Premutation in the Fragile X Mental Retardation 1 (FMR1) Gene Affects Maternal Zn-milk and Perinatal Brain Bioenergetics and Scaffolding.

Fragile X premutation alleles have 55-200 CGG repeats in the 5' UTR of the FMR1 gene. Altered zinc (Zn) homeostasis has been reported in fibroblasts from >60 years old premutation carriers, in which Zn supplementation significantly restored Zn-dependent mitochondrial protein import/processing and function. Given that mitochondria play a critical role in synaptic transmission, brain function, and cognition, we tested FMRP protein expression, brain bioenergetics, and expression of the Zn-dependent synaptic scaffolding protein SH3 and multiple ankyrin repeat domains 3 (Shank3) in a knock-in (KI) premutation mouse model with 180 CGG repeats. Mitochondrial outcomes correlated with FMRP protein expression (but not FMR1 gene expression) in KI mice and human fibroblasts from carriers of the pre- and full-mutation. Significant deficits in brain bioenergetics, Zn levels, and Shank3 protein expression were observed in the Zn-rich regions KI hippocampus and cerebellum at PND21, with some of these effects lasting into adulthood (PND210). A strong genotype × age interaction was observed for most of the outcomes tested in hippocampus and cerebellum, whereas in cortex, age played a major role. Given that the most significant effects were observed at the end of the lactation period, we hypothesized that KI milk might have a role at compounding the deleterious effects on the FMR1 genetic background. A higher gene expression of ZnT4 and ZnT6, Zn transporters abundant in brain and lactating mammary glands, was observed in the latter tissue of KI dams. A cross-fostering experiment allowed improving cortex bioenergetics in KI pups nursing on WT milk. Conversely, WT pups nursing on KI milk showed deficits in hippocampus and cerebellum bioenergetics. A highly significant milk type × genotype interaction was observed for all three-brain regions, being cortex the most influenced. Finally, lower milk-Zn levels were recorded in milk from lactating women carrying the premutation as well as other Zn-related outcomes (Zn-dependent alkaline phosphatase activity and lactose biosynthesis-whose limiting step is the Zn-dependent β-1,4-galactosyltransferase). In premutation carriers, altered Zn homeostasis, brain bioenergetics and Shank3 levels could be compounded by Zn-deficient milk, increasing the risk of developing emotional and neurological/cognitive problems and/or FXTAS later in life

Phylogeny and evolutionary history of glycogen synthase kinase 3/SHAGGY-like kinase genes in land plants

Background: GSK3 (glycogen synthase kinase 3) genes encode signal transduction proteins with roles in a variety of biological processes in eukaryotes. In contrast to the low copy numbers observed in animals, GSK3 genes have expanded into a multi-gene family in land plants (embryophytes), and have also evolved functions in diverse plant specific processes, including floral development in angiosperms. However, despite previous efforts, the phylogeny of land plant GSK3 genes is currently unclear. Here, we analyze genes from a representative sample of phylogenetically pivotal taxa, including basal angiosperms, gymnosperms, and monilophytes, to reconstruct the evolutionary history and functional diversification of the GSK3 gene family in land plants. Results: Maximum Likelihood phylogenetic analyses resolve a gene tree with four major gene duplication events that coincide with the emergence of novel land plant clades. The single GSK3 gene inherited from the ancestor of land plants was first duplicated along the ancestral branch to extant vascular plants, and three subsequent duplications produced three GSK3 loci in the ancestor of euphyllophytes, four in the ancestor of seed plants, and at least five in the ancestor of angiosperms. A single gene in the Amborella trichopoda genome may be the sole survivor of a sixth GSK3 locus that originated in the ancestor of extant angiosperms. Homologs of two Arabidopsis GSK3 genes with genetically confirmed roles in floral development, AtSK11 and AtSK12, exhibit floral preferential expression in several basal angiosperms, suggesting evolutionary conservation of their floral functions. Members of other gene lineages appear to have independently evolved roles in plant reproductive tissues in individual taxa. Conclusions: Our phylogenetic analyses provide the most detailed reconstruction of GSK3 gene evolution in land plants to date and offer new insights into the origins, relationships, and functions of family members. Notably, the diversity of this “green” branch of the gene family has increased in concert with the increasing morphological and physiological complexity of land plant life forms. Expression data for seed plants indicate that the functions of GSK3 genes have also diversified during evolutionary time

A cross-species alignment tool (CAT)

<p>Abstract</p> <p>Background</p> <p>The main two sorts of automatic gene annotation frameworks are <it>ab initio </it>and alignment-based, the latter splitting into two sub-groups. The first group is used for intra-species alignments, among which are successful ones with high specificity and speed. The other group contains more sensitive methods which are usually applied in aligning inter-species sequences.</p> <p>Results</p> <p>Here we present a new algorithm called <it>CAT </it>(for Cross-species Alignment Tool). It is designed to align mRNA sequences to mammalian-sized genomes. <it>CAT </it>is implemented using C scripts and is freely available on the web at <url>http://xat.sourceforge.net/</url>.</p> <p>Conclusions</p> <p>Examined from different angles, <it>CAT </it>outperforms other extant alignment tools. Tested against all available mouse-human and zebrafish-human orthologs, we demonstrate that <it>CAT </it>combines the specificity and speed of the best intra-species algorithms, like <it>BLAT </it>and <it>sim4</it>, with the sensitivity of the best inter-species tools, like <it>GeneWise</it>.</p

Evolutionary Analysis of the LAFL Genes Involved in the Land Plant Seed Maturation Program

Seeds are one of the most significant innovations in the land plant lineage, critical to the diversification and adaptation of plants to terrestrial environments. From perspective of seed evo-devo, the most crucial developmental stage in this innovation is seed maturation, which includes accumulation of storage reserves, acquisition of desiccation tolerance, and induction of dormancy. Based on previous studies of seed development in the model plant Arabidopsis thaliana, seed maturation is mainly controlled by the LAFL regulatory network, which includes LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) of the NF-YB gene family, and ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2 (LEAFY COTYLEDON2) of the B3-AFL gene family. In the present study, molecular evolution of these LAFL genes was analyzed, using representative species from across the major plant lineages. Additionally, to elucidate the molecular mechanisms of the seed maturation program, co-expression pattern analyses of LAFL genes were conducted across vascular plants. The results show that the origin of AFL gene family dates back to a common ancestor of bryophytes and vascular plants, while LEC1-type genes are only found in vascular plants. LAFL genes of vascular plants likely specify their co-expression in two different developmental phrases, spore and seed maturation, respectively, and expression patterns vary slightly across the major vascular plants lineages. All the information presented in this study will provide insights into the origin and diversification of seed plants.National Natural Science Foundation of China (NSFC) [91231105]SCI(E)ARTICLE

Gene conversion in the rice genome

Background: Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion. Results: To characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program. Over 60% of the conversions we detected were between chromosomes. We found that the inter-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P < 0.05). The frequencies of gene conversion on the same chromosome decreased with the physical distance between gene conversion partners. Ka/Ks analysis indicates that gene conversion is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less than ten percent. Pseudogenes in the rice genome with low similarity to Arabidopsis genes showed greater likelihood for gene conversion than those with high similarity to Arabidopsis genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were involved in conversion events. Conclusion: The evolution of gene families in the rice genome may have been accelerated by conversion with pseudogenes. Our analysis suggests a possible role for gene conversion in the evolution of pathogen-response genes

Gene conversion in the rice genome

<p>Abstract</p> <p>Background</p> <p>Gene conversion causes a non-reciprocal transfer of genetic information between similar sequences. Gene conversion can both homogenize genes and recruit point mutations thereby shaping the evolution of multigene families. In the rice genome, the large number of duplicated genes increases opportunities for gene conversion.</p> <p>Results</p> <p>To characterize gene conversion in rice, we have defined 626 multigene families in which 377 gene conversions were detected using the GENECONV program. Over 60% of the conversions we detected were between chromosomes. We found that the inter-chromosomal conversions distributed between chromosome 1 and 5, 2 and 6, and 3 and 5 are more frequent than genome average (Z-test, P < 0.05). The frequencies of gene conversion on the same chromosome decreased with the physical distance between gene conversion partners. Ka/Ks analysis indicates that gene conversion is not tightly linked to natural selection in the rice genome. To assess the contribution of segmental duplication on gene conversion statistics, we determined locations of conversion partners with respect to inter-chromosomal segment duplication. The number of conversions associated with segmentation is less than ten percent. Pseudogenes in the rice genome with low similarity to <it>Arabidopsis </it>genes showed greater likelihood for gene conversion than those with high similarity to <it>Arabidopsis </it>genes. Functional annotations suggest that at least 14 multigene families related to disease or bacteria resistance were involved in conversion events.</p> <p>Conclusion</p> <p>The evolution of gene families in the rice genome may have been accelerated by conversion with pseudogenes. Our analysis suggests a possible role for gene conversion in the evolution of pathogen-response genes.</p

Pembentukan 8-OHdG Dari Zat Toksik Pemicu Radikal Bebas

This study was conducted to observethe profile of DNA Adduct (8-OHdG) formation as DNA damage indicators, by using calf thymus DNA incubated with toxic and carcinogenic compounds. The compounds which could trigger free radicals in this research were PAH(Benzo[a]Pyrene), TiO2, and CuCl2. Calf thymus DNA was incubated with Benzo[a]Pyrene and CuCl2 compounds under pH and temperature variations. The incubation of calf thymus DNA with TiO2-UV radiation (254 nm) wasused to induce the formation of reactive oxygen species (ROS) in the process of oxidative DNA damage. From this research, all of compounds have potency to trigger the formation of DNA Adduct (8-OHdG). The ratio of absorbance to assess the purity of DNA at 260 nm and 280 nm (λ260/ λ280 ) was measured at ~1.9. The shifted peaks at λmax were indicating changes on structures of DNA as a result of calf thymus DNA incubation with B[a]P and CuCl2. The highest level of 8-OHdG results in calf thymus DNA incubation with B[a]P and CuCl2 under pH 8.5 and incubation temperature at 60°C, was about 120.856 μg/L. Calf thymus DNA incubation with TiO2-UV radiation (254 nm) under pH 8.5 resulting 8-OHdG level at 57.025 μg/L

Identification and characterization of insect-specific proteins by genome data analysis

Background: Insects constitute the vast majority of known species with their importance including biodiversity, agricultural, and human health concerns. It is likely that the successful adaptation of the Insecta clade depends on specific components in its proteome that give rise to specialized features. However, proteome determination is an intensive undertaking. Here we present results from a computational method that uses genome analysis to characterize insect and eukaryote proteomes as an approximation complementary to experimental approaches. Results: Homologs in common to Drosophila melanogaster, Anopheles gambiae, Bombyx mori, Tribolium castaneum, and Apis mellifera were compared to the complete genomes of three non-insect eukaryotes (opisthokonts) Homo sapiens, Caenorhabditis elegans and Saccharomyces cerevisiae. This operation yielded 154 groups of orthologous proteins in Drosophila to be insect-specific homologs; 466 groups were determined to be common to eukaryotes (represented by three opisthokonts). ESTs from the hemimetabolous insect Locust migratoria were also considered in order to approximate their corresponding genes in the insect-specific homologs. Stress and stimulus response proteins were found to constitute a higher fraction in the insect-specific homologs than in the homologs common to eukaryotes. Conclusion: The significant representation of stress response and stimulus response proteins in proteins determined to be insect-specific, along with specific cuticle and pheromone/odorant binding proteins, suggest that communication and adaptation to environments may distinguish insect evolution relative to other eukaryotes. The tendency for low Ka/Ks ratios in the insect-specific protein set suggests purifying selection pressure. The generally larger number of paralogs in the insect-specific proteins may indicate adaptation to environment changes. Instances in our insect-specific protein set have been arrived at through experiments reported in the literature, supporting the accuracy of our approach