the potential origin of many introduced deer, regions known to have been source populations for translocations in Europe and beyond. We found evidence for recreational hunters using carcasses from farmed deer to fulfill mandatory hunting quotas. Our study is the first to quantify the extent of human-mediated introductions in a European game species at such a large scale with large and representative sample sizes. [ABSTRACT FROM AUTHOR]

The evolutionary processes that shape patterns of diversity in highly mobile marine species are poorly understood, but important towards transferable inference on their effective conservation. In this study, bottlenose dolphins ( Tursiops sp.) are studied to address this broader question. They exhibit remarkable geographical variation for morphology, life history, and genetic diversity, and this high level of variation has made the taxonomy of the genus controversial. A significant population structure has been reported for the most widely distributed species, the common bottlenose dolphin ( T. truncatus), in almost all ocean basins, though no data have been available for the western North Pacific Ocean (WNP). The genetic diversity of bottlenose dolphins in the WNP was investigated based on 20 microsatellite and one mitochondrial DNA markers for samples collected from Taiwanese, Japanese, and Philippine waters (9°-39°N, 120°-140°E) during 1986-2012. The results indicated that there are at least four genetically differentiated populations of common bottlenose dolphins in the western and central North Pacific Ocean. The pattern of differentiation appears to correspond to habitat types, resembling results seen in other populations of the same species. Our analyses also showed that there was no evident gene flow between the two 'sister species', the common bottlenose dolphins, and the Indo-Pacific bottlenose dolphins ( T. aduncus) occurring sympatrically in our study region. [ABSTRACT FROM AUTHOR]

Three crystal structures are presented of nematode thymidylate synthases (TS), including Caenorhabditis elegans ( Ce ) enzyme without ligands and its ternary complex with dUMP and Raltitrexed, and binary complex of Trichinella spiralis ( Ts ) enzyme with dUMP. In search of differences potentially relevant for the development of species-specific inhibitors of the nematode enzyme, a comparison was made of the present Ce and Ts enzyme structures, as well as binary complex of Ce enzyme with dUMP, with the corresponding mammalian (human, mouse and rat) enzyme crystal structures. To complement the comparison, tCONCOORD computations were performed to evaluate dynamic behaviors of mammalian and nematode TS structures. Finally, comparative molecular docking combined with molecular dynamics and free energy of binding calculations were carried out to search for ligands showing selective affinity to T. spiralis TS. Despite an overall strong similarity in structure and dynamics of nematode vs mammalian TSs, a pool of ligands demonstrating predictively a strong and selective binding to Ts TS has been delimited. These compounds, the E63 family, locate in the dimerization interface of Ts TS where they exert species-specific interactions with certain non-conserved residues, including hydrogen bonds with Thr174 and hydrophobic contacts with Phe192, Cys191 and Tyr152. The E63 family of ligands opens the possibility of future development of selective inhibitors of Ts TS and effective agents against trichinellosis. [ABSTRACT FROM AUTHOR]

Grasscutter (Thryonomys swinderianus) is a large rodent distributed across sub-Saharan Africa that is highly valued as a source of protein. There has been little effort to evaluate the genetic structure of grasscutters despite long-term harvesting pressure and over 40 years of grasscutter domestication in West Africa. Our objectives were to quantify the genetic structure of wild grasscutters, and to compare genetic variation from wild samples to those from various farmed samples within south-western Nigeria. We genotyped 145 wild and 88 domesticated individuals at 11 microsatellite loci and present results quantifying regional genetic structuring and the relative patterns of diversity among wild and domesticated grasscutter populations. Our data reflect high differentiation between wild and domesticated grasscutters, and significantly greater allelic richness and gene diversity in the former. Despite this, domesticated populations appear to have similar levels of observed heterozygosity and comparable levels of differentiation among domesticated samples relative to wild samples. This may be the result of high turnover within captive colonies, or frequent infusion of new animals. More detailed molecular and quantitative genetic studies are recommended on this species to be able to understand their natural variation, degree of connectivity and to improve strategies for domestication. [ABSTRACT FROM AUTHOR]

Type II melanoma-associated antigens (MAGE) are a subgroup of about a dozen proteins found in various locations in the genome and expressed in normal tissues, thus are not related to cancer as the type I MAGE genes. This gene family exists as a single copy in non-mammals and monotremata, but found as two copies in metatherians and occur as a diverse group in all eutherians. Our studies suggest MAGED2 as the ancestor of this subfamily and the most likely evolutionary history of eutherian type II MAGE genes is hereby proposed based on synteny conservation, phylogenetic relations, genome location, homology conservation, and the protein and gene structures. Type II genes can be divided into two: those with 13 exons (MAGED1, MAGED2, TRO, and MAGED4) and those with only one exon (MAGEE1, MAGEE2, MAGEF1, NSMCE3, MAGEH1, MAGEL2, and NDN) with different evolutionary patterns. Our results suggest a need to change the gene nomenclature to MAGE1 (the ancestral gene), currently designated as LOC103095671 and LOC100935086, in opossum and Tasmanian devil, respectively, and MAGE2 (the duplicated one), currently designated as LOC100617402 and NDNL2, respectively, to avoid confusion. We reconstructed the phylogenetic relationships among 23 mammalian species using the combined sequences of MAGED1, MAGED2, MAGEL2, and NDN, because of their high divergence, and found high levels of support, being able to resolve the phylogenetic relationships among Euarchontoglires, Laurasiatheria, Afrotheria, and Xenarthra, as an example that small, but phylogenetically informative sequences, can be very useful for resolving basal mammalian clades. [ABSTRACT FROM AUTHOR]

Arg(R)-Phe(F)-amide related peptide-1 (RFRP-1) and -3 (RFRP-3) are known as mammalian orthologs of gonadotropin-inhibitory hormone (GnIH). In mammals, these RFRPs are expressed not only in the hypothalamus and but also in gonads. Inhibitory roles of the hypothalamic and gonadal RFRP-3 in reproduction have been documented in mammals. However, functional roles of the hypothalamic and gonadal RFRP-1 in reproduction are still unclear in mammals. Therefore, in vitro studies were conducted to elucidate the direct effect of RFRP-1, a mammalian GnIH ortholog, on ovarian activities, such as steroidogenesis, apoptosis, cell proliferation and metabolism in the cyclic mouse. The ovaries collected from the proestrus mice were cultured in vitro with different doses (Control, 1 ng/ml, 10 ng/ml and 100 ng/ml) of RFRP-1 for 24 h at 37 °C. A significant dose-dependent increase in estradiol release from the ovary was detected after the treatment of RFRP-1. Therefore, changes in the ovarian activities, such as steroidogenic markers (luteinizing hormone receptors; LH-R and 3β-hydroxysteroid dehydrogenase; 3β-HSD), apoptotic markers [Poly(ADP-ribose) polymerase-1; PARP-1 and cysteine-aspartic protease; caspase-3], a cell proliferation marker (proliferating cell nuclear antigen; PCNA) and metabolic markers (GLUT-4; glucose uptake) were assessed by the treatment of RFRP-1 in the proestrus ovary. The densitometry analysis showed the treatment of RFRP-1 significantly increased the expressions of LH-R and 3β-HSD, steroidogenic markers. In contrast, the expressions of PCNA, a cell proliferation maker; PARP-1 and caspase-3, apoptotic markers were significantly decreased. Interestingly, RFRP-1 treatment further increases significantly glucose uptake and GLUT-4 receptor expression. These findings indicate that RFRP-1 possesses a stimulatory effect on ovarian steroidogenesis in the proestrus mouse. This is the first evidence showing the direct action of RFRP-1 on steroidogenesis in any vertebrate. In addition, RFRP-1 may also act directly on ovarian folliculogenesis as an inhibitory factor. [ABSTRACT FROM AUTHOR]

Copyright of Therya is the property of Asociacion Mexicana de Mastozoologia, A. C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Therya is the property of Asociacion Mexicana de Mastozoologia, A. C. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Conserved synteny denotes evolutionary preserved gene order across species. It is not well understood to which degree functional relationships between genes are preserved in syntenic blocks. Here we investigate whether protein-coding genes conserved in mammalian syntenic blocks encode gene products that serve the common functional purpose of interacting at protein level, i.e. connectivity. High connectivity among protein-protein interactions (PPIs) was only moderately associated with conserved synteny on a genome-wide scale. However, we observed a smaller subset of 3.6% of all syntenic blocks with high-confidence PPIs that had significantly higher connectivity than expected by random. Additionally, syntenic blocks with high-confidence PPIs contained significantly more chromatin loops than the remaining blocks, indicating functional preservation among these syntenic blocks. Conserved synteny is typically defined by sequence similarity. In this study, we also examined whether a functional relationship, here PPI connectivity, can identify syntenic blocks independently of orthology. While orthology-based syntenic blocks with high-confident PPIs and the connectivity-based syntenic blocks largely overlapped, the connectivity-based approach identified additional syntenic blocks that were not found by conventional sequence-based methods alone. Additionally, the connectivity-based approach enabled identification of potential orthologous genes between species. Our analyses demonstrate that subsets of syntenic blocks are associated with highly connected proteins, and that PPI connectivity can be used to detect conserved synteny even if sequence conservation drifts beyond what orthology algorithms normally can identify. [ABSTRACT FROM AUTHOR]

The metabotropic glutamate receptor 1 (mGluR1) is abundantly expressed in the mammalian central nervous system, where it regulates intracellular calcium homeostasis in response to excitatory signaling. Here, we describe heterozygous dominant mutations in GRM1 , which encodes mGluR1, that are associated with distinct disease phenotypes: gain-of-function missense mutations, linked in two different families to adult-onset cerebellar ataxia, and a de novo truncation mutation resulting in a dominant-negative effect that is associated with juvenile-onset ataxia and intellectual disability. Crucially, the gain-of-function mutations could be pharmacologically modulated in vitro using an existing FDA-approved drug, Nitazoxanide, suggesting a possible avenue for treatment, which is currently unavailable for ataxias. [ABSTRACT FROM AUTHOR]

This study investigates the genetic effect of an indigenous tradition of deliberate and controlled interbreeding between wild and domestic Rangifer. The results are interpreted in the context of conservation concerns and debates on the origin of domestic animals. The study is located in Northeastern Zabaĭkal'e, Russia at approximately 57 degrees North latitude. Blood and skin samples, collected from wild and domestic Rangifer, are analyzed for their mt DNA and microsatellite signatures. Local husbandry traditions are documented ethnographically. The genetic data are analyzed with special reference to indigenous understandings of the distinctions between local domestic types and wild Rangifer. The genetic results demonstrate a strong differentiation between wild and domestic populations. Notably low levels of mt DNA haplotype sharing between wild and domestic reindeer, suggest mainly male-mediated gene flow between the two gene pools. The nuclear microsatellite results also point to distinct differences between regional domestic clusters. Our results indicate that the Evenki herders have an effective breeding technique which, while mixing pedigrees in the short term, guards against wholesale introgression between wild and domestic populations over the long term. They support a model of domestication where wild males and domestic females are selectively interbred, without hybridizing the two populations. Our conclusions inform a debate on the origins of domestication by documenting a situation where both wild and domestic types are in constant interaction. The study further informs a debate in conservation biology by demonstrating that certain types of controlled introgression between wild and domestic types need not reduce genetic diversity. [ABSTRACT FROM AUTHOR]

Information concerning population structure and genetic diversity in Stenella clymene is still scarce. Previous studies raised questions regarding the species' position in the genus Stenella and suggested that S. clymene might be of hybrid origin. The present study analyzed the mitochondrial control region (D-loop), cytochrome oxidase I (CoI), and cytochrome b (Cyt b) of northeastern Brazil individuals and compared them with S. clymene sequences from the North Atlantic Ocean and Gulf of Mexico. Brazilian individuals showed high haplotype diversity (D-loop: 1.00/p = 0.02; CoI: 0.99/p = 0.04; Cyt b: 0.96/p = 0.06) and probably constitute one population (South Atlantic Ocean). Significant differentiation and high FST values (D-loop: FST = 0.88/p = 0.00; CoI: FST = 0.70/p = 0.00; Cyt b: FST = 0.96/p = 0.00) were found between population units from the North and South Atlantic Ocean. For Cyt b, population units from the South Atlantic Ocean and Gulf of Mexico showed significant differentiation, but the FST value was low (FST = 0.11/p = 0.0). In addition, the haplotype network suggests connectivity between South Atlantic Ocean and Gulf of Mexico units. More effort focusing on S. clymene is needed to better elucidate the patterns of population structure within this species and, thus, provide sufficient data for conservation strategies. [ABSTRACT FROM AUTHOR]

The factors guiding retrotransposon insertion site preference are not well understood. Different types of retrotransposons share common replication machinery and yet occupy distinct genomic domains. Autonomous long interspersed elements accumulate in gene-poor domains and their nonautonomous short interspersed elements accumulate in gene-rich domains. To determine genomic factors that contribute to this discrepancy we analyzed the distribution of retrotransposons within the framework of chromosomal domains and regulatory elements. Using comparative genomics, we identified large-scale conserved patterns of retrotransposon accumulation across several mammalian genomes. Importantly, retrotransposons that were active after our sample-species diverged accumulated in orthologous regions. This suggested a similar evolutionary interaction between retrotransposon activity and conserved genome architecture across our species. In addition, we found that retrotransposons accumulated at regulatory element boundaries in open chromatin, where accumulation of particular retrotransposon types depended on insertion size and local regulatory element density. From our results, we propose a model where density and distribution of genes and regulatory elements canalize retrotransposon accumulation. Through conservation of synteny, gene regulation and nuclear organization, mammalian genomes with dissimilar retrotransposons follow similar evolutionary trajectories. [ABSTRACT FROM AUTHOR]

In many species, spermatogenesis involves more cell divisions than oogenesis, and the male germline, therefore, accumulates more DNA replication errors, a phenomenon known as male mutation bias. The extent of male mutation bias (α) is estimated by comparing substitution rates of the X, Y, and autosomal chromosomes, as these chromosomes spend different proportions of their time in the germlines of the two sexes. Malemutation bias has been characterized in placental and marsupial mammals as well as birds, but analyses in monotremes failed to detect any such bias. Monotremes are an ancient lineage of egg-laying mammals with distinct biological properties, which include unique germline features. Here, we sought to assess the presence and potential characteristics of male mutation bias in platypus and the short-beaked echidna based on substitution rate analyses of X, Y, and autosomes. We established the presence of moderate male mutation bias in monotremes, corresponding to an α value of 2.12-3.69. Given that it has been unclear what proportion of the variation in substitution rates on the different chromosomal classes is really due to differential number of replications, we analyzed the influence of other confounding forces (selection, replication-timing, etc.) and found that male mutation bias is the main force explaining the between-chromosome classes differences in substitution rates. Finally, we estimated the proportion of variation at the gene level in substitution rates that is owing to replication effects and found that this phenomenon can explain>68%of these variations in monotremes, and in control species, rodents, and primates. [ABSTRACT FROM AUTHOR]

Invasive carnivores often cause heavy damage to native species on small islands. Endangered Amami rabbit ( Pentalagus furnessi) populations have been fragmented into a north-isolated population (NI) and a south-large population (SL) caused by predation pressure from the invasive small Indian mongoose ( Herpestes auropunctatus) on Amami Oshima Island in southern Japan. We investigated the genetic structure of these rabbit populations to determine the effects of fragmentation. We collected rabbit feces from most of the Amami Oshima Island habitat and sequenced the mitochondrial DNA (mtDNA) control region along with its 5′-flanking region (312 bp) and genotyped eight microsatellite DNA loci. Genetic diversity was lower in the NI than that in the SL population, and F values between the two populations were significantly higher than zero in both the mtDNA and microsatellite DNA. Bayesian clustering analyses suggested four ancestral clusters of Amami rabbit, but clear genetic structure was not observed. A partial Mantel test supported isolation-by-distance but not habitat fragmentation. These results suggest that the low genetic diversity in the NI population was caused by the small population size after fragmentation; however, the difference in genetic structure between the two populations was caused by isolation-by-distance and the structure has been maintained. [ABSTRACT FROM AUTHOR]

Throughout their entire life cycle, mRNAs are associated with RNA-binding proteins (RBPs), forming ribonucleoprotein (RNP) complexes with highly dynamic compositions. Their interplay is one key to control gene regulatory mechanisms from mRNA synthesis to decay. To assay the global scope of RNA-protein interactions, we and others have published a method combining crosslinking with highly stringent oligo(dT) affinity purification to enrich proteins associated with polyadenylated RNA (poly(A)+ RNA). Identification of the poly(A)+ RNA-bound proteome (also: mRNA interactome capture) has by now been applied to a diversity of cell lines and model organisms, uncovering comprehensive repertoires of RBPs and hundreds of novel RBP candidates. In addition to determining the RBP catalog in a given biological system, mRNA interactome capture allows the examination of changes in protein-mRNA interactions in response to internal and external stimuli, altered cellular programs and disease. [ABSTRACT FROM AUTHOR]

The nuclear export of mRNAs is an important yet little understood part of eukaryotic gene expression. One of the easiest methods for monitoring mRNA export in mammalian tissue culture cells is through the microinjection of DNA plasmids into the nucleus and monitoring the distribution of the transcribed product over time. Here we describe how to setup a microscope equipped with a micromanipulator used in cell microinjections, and we explain how to perform a nuclear mRNA export assay and obtain the nuclear export rate for any given mRNA. [ABSTRACT FROM AUTHOR]

The primary host of plague in the Qinghai-Tibet Plateau (QTP), China, is Marmota himalayana, which plays an essential role in the maintenance, transmission, and prevalence of plague. To achieve a more clear insight into the differentiation of M. himalayana, complete cytochrome b (cyt b) gene and 11 microsatellite loci were analyzed for a total of 423 individuals from 43 localities in the northeast of the QTP. Phylogenetic analyses with maximum likelihood and Bayesian inference methods showed that all derived haplotypes diverged into two primary well-supported monophyletic lineages, I and II, which corresponded to the referential sequences of two recognized subspecies, M. h. himalayana and M. h. robusta, respectively. The divergence between the two lineages was estimated to be at about 1.03 million years ago, nearly synchronously with the divergence between M. baibacina and M. kastschenkoi and much earlier than that between M. vancouverensis and M. caligata. Genetic structure analyses based on the microsatellite dataset detected significant admixture between the two lineages in the mixed region, which verified the intraspecies level of the differentiation between the two lineages. Our results for the first time demonstrated the coexistence of M. h. himalayana and M. h. robusta, and also, determined the distribution range of the two subspecies in the northeast of QTP. We provided fundamental information for more effective plague control in the QTP. [ABSTRACT FROM AUTHOR]

Capture of retroviral envelope genes is likely to have played a role in the emergence of placental mammals, with evidence for multiple, reiterated, and independent capture events occurring in mammals, and be responsible for the diversity of present day placental structures. Here, we uncover a full-length endogenous retrovirus envelope protein, dubbed HEMO [human endogenous MER34 (mediumreiteration- frequency-family-34) ORF], with unprecedented characteristics, because it is actively shed in the blood circulation in humans via specific cleavage of the precursor envelope protein upstream of the transmembrane domain. At variance with previously identified retroviral envelope genes, its encoding gene is found to be transcribed from a unique CpG-rich promoter not related to a retroviral LTR, with sites of expression including the placenta as well as other tissues and rather unexpectedly, stem cells as well as reprogrammed induced pluripotent stem cells (iPSCs), where the protein can also be detected. We provide evidence that the associated retroviral capture event most probably occurred >100 Mya before the split of Laurasiatheria and Euarchontoglires, with the identified retroviral envelope gene encoding a full-length protein in all simians under purifying selection and with similar shedding capacity. Finally, a comprehensive screen of the expression of the gene discloses high transcript levels in several tumor tissues, such as germ cell, breast, and ovarian tumors, with in the latter case, evidence for a histotype dependence and specific protein expression in clear-cell carcinoma. Altogether, the identified protein could constitute a "stemness marker" of the normal cell and a possible target for immunotherapeutic approaches in tumors. [ABSTRACT FROM AUTHOR]

The interordinal relationships of Laurasiatherian mammals are currently one of the most controversial questions in mammalian phylogenetics. Previous studies mainly relied on coding sequences (CDS) and seldom used noncoding sequences. Here, by data mining public genome data, we compiled an intron data set of 3,638 genes (all introns from a protein-coding gene are considered as a gene) (19,055,073 bp) and a CDS data set of 10,259 genes (20,994,285 bp), covering all major lineages of Laurasiatheria (except Pholidota). We found that the intron data contained stronger and more congruent phylogenetic signals than the CDS data. In agreement with this observation, concatenation and species-tree analyses of the intron data set yielded well-resolved and identical phylogenies, whereas the CDS data set produced weakly supported and incongruent results. Further analyses showed that the phylogeny inferred from the intron data is highly robust to data subsampling and change in outgroup, but the CDS data produced unstable results under the same conditions. Interestingly, gene tree statistical results showed that the most frequently observed gene tree topologies for the CDS and intron data are identical, suggesting that the major phylogenetic signal within the CDS data is actually congruent with that within the intron data. Our final result of Laurasiatheria phylogeny is (Eulipotyphla,((Chiroptera, Perissodactyla), (Carnivora, Cetartiodactyla))), favoring a close relationship between Chiroptera and Perissodactyla. Our study 1) provides a well-supported phylogenetic framework for Laurasiatheria, representing a step towards ending the long-standing "hard" polytomy and 2) argues that intron within genome data is a promising data resource for resolving rapid radiation events across the tree of life. [ABSTRACT FROM AUTHOR]

The Malagasy carnivorans (Eupleridae) comprise seven genera and up to ten species, depending on the authority, and, within the past decades, two new taxa have been described. The family is divided into two subfamilies, the Galidiinae, mongoose-like animals, and the Euplerinae, with diverse body forms. To verify the taxonomic status of Galidiinae species, including recently described taxa, as well as some recognized subspecies, we studied intrageneric genetic variation and structure, using both mitochondrial and nuclear markers. Our results suggest the recognition of four species in the Galidiinae, rendering each genus monospecific. We propose to recognize three subspecies in Galidia elegans ( G. e. dambrensis, G. e. elegans, and G. e. occidentalis), two subspecies in Mungotictis decemlineata ( M. d. decemlineata and M. d. lineata), and two subspecies in Galidictis fasciata ( G. f. fasciata and G. f. grandidieri, the latter was recently described as a distinct species). Our results indicate also that Salanoia durrelli should be treated as a junior synonym of Salanoia concolor. Low levels of intraspecific divergence revealed some geographical structure for the Galidiinae taxa, suggesting that environmental barriers have isolated certain populations in recent geological time. All taxa, whether at the species or subspecies level, need urgent conservation attention, particularly those with limited geographical distributions, as all are threatened by forest habitat degradation. [ABSTRACT FROM AUTHOR]

Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are now the mainstay of research on hypertension, obesity and neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J Hered 52(6):275-278, 1961). Despite this wealth of genetic and phenotypic diversity, the ability to manipulate and interrogate the genetic basis of existing phenotypes in rat strains and the methodology to generate new rat models has lagged significantly behind the advances made with its close cousin, the laboratory mouse. However, recent technical developments in stem cell biology and genetic engineering have again brought the rat to the forefront of biomedical studies and enabled researchers to exploit the increasingly accessible wealth of genome sequence information. In this review, we will describe how a breakthrough in understanding the molecular basis of self-renewal of the pluripotent founder cells of the mammalian embryo, embryonic stem (ES) cells, enabled the derivation of rat ES cells and their application in transgenesis. We will also describe the remarkable progress that has been made in the development of gene editing enzymes that enable the generation of transgenic rats directly through targeted genetic modifications in the genomes of zygotes. The simplicity, efficiency and cost-effectiveness of the CRISPR/Cas gene editing system, in particular, mean that the ability to engineer the rat genome is no longer a limiting factor. The selection of suitable targets and gene modifications will now become a priority: a challenge where ES culture and gene editing technologies can play complementary roles in generating accurate bespoke rat models for studying biological processes and modelling human disease. [ABSTRACT FROM AUTHOR]

Genome editing is facilitating the manipulation of genomes on an unprecedented scale. It promises to revolutionize our ability to study gene function and generate models of human genetic disease in a range of organisms, most notably in mammals such as the mouse. Is this new technology likely to be disruptive to our research practices in any way? Will it alter the ways in which we implement the ethical imperatives of the 3Rs? In short, what ethical questions are raised by genome editing of mammals in a biomedical research context? [ABSTRACT FROM AUTHOR]

The 70 kilodalton heat shock proteins (Hsp70) are highly conserved molecular chaperones which have a crucial role in the stress response of the cell. In mammals, the Hsp70 proteins are encoded by a cluster of three genes: HSPA1A, HSPA1B and HSPA1L. In bovines, this cluster is located on chromosome 23 downstream of the major histocompatibility complex (Bo LA). We detected inconsistencies in the location of markers on the Hsp70 genes reported in the literature that pointed to a potential deletion in the bovine reference genome UMD 3.1.1. An in silico analysis of the bovine genomic region of the Hsp70 cluster, using available information from public databases, confirmed the existence of a deletion of 11.1-kb spanning the HSPA1B gene and the intergenic region between HSPA1B and HSPA1A. Although we originally considered this an assembly error, it is most likely a particular condition of L1 Dominette 01449, the cow sequenced in the Bovine Genome Project. Moreover, we suggest a new classification of bovine Hsp70 sequences reported in NCBI and a reassignment of the location of SNPs from db SNP that map to the deletion on BTA23. We also compared the location of selected transcription factor binding sites on the promoters of HSPA1A and HSPA1B. The results generated in the present work could be helpful to refine the reference genome of an important livestock species and also to understand the role and the regulation of the bovine Hsp70 genes. [ABSTRACT FROM AUTHOR]

Platelet Derived Growth Factor receptors (PDGFRs), members of receptor tyrosine kinase superfamily, play essential roles in early hematopoiesis, angiogenesis and organ development. Dysregulation of PDGF receptor signaling under pathological conditions associates with cancers, vascular diseases, and fibrotic diseases. Therefore, they are attractive targets in drug development. Like any other membrane proteins with a single-pass transmembrane domain, the high-resolution structural information of the full-length PDGF receptors is still not resolved. It is caused, at least in part, by the technical challenges in the expression and purification of the functional, full-length PDGF receptors. Herein, we reported our experimental details in expression and purification of the full-length PDGFRβ from mammalian cells. We found that purified PDGFRβ remained in two different oligomeric states, presumably the monomer and the dimer, with basal kinase activity in detergent micelles. Addition of PDGF-B promoted dimerization and elevated kinase activity of the receptor, suggesting that purified receptors were functional. [ABSTRACT FROM AUTHOR]

Assisted reproductive technologies in all mammals are critically dependent on the quality of the oocytes used to produce embryos. For reasons not fully clear, oocytes matured in vitro tend to be much less competent to become fertilized, advance to the blastocyst stage, and give rise to live young than their in vivo-produced counterparts, particularly if they are derived from immature females. Here we show that a chemically defined maturation medium supplemented with three cytokines (FGF2, LIF, and IGF1) in combination, so-called "FLI medium," improves nuclear maturation of oocytes in cumulus-oocyte complexes derived from immature pig ovaries and provides a twofold increase in the efficiency of blastocyst production after in vitro fertilization. Transfer of such blastocysts to recipient females doubles mean litter size to about nine piglets per litter. Maturation of oocytes in FLI medium, therefore, effectively provides a fourfold increase in piglets born per oocyte collected. As they progress in culture, the FLI-matured cumulus-oocyte complexes display distinctly different kinetics of MAPK activation in the cumulus cells, much increased cumulus cell expansion, and an accelerated severance of cytoplasmic projections between the cumulus cells outside the zona pellucida and the oocyte within. These events likely underpin the improvement in oocyte quality achieved by using the FLI medium. [ABSTRACT FROM AUTHOR]

Traditional subspecies call attention to differences between geographic populations with research potential, but their value is often in need of revision. Genetic data can be useful for evaluating the taxonomic validity of historical species and subspecies designations or for identifying morphologically cryptic divergent lineages worthy of further in-depth taxonomic study. The desert hedgehog ( Paraechinus aethiopicus ) has a wide but fragmented distribution in arid and semi-arid habitats from the northwest to the northeast of Africa and southwestern Asia, and its taxonomy is still unclear. We used mitochondrial (cytochrome b , Cyt b , and 12S ribosomal RNA, 12S ) and nuclear (breast cancer type 1 susceptibility protein, BRCA1 , and apolipoprotein B, Apob ) DNA sequence data to assess the degree of genetic divergence between two of its three major proposed subspecies: Arabian ( P. a. dorsalis ) and Northwest African ( P. a. deserti ); this is the first molecular evaluation of the taxonomy of P. aethiopicus . Phylogenetic analyses, comparison of interspecific and intraspecific genetic distances observed across hedgehog species, and molecular species delimitation methods (distance-based clustering and tree-based), all indicate a level of genetic differentiation between dorsalis and deserti that is compatible with their taxonomic separation. Their divergence in the studied genes were consistently comparable to, or greater than, several intrageneric and a few intergeneric distances in hedgehogs. The Cyt b net Kimura 2-parameter distance between dorsalis and deserti was 10.8 ± 1.3%, which is about the mean between congeneric species in reviews of Cyt b distances for mammals. This study, as a test of the genetic distinctiveness of dorsalis and deserti , suggests that they represent evolutionarily significant units and flags them for future phylogeographic and taxonomic investigations. [ABSTRACT FROM AUTHOR]

Manatees are a vulnerable, charismatic sentinel species from the evolutionarily divergent Afrotheria. Manatee health and resistance to infectious disease is of great concern to conservation groups, but little is known about their immune system. To develop manatee-specific tools for monitoring health, we first must have a general knowledge of how the immunoglobulin heavy (IgH) chain locus is organized and transcriptionally expressed. Using the genomic scaffolds of the Florida manatee ( Trichechus manatus latirostris ), we characterized the potential IgH segmental diversity and constant region isotypic diversity and performed the first Afrotherian repertoire analysis. The Florida manatee has low V(D)J combinatorial diversity (3744 potential combinations) and few constant region isotypes. They also lack clan III V segments, which may have caused reduced VH segment numbers. However, we found productive somatic hypermutation concentrated in the complementarity determining regions. In conclusion, manatees have limited IGHV clan and combinatorial diversity. This suggests that clan III V segments are essential for maintaining IgH locus diversity. [ABSTRACT FROM AUTHOR]

The Mohave ground squirrel ( Xerospermophilus mohavensis) is endemic to the western Mojave Desert of California and is state-listed as Threatened. This species is of conservation concern because of the potential for large-scale renewable energy development within its range. Recent evidence suggests that this threatened species may at least occasionally hybridize with the closely related round-tailed ground squirrel ( Xerospermophilus tereticaudus) where the species come into contact. As a result, there is great interest in the distribution of the Mohave ground squirrel, especially where it may come in contact with the round-tailed ground squirrel. One of the least understood portions of the Mohave ground squirrel distribution is around the Hinkley Valley, west of the city of Barstow, where its eastern range limits come into proximity with the round-tailed ground squirrel. To document what is known of the fine-scale distribution of these congeners in this region, we assemble and review all available trapping survey data from this area and combine the field survey data with genetic analyses of recently collected samples. Our evaluation of trapping records confirms that there are no reliable recent reports of Mohave ground squirrels in the Hinkley Valley itself, which has been developed for agriculture. The species appears to be largely restricted to the relatively undisturbed desert habitat west of Hinkley. In contrast, a number of round-tailed ground squirrel records exist for the Hinkley Valley, some dating back to 1977. Using 13 nuclear microsatellite loci from 55 ground squirrel samples collected across this region, we confirm the presence of genetically pure Mohave and round-tailed ground squirrels. However, 3 individuals collected in the Hinkley Valley that were identified as round-tailed ground squirrels on the basis of external characteristics show evidence of Mohave ground squirrel ancestry. In similar fashion, 3 animals from the desert region west of Hinkley were found to have some round-tailed ground squirrel genetic ancestry in spite of external features typical of Mohave ground squirrels. While round-tailed ground squirrels seem to be the dominant species in Hinkley Valley and Mohave ground squirrels seem dominant in the desert environment to the west, hybridization does appear to occur occasionally. Further, when these species hybridize, at least some hybrids are fertile, and backcrossing appears to occur in both parental directions. It is important to investigate this phenomenon more closely to evaluate possible threats to the genetic integrity of the Mohave ground squirrel. [ABSTRACT FROM AUTHOR]

Joint quantification of genetic and epigenetic effects on gene expression is important for understanding the establishment of complex gene regulation systems in living organisms. In particular, genomic imprinting and maternal effects play important roles in the developmental process of mammals and flowering plants. However, the influence of these effects on gene expression are difficult to quantify because they act simultaneously with c/s-regulatory mutations. Here we propose a simple method to decompose c/s-regulatory (i.e., allelic genotype), genomic imprinting [i.e., parent-of-origin (PO)], and maternal [i.e., maternal genotype (MG)] effects on allele-specific gene expression using RNA-seq data obtained from reciprocal crosses. We evaluated the efficiency of method using a simulated dataset and applied the method to whole-body Drosophila and mouse trophoblast stem cell (TSC) and liver RNA-seq data. Consistent with previous studies, we found little evidence of PO and MG effects in adult Drosophila samples. In contrast, we identified dozens and hundreds of mouse genes with significant PO and MG effects, respectively. Interestingly, a similar number of genes with significant PO effect were detect in mouse TSCs and livers, whereas more genes with significant MG effect were observed in livers. Further application of this method will clarify how these three effects influence gene expression levels in different tissues and developmental stages, and provide novel insight into the evolution of gene expression regulation. [ABSTRACT FROM AUTHOR]

Finlayson’s squirrel ( Callosciurus finlaysonii ) is distributed in lowland forests in Southeast Asia. The pelage colour is conspicuously polymorphic, and 16 subspecies have been described based on pelage colour patterns. Among them, 12 subspecies are distributed in Thailand, of which 7 are on the mainland and 5 are on islands. In addition, the distribution range of another closely related species, Pallas’s squirrel ( Callosciurus erythraeus ), overlaps the range of C. finlaysonii in western Thailand. In this study, phylogenetic analysis based on mitochondrial DNA suggested that C. finlaysonii and C. erythraeus did not form separate monophyletic groups. This C. finlaysonii / C. erythraeus complex in Thailand consisted of seven divergent groups, some of which may have arisen from isolation due to large rivers and seas: (1) C. f. nox / cinnamomeus , (2) C. f. finlaysonii / folletti / trotteri , (3) C. f. menamicus , (4) C. erythraeus , (5) C. f. annellatus , (6) C. f. bocourti / boonsongi / floweri , and (7) C. f. frandseni / albivexilli . Pelage colour did not consistently correspond to these genetic groups, suggesting that specific colours may have been acquired multiple times or the genes associated with colour may have variations and polymorphisms within subspecies. Several small populations in the lowlands and on small islands had lower genetic diversity. To conserve the local genetic diversity of C. finlaysonii , it may be necessary to enact legal restrictions on their trade and hunting. [ABSTRACT FROM AUTHOR]

Social groups of bats that operate under fission-fusion dynamics tend to establish and maintain non-random associations. We examined the social and genetic structure of the Leisler's bat (Nyctalus leisleri), a species that is typical of tree-dwelling and long-distance migratory species in Europe. We used long-term co-occurrence data (capture-recapture sampling of roosting individuals) in combination with individual genetic relatedness (inferred from a set of microsatellite markers) to assess relationships between structural, temporal and genetic properties of roosting groups. Our results showed that social structure in groups of roosting Leisler's bat was not random. Social clusters revealed by network analysis were almost identical to demographic cohorts, which indicates that Leisler's bats are able to maintain social bonds only over a single season. After the period of active maternal care, roosting groups became smaller with a significantly higher level of genetic relatedness among adult females in contrast to the pregnancy and lactation stages. This provides some evidence that temporal social associations may be positively correlated with genetic relatedness. Low recapture rates of bats across seasons in light of natal philopatry indicates a shorter life span of individuals likely due to high mortality during long distance migratory movements. This probably has the most significant effect on the social system of this species. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) was first described as a cytokine 50 years ago, and emerged in mammals as a pleiotropic protein with pro-inflammatory, chemotactic, and growth-promoting activities. In addition, MIF has gained substantial attention as a pivotal upstream mediator of innate and adaptive immune responses and with pathologic roles in several diseases. Of less importance in mammals is an intrinsic but non-physiologic enzymatic activity that points to MIF's evolution from an ancient defense molecule. Therefore, it is not surprising that mif -like genes also have been found across a range of different organisms including bacteria, plants, protozoa, helminths, molluscs, arthropods, fish, amphibians and birds. While Genebank analysis identifying mif -like genes across species is extensive, contained herein is an overview of the non-mammalian MIF-like proteins that have been most well studied experimentally. For many of these organisms, MIF contributes to an innate defense system or plays a role in development. For parasitic organisms however, MIF appears to function as a virulence factor aiding in the establishment or persistence of infection by modulating the host immune response. Consequently, a combined targeting of both parasitic and host MIF could lead to more effective treatment strategies for parasitic diseases of socioeconomic importance. [ABSTRACT FROM AUTHOR]

Several variants in the KIT, PAX3 and MITF genes have previously been associated with white markings in horses. In this study, we examined eight variants of these genes in 70 Menorca Purebred horses (PRMe, only black solid-coloured horses) and 70 Spanish Purebred horses (PRE, different coat colour patterns) that were scored for the extent of white markings. A maximum-likelihood chi-square test, logistic regression model and ridge regression analyses showed that a missense mutation (p.Arg682His) in KIT was associated with white facial markings ( P < 0.05) and with total white markings ( P < 0.05) in PRMe horses. The relative contribution of this variant to white markings in PRMe horses was estimated at 47.6% (head) and 43.4% (total score). In PRE horses, this variant was also associated with hindlimb scores ( P < 0.05) with a relative contribution of 41.2%. The g.20147039C>T intronic variant located 29.9 kb downstream from the transcription start site of the MITF gene was associated with less white markings on forelimbs ( P < 0.05) in PRMe horses, with a relative contribution of 63.9%, whereas in PRE horses this variant was associated with white facial markings ( P < 0.05), with a relative contribution of 63.9%. No significant associations were found for PAX3 variants in these breeds. These results show that KIT and MITF variants are involved in the white marking patterns of both PRMe and PRE horses, providing breeders with an opportunity to use genetic testing to aid in breeding for their desired level of white markings. [ABSTRACT FROM AUTHOR]

Obtaining the representative morphological data required for traditional taxonomy is difficult, and sometimes impossible, for cetaceans, especially large ones. As a result, three quarters of the 88 currently recognized extant species have no subspecies and 40 taxa likely have additional unnamed taxa. Conservation needs give urgency to improving taxonomy because unnamed taxa are unlikely to receive protection equivalent to that received by named taxa. Genetic data can improve efforts to delimit subspecies, but the markers and methods used have varied and the magnitude of genetic difference used to justify subspecies distinctions across studies has also varied. Here, we define the concepts of populations, subspecies, and species to establish a foundation for developing guidelines (data to include and analyses to conduct) and quantitative standards (the magnitude of differentiation expected at different taxonomic levels) for using genetic data to support taxonomic recognition. Our definition is particularly applicable to data-poor groups because it allows for naming a subspecies when there is uncertainty about whether lineages have diverged sufficiently for species-level recognition. This allows a species that lacks convincing data for lineage divergence to be recognized as a subspecies while sufficient data are accrued, which could take decades for some cetaceans. [ABSTRACT FROM AUTHOR]

Background: Many genetic diseases are caused by mutations in non-coding regions of the genome. These mutations are frequently found in enhancer sequences, causing disruption to the regulatory program of the cell. Enhancers are short regulatory sequences in the non-coding part of the genome that are essential for the proper regulation of transcription. While the experimental methods for identification of such sequences are improving every year, our understanding of the rules behind the enhancer activity has not progressed much in the last decade. This is especially true in case of tissue-specific enhancers, where there are clear problems in predicting specificity of enhancer activity. Results: We show a random-forest based machine learning approach capable of matching the performance of the current state-of-the-art methods for enhancer prediction. Then we show that it is, similarly to other published methods, frequently cross-predicting enhancers as active in different tissues, making it less useful for predicting tissue specific activity. Then we proceed to show that the problem is related to the fact that the enhancer predicting models exhibit a bias towards predicting gene promoters as active enhancers. Then we show that using a two-step classifier can lead to lower cross-prediction between tissues. Conclusions: We provide whole-genome predictions of human heart and brain enhancers obtained with two-step classifier. [ABSTRACT FROM AUTHOR]

Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1-2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging 'dynamic complex' rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and frequently break and reform throughout the cell cycle. [ABSTRACT FROM AUTHOR]