Analysis of codon usage bias of lumpy skin disease virus causing livestock infection.

Lumpy skin disease virus (LSDV) causes lumpy skin disease (LSD) in livestock, which is a double-stranded DNA virus that belongs to the genus Capripoxvirus of the family Poxviridae. LSDV is an important poxvirus that has spread out far and wide to become distributed worldwide. It poses serious health risks to the host and causes considerable negative socioeconomic impact on farmers financially and on cattle by causing ruminant-related diseases. Previous studies explained the population structure of the LSDV within the evolutionary time scale and adaptive evolution. However, it is still unknown and remains enigmatic as to how synonymous codons are used by the LSDV. Here, we used 53 LSDV strains and applied the codon usage bias (CUB) analysis to them. Both the base content and the relative synonymous codon usage (RSCU) analysis revealed that the AT-ended codons were more frequently used in the genome of LSDV. Further low codon usage bias was calculated from the effective number of codons (ENC) value. The neutrality plot analysis suggested that the dominant factor of natural selection played a role in the structuring of CUB in LSDV. Additionally, the results from a comparative analysis suggested that the LSDV has adapted host-specific codon usage patterns to sustain successful replication and transmission chains within hosts (Bos taurus and Homo sapiens). Both natural selection and mutational pressure have an impact on the codon usage patterns of the protein-coding genes in LSDV. This study is important because it has characterized the codon usage pattern in the LSDV genomes and has provided the necessary data for a basic evolutionary study on them.

Structural Evaluation and Conformational Dynamics of ZNF141T474I Mutation Provoking Postaxial Polydactyly Type A.

Postaxial Polydactyly (PAP) is a congenital disorder of limb abnormalities characterized by posterior extra digits. Mutations in the N-terminal region of the Zinc finger protein 141 (ZNF141) gene were recently linked with PAP type A. Zinc finger proteins exhibit similarity at their N-terminal regions due to C2-H2 type Zinc finger domains, but their functional preferences vary significantly by the binding patterns of DNA. Methods: This study delineates the pathogenic association, miss-fold aggregation, and conformational paradigm of a missense variant (c.1420C > T; p.T474I) in ZNF141 gene segregating PAP through a molecular dynamics simulations approach. Results: In ZNF141 protein, helices play a crucial role by attaching three specific target DNA base pairs. In ZNF141T474I protein, H1, H3, and H6 helices attain more flexibility by acquiring loop conformation. The outward disposition of the proximal portion of H9-helix in mutant protein occurs due to the loss of prior beta-hairpins at the C terminal region of the C2-H2 domain. The loss of hydrogen bonds and exposure of hydrophobic residues to solvent and helices turning to loops cause dysfunction of ZNF141 protein. These significant changes in the stability and conformation of the mutant protein were validated using essential dynamics and cross-correlation maps, which revealed that upon point mutation, the overall motion of the proteins and the correlation between them were completely different, resulting in Postaxial polydactyly type A. Conclusions: This study provides molecular insights into the structural association of ZNF141 protein with PAP type A. Identification of active site residues and legends offers new therapeutic targets for ZNF141 protein. Further, it reiterates the functional importance of the last residue of a protein.

A detailed comparative analysis of codon usage bias in Alongshan virus.

Alongshan virus (ALSV) is an emerging tick-borne pathogen that infects humans, causing febrile disease. ALSV uses Ixodes Persulcatus ticks to infect humans with a wide range of signs, from asymptomatic to encephalitis-like syndrome. There is an increasing public health concern about the ALSV infection. To get insight into the impacts of viral relations with their hosts on viral ability, survival, and evasion from hosts immune systems remain unknown. The codon usage is a driving force in viral genome evolution; therefore, we enrolled 41 ALSV strains in codon usage analysis to elucidate the molecular evolutionary dynamics of ALSV. The results indicate that the overall codon usage among ALSV isolates is relatively similar and slightly biased. Base compositions for the cds were in order of G >A >C >U and in the third position of codons G3 >A3 >C3 >T3. The RSCU values revealed that the more frequently used codons were mostly GC ended. Different codon preferences in ALSV genes in relation to codon usage of H. sapiens and Ixodes Persulcatus genes were found. Neutrality plot was determined to reveal the superiority of natural selection over directional mutation pressure in causing CUB based on GC12 versus GC3 contents. The results of these studies suggest that the emergence of ALSV in China, Russia and Finland may also be reflected in ALSV codon usage. Altogether, the presence of both mutation pressure and natural selection effect in shaping the codon usage patterns of ALSV.

Ethylene Regulates Levels of Ethylene Receptor/CTR1 Signaling Complexes in Arabidopsis thaliana.

The plant hormone ethylene is perceived by a five-member family of receptors in Arabidopsis thaliana. The receptors function in conjunction with the Raf-like kinase CTR1 to negatively regulate ethylene signal transduction. CTR1 interacts with multiple members of the receptor family based on co-purification analysis, interacting more strongly with receptors containing a receiver domain. Levels of membrane-associated CTR1 vary in response to ethylene, doing so in a post-transcriptional manner that correlates with ethylene-mediated changes in levels of the ethylene receptors ERS1, ERS2, EIN4, and ETR2. Interactions between CTR1 and the receptor ETR1 protect ETR1 from ethylene-induced turnover. Kinetic and dose-response analyses support a model in which two opposing factors control levels of the ethylene receptor/CTR1 complexes. Ethylene stimulates the production of new complexes largely through transcriptional induction of the receptors. However, ethylene also induces turnover of receptors, such that levels of ethylene receptor/CTR1 complexes decrease at higher ethylene concentrations. Implications of this model for ethylene signaling are discussed.

Was low CO2 a driving force of C4 evolution: Arabidopsis responses to long-term low CO2 stress.

The responses of long-term growth of plants under elevated CO2 have been studied extensively. Comparatively, the responses of plants to subambient CO2 concentrations have not been well studied. This study aims to investigate the responses of the model C3 plant, Arabidopsis thaliana, to low CO2 at the molecular level. Results showed that low CO2 dramatically decreased biomass productivity, together with delayed flowering and increased stomatal density. Furthermore, alteration of thylakoid stacking in both bundle sheath and mesophyll cells, upregulation of PEPC and PEPC-K together with altered expression of a number of regulators known involved in photosynthesis development were observed. These responses to low CO2 are discussed with regard to the fitness of C3 plants under low CO2. This work also briefly discusses the relevance of the data to C4 photosynthesis evolution.

Ecotypic variation in chloroplast small heat-shock proteins and related thermotolerance in Chenopodium album.

Production of chloroplast-localized small heat-shock proteins (Cp-sHSP) is correlated with increased thermotolerance in plants. Ecotypic variation in function and expression of Cp-sHSPs was analyzed in two Chenopodium album ecotypes from cool vs. warm-temperate USA habitats [New York (NY) and Mississippi (MS) respectively]. P(et) was more heat tolerant in the MS than the NY ecotype, and MS ecotype derived proportionally greater protection of P(et) by Cp-sHSP during high temperatures. Four genes encoding Cp-sHSPs were isolated and characterized: CaHSP25.99n (NY-1) and CaHSP26.23n (NY-2) from NY ecotype, and CaHSP26.04m (MS-1) and CaHSP26.26m (MS-2) from MS ecotype. The genes were nearly identical in predicted amino-acid sequence and hydrophobicity. Gene expression analysis indicated that MS-1 and MS-2 transcripts were constitutively expressed at low levels at 25 °C, while no NY-1 and NY-2 transcripts were detected at this temperature. Maximum accumulation of NY-1 and NY-2 transcripts occurred at 33 °C and 40 °C for MS-1 and MS-2. Immunoblot analysis revealed that (1) protein expression was highest at 37 °C in both ecotypes, but was greater in MS than NY ecotype at 40 °C; and (2) import of Cp-sHSP into chloroplasts was more heat-labile in NY ecotype. The higher expression of one isoform in MS ecotype may contribute to its enhanced thermotolerance. Absence of correlation between protein and transcript levels, suggests the post-transcriptional regulation is occurring. Promoter analysis of these genes revealed significant variations in heat-shock elements (HSE), core motifs required for heat-shock-factor binding. We propose a correlation between unique promoter architecture, Cp-sHSP expression and thermotolerance in both ecotypes.