Adipose Lipolysis Regulates Cardiac Glucose Uptake and Function in Mice under Cold Stress

The heart primarily uses fatty acids as energy substrates. Adipose lipolysis is a major source of fatty acids, particularly under stress conditions. In this study, we showed that mice with selective inactivation of the lipolytic coactivator comparative gene identification-58 (CGI-58) in adipose tissue (FAT-KO mice), relative to their littermate controls, had lower circulating FA levels in the fed and fasted states due to impaired adipose lipolysis. They preferentially utilized carbohydrates as energy fuels and were more insulin sensitive and glucose tolerant. Under cold stress, FAT-KO versus control mice had >10-fold increases in glucose uptake in the hearts but no increases in other tissues examined. Plasma concentrations of atrial natriuretic peptide and cardiac mRNAs for atrial and brain-type natriuretic peptides, two sensitive markers of cardiac remodeling, were also elevated. After one week of cold exposure, FAT-KO mice showed reduced cardiac expression of several mitochondrial oxidative phosphorylation proteins. After one month of cold exposure, hearts of these animals showed depressed functions, reduced SERCA2 protein, and increased proteins for MHC-β, collagen I proteins, Glut1, Glut4 and phospho-AMPK. Thus, CGI-58-dependent adipose lipolysis critically regulates cardiac metabolism and function, especially during cold adaptation. The adipose-heart axis may be targeted for the management of cardiac dysfunction.

Delineating the elusive BaMMV resistance gene rym15 in barley by medium-resolution mapping

Barley mild mosaic virus (BaMMV), transmitted by the soil-borne protist Polymyxa graminis, has a serious impact on winter barley production. Previously, the BaMMV resistance gene rym15 was mapped on chromosome 6HS, but the order of flanking markers was non-collinear between different maps. To resolve the position of the flanking markers and to enable map-based cloning of rym15, two medium-resolution mapping populations Igri (susceptible) × Chikurin Ibaraki 1 (resistant) (I × C) and Chikurin Ibaraki 1 × Uschi (susceptible) (C × U), consisting of 342 and 180 F2 plants, respectively, were developed. Efficiency of the mechanical inoculation of susceptible standards varied from 87.5 to 100% and in F2 populations from 90.56 to 93.23%. Phenotyping of F2 plants and corresponding F3 families revealed segregation ratios of 250 s:92r (I × C, χ2 = 0.659) and 140 s:40r (C × U, χ2 = 0.741), suggesting the presence of a single recessive resistance gene. After screening the parents with the 50 K Infinium chip and anchoring corresponding SNPs to the barley reference genome, 8 KASP assays were developed and used to remap the gene. Newly constructed maps revealed a collinear order of markers, thereby allowing the identification of high throughput flanking markers. This study demonstrates how construction of medium-resolution mapping populations in combination with robust phenotyping can efficiently resolve conflicting marker ordering and reduce the size of the target interval. In the reference genome era and genome-wide genotyping era, medium-resolution mapping will help accelerate candidate gene identification for traits where phenotyping is difficult.

Pattern of New Gene Origination in a Special Fish Lineage, the Flatfishes

Origination of new genes are of inherent interest of evolutionary geneticists for decades, but few studies have addressed the general pattern in a fish lineage. Using our recent released whole genome data of flatfishes, which evolved one of the most specialized body plans in vertebrates, we identified 1541 (6.9% of the starry flounder genes) flatfish-lineage-specific genes. The origination pattern of these flatfish new genes is largely similar to those observed in other vertebrates, as shown by the proportion of DNA-mediated duplication (1317; 85.5%), RNA-mediated duplication (retrogenes; 96; 6.2%), and de novo–origination (128; 8.3%). The emergence rate of species-specific genes is 32.1 per Mya and the whole average level rate for the flatfish-lineage-specific genes is 20.9 per Mya. A large proportion (31.4%) of these new genes have been subjected to selection, in contrast to the 4.0% in primates, while the old genes remain quite similar (66.4% vs. 65.0%). In addition, most of these new genes (70.8%) are found to be expressed, indicating their functionality. This study not only presents one example of systematic new gene identification in a teleost taxon based on comprehensive phylogenomic data, but also shows that new genes may play roles in body planning.

CORSID enables de novo identification of transcription regulatory sequences and genes in coronaviruses

Genes in coronaviruses are preceded by transcription regulatory sequences (TRSs), which play a critical role in gene expression mediated by the viral RNA-dependent RNA-polymerase via the process of discontinuous transcription. In addition to being crucial for our understanding of the regulation and expression of coronavirus genes, we demonstrate for the first time how TRSs can be leveraged to identify gene locations in the coronavirus genome. To that end, we formulate the TRS AND GENE IDENTIFICATION (TRS-GENE-ID) problem of simultaneously identifying TRS sites and gene locations in unannotated coronavirus genomes. We introduce CORSID (CORe Sequence IDentifier), a computational tool to solve this problem. We also present CORSID-A, which solves a constrained version of the TRS-GENE-ID problem, the TRS IDENTIFICATION (TRS-ID) problem, identifying TRS sites in a coronavirus genome with specified gene annotations. We show that CORSID-A outperforms existing motif-based methods in identifying TRS sites in coronaviruses and that CORSID outperforms state-of-the-art gene finding methods in finding genes in coronavirus genomes. We demonstrate that CORSID enables de novo identification of TRS sites and genes in previously unannotated coronaviruses. CORSID is the first method to perform accurate and simultaneous identification of TRS sites and genes in coronavirus genomes without the use of any prior information.

Functional Gene Identification and Corresponding Tolerant Mechanism of High Furfural-Tolerant Zymomonas mobilis Strain F211

Furfural is a major inhibitor in lignocellulose hydrolysate for Zymomonas mobilis. A mutant F211 strain with high furfural tolerance was obtained from our previous study. Thus, its key tolerance mechanism was studied in the present study. The function of mutated genes in F211 was identified by functional complementation experiments, revealing that the improved furfural tolerance was resulted from the C493T mutation of the ZCP4_0270 gene promoting cell flocculation and the mutation (G1075A)/downregulation of ZCP4_0970. Comparative transcriptome analysis revealed 139 differentially expressed genes between F211 and the control, CP4, in response to furfural stress. In addition, the reliability of the RNA-Seq data was also confirmed. The potential tolerance mechanism was further demonstrated by functional identification of tolerance genes as follows: (I) some upregulated or downregulated genes increase the levels of NAD(P)H, which is involved in the reduction of furfural to less toxic furfuryl alcohol, thus accelerating the detoxification of furfural; (II) the mutated ZCP4_0270 and upregulated cellulose synthetase gene (ZCP4_0241 and ZCP4_0242) increased flocculation to resist furfural stress; (III) upregulated molecular chaperone genes promote protein synthesis and repair stress-damaged proteins; and (IV) transporter genes ZCP4_1623–1,625 and ZCP4_1702–1703 were downregulated, saving energy for cell growth. The furfural-tolerant mechanism and corresponding functional genes were revealed, which provides a theoretical basis for developing robust chassis strains for synthetic biology efforts.

Use of Average Mutual Information and Derived Measures to Find Coding Regions

One of the important steps in the annotation of genomes is the identification of regions in the genome which code for proteins. One of the tools used by most annotation approaches is the use of signals extracted from genomic regions that can be used to identify whether the region is a protein coding region. Motivated by the fact that these regions are information bearing structures we propose signals based on measures motivated by the average mutual information for use in this task. We show that these signals can be used to identify coding and noncoding sequences with high accuracy. We also show that these signals are robust across species, phyla, and kingdom and can, therefore, be used in species agnostic genome annotation algorithms for identifying protein coding regions. These in turn could be used for gene identification.

Two Nicotiana occidentalis accessions enable gene identification for Type II hybrid lethality by the cross to N. sylvestris

Hybrid lethality, meaning the death of F1 hybrid seedlings, has been observed in many plant species, including Nicotiana. Previously, we have revealed that hybrids of the selected Nicotiana occidentalis accession and N. tabacum, an allotetraploid with S and T genomes, exhibited lethality characterized by the fading of shoot color. The lethality was suggested to be controlled by alleles of loci on the S and T genomes derived from N. sylvestris and N. tomentosiformis, respectively. Here, we extended the analysis of hybrid lethality using other two accessions of N. occidentalis identified from the five tested accessions. The two accessions were crossed with N. tabacum and its two progenitors, N. sylvestris and N. tomentosiformis. After crosses with N. tabacum, the two N. occidentalis accessions yielded inviable hybrid seedlings whose lethality was characterized by the fading of shoot color, but only the T genome of N. tabacum was responsible for hybrid lethality. Genetic analysis indicated that first-mentioned N. occidentalis accession carries a single gene causing hybrid lethality by allelic interaction with the S genome.