Temperature differences over time and space have been hypothesized to cause variation in the rate of molecular evolution of species, but empirical evidence is mixed. To further test this hypothesis, we utilized a large exon‐capture sequence data of Australian Eugongylinae skinks, exemplifying a radiation of temperature‐sensitive ectotherms spanning a large latitudinal gradient. The association between temperature (and other species traits) and long‐term substitution rate was assessed based on 1268 sequenced exons of 44 species pairs from the Eugongylinae subfamily using regression analyses. Temperature is the strongest, positively correlated predictor of variation in substitution rate across the Australian Eugongylinae. It explains 45% of variation in synonymous substitution rate, and 11% after controlling for all the other factors. Synonymous substitution rate is also negatively associated with body size, with a 6% variation explained by body size after controlling for the effects of temperature. Other factors are not associated with synonymous substitution rate after controlling for temperature. Overall, this study points to temperature as a strong predictor of the molecular evolution rate in the Eugongylinae subfamily, and demonstrates the power of large‐scale exonic data to identify correlates of the rate of molecular evolution.
Inhibition of ADP-ribosylation factor 6 messenger RNA (ARF6 mRNA) by microRNA-145 (miR-145), mediated by Argonaute (AGO) protein, has been found to play essential roles in several types of cancer and cellular processes. This study aimed to model the molecular interaction between miR-145 and ARF6 mRNA with AGO protein. The sequences of miR-145 and the 3’ untranslated region (UTR) of ARF6 mRNA were retrieved from miRTarBase, followed by miRNA target-site and structure predictions were done using RNAhybrid, RNAfold, and simRNAweb, respectively. The interaction between the miRNA-mRNA duplex and AGO was further assessed via molecular docking, interaction analysis, and dynamics, using PatchDock Server, PLIP, and VMD/NAMD, respectively. The models between miR-145, predicted target site of ARF6 mRNA, and AGO protein returned stable thermodynamic variables with negative free energy. Specifically, the RNA duplex had an energy of -19.80 kcal/mol, while the docking had -84.58 atomic contact energy supported by 70 hydrogen bonds and 14 hydrophobic interactions. However, the stability of the RMSD plot was still unclear due to limited computational resources. Nevertheless, these results computationally confirm favorable interaction of the three molecules, which can be utilized for further transcriptomics-based drugs or treatments.
Kemal RA, Sandjaja EBL, Santosa AP, Ivan J. 2018. Short Communication: Identification of Mildew Locus O (MLO) genes in Durio zibethinus genome corresponding with the Powdery Mildew disease. Biodiversitas 19: 2204-2212. Mildew Locus O (MLO) is a protein consisting of seven transmembrane domains and appears in the various type of plants. MLO proteins are classified into seven clades. It is known that specific clades have different roles in a plant. MLOs from Clades IV and V have been linked to plant's susceptibility to Powdery Mildew (PM) disease. This study aimed to provide an overview of MLO genes present in durian (Durio zibethinus) genome. Bioinformatic analyses were conducted to analyze the phylogeny and structure of MLO genes and proteins in durian. The result showed that there were 20 putative DzMLO genes in durian, encoding 39 putative DzMLO proteins. Durian MLOs belong to Clade I-VI with one protein belongs to Clade IV and five proteins belong to Clade V. Those six MLO proteins shared a common motif in C-terminal and second intracellular domains. Putative alternative splicing and differential expressions were observed among Clade V DzMLO genes. These findings will facilitate the functional characterization of MLO genes and proteins in durian. Functional studies, especially on C-terminal and second intracellular domains, need to be conducted to elucidate the role of MLO in PM susceptibility in durian.
Selective inhibitors of CYP isoforms gaining importance in the treatment of cancers caused by hormonal imbalance. Metabolites of estradiol and polyaromatic hydrocarbons generated due to CYP1B1 activity were reported to be oncogenic. The selective CYP1B1 inhibitors could have the potential therapeutic utility in controlling the cancer due to these oncogens. Due to the CYP isoforms high sequence similarity the design of selective CYP inhibitor is difficult. Recently our group has reported two novel chemical classes (scaffolds) that are specific towards CYP1B1. The chemical architecture of these compounds should give valuable information for its selectivity and potency against CYP1B1. Overlay of our compounds and ANF by Shape and electrostatic based similarity and molecular docking displayed different orientations. Moreover the study has shown the overlay of three atom bridge of selective inhibitor superimposed on-O-CHlinking aryl groups rather than-CO-CH=CHof ANF. Molecular docking simulation revealed that the selective inhibitors are either establishing H-bonding interaction with Asp333 or π-π staking interaction Phe231 and Phe268. Molecular docking simulation has provided much more information rather than simple shape and electrostatic based similarity study. Crucial H-bonding interactions and π-π staking interactions responsible for selectivity towards CYP1B1 were identified. Two atom linker between the aryl groups matter, cyclization simply ensures the planarity of ANF and quinazolines.
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