The Modular Adaptive Ribosome

The ribosome is an ancient machine, performing the same function across organisms. Although functionally unitary, recent experiments suggest specialized roles for some ribosomal proteins. Our central thesis is that ribosomal proteins function in a modular fashion to decode genetic information in a context dependent manner. We show through large data analyses that although many ribosomal proteins are essential with consistent effect on growth in different conditions in yeast and similar expression across cell and tissue types in mice and humans, some ribosomal proteins are used in an environment specific manner. The latter set of variable ribosomal proteins further function in a coordinated manner forming modules, which are adapted to different environmental cues in different organisms. We show that these environment specific modules of ribosomal proteins in yeast have differential genetic interactions with other pathways and their 5’UTRs show differential signatures of selection in yeast strains, presumably to facilitate adaptation. Similarly, we show that in higher metazoans such as mice and humans, different modules of ribosomal proteins are expressed in different cell types and tissues. A clear example is nervous tissue that uses a ribosomal protein module distinct from the rest of the tissues in both mice and humans. Our results suggest a novel stratification of ribosomal proteins that could have played a role in adaptation, presumably to optimize translation for adaptation to diverse ecological niches and tissue microenvironments.     

Effects of a 3-alkyl-, 4-hydroxy- and/or 8-aromatic-substituent on the phenylethanolamine N-methyltransferase inhibitor potency and alpha2-adrenoceptor affinity of 2,3,4,5-tetrahydro-1H-2-benzazepines

2,3,4,5-Tetrahydro-1H-2-benzazepine (THBA; 1) is nearly 100-fold more selective an inhibitor of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) versus the alpha2-adrenoceptor than is 1,2,3,4-tetrahydroisoquinoline (THIQ; 2) (1: PNMT K(i)= 3.3 microM, alpha2-adrenoceptor K(i) = 11 microM, selectivity [alpha2 K(i)/PNMT K(i)] = 3.3; 2: PNMT K(i) = 9.7 microM, alpha2 K(i) = 0.35 microM, selectivity=0.036;). Since the PNMT inhibitory activity and selectivity of THIQ were enhanced by the introduction of a hydrophilic electron-withdrawing 7-substituent and a 3-alkyl-substituent, a similar study was conducted on THBA. 8-Nitro-THBA (3) was found to be as potent an inhibitor of PNMT as its THIQ analogue (21) and to be more selective due to its reduced alpha2-adrenoceptor affinity (3: PNMT K(i) = 0.39 microM, alpha2 K(i) = 66 microM, selectivity = 170; 21: PNMT K(i) = 0.41 microM, alpha2 K(i) = 4.3 microM, selectivity = 10). Introduction of a 3-alkyl substituent on the THBA nucleus decreased both the alpha2-adrenoceptor affinity and the PNMT inhibitory activity, suggesting an area of steric bulk intolerance at both sites. 4-Hydroxy-THBA (15), which can be considered a conformationally-restricted analogue of 3-hydroxymethyl-THIQ (30), exhibited poorer PNMT inhibitory activity and less selectivity than 30 (15: PNMT K(i) = 58 microM, alpha2 K(i) = 100 microM, selectivity = 1.7; 30: PNMT K(i) = 1.1 microM, alpha2 K(i) = 6.6 microM, selectivity = 6.0). While the addition of an 8-nitro group to 15 increased the selectivity of 16 as compared to its THIQ analogue (31), it was not as potent at PNMT nor as selective as 8-nitro-THBA (3) (16, PNMT K(i) = 5.3 microM, alpha2 K(i) = 680 microM, selectivity = 130; 31: PNMT K(i) = 0.29 microM, alpha2 K(i) = 19 microM, selectivity = 66). Compound 3 is the most selective (PNMT/alpha2) and one of the more potent at PNMT compounds yet reported in the benzazepine series, and should have sufficient lipophilicity to penetrate the blood-brain barrier (CLogP = 1.8).     

Pethia sanjaymoluri,a new species of barb (Teleostei: Cyprinidae) from the northern Western Ghats,India

Pethia sanjaymoluri, a new cyprinid, is described from the Pavana and Nira tributaries of Bhima River, Krishna drainage, Maharashtra, India. It can be distinguished from congeners by a combination of characteristics that includes an incomplete lateral line, absence of barbels, upper lip thick and fleshy, 23–25 lateral series scales, 7–12 lateral‐line pored scales, 10 predorsal scales, 11–14 prepelvic scales, 17–20 pre‐anal scales, 4½ scales between dorsal‐fin origin and lateral line, four scales between lateral line and pelvic‐fin origin, 8–15 pairs of serrae on distal half of dorsal‐fin spine, 12–14 branched pectoral‐fin rays, 4 + 26 total vertebrae, 4 + 5 predorsal vertebrae, 4 + 13 abdominal vertebrae, 13 caudal vertebrae and a unique colour pattern comprising a humeral spot positioned below the lateral line and encompassing the third and fourth lateral‐line scales and one scale below, one caudal spot on 17th–21st lateral‐line scales with a yellow hue on its anterior side and apical half of dorsal fin studded with melanophores making the fin tip appear black. Genetic analysis based on the mitochondrial cytochrome b gene sequence suggests that the species is distinct from other known species of Pethia for which data are available.     

Morphological and Genetic variations in the natural populations of Carinotetraodon travancoricus

Carinotetraodon travancoricus or Malabar puffer fish is an endemic species described from rivers originating from the Western Ghats in South India. This species is captured extensively as an aquarium fish and is having substantial demand in global markets. However, being prone to overfishing and impacts of anthropogenic alterations in its habitats, IUCN has categorized it as a threatened/vulnerable species. Since, knowledge on variability of wild populations could help in their conservation and management, morphometric and genotypic analyses were carried out in natural populations of C. travancoricus inhabiting two geographically separated rivers Pamba and Chalakkudy. Mean values of eleven length parameters measured in 456 males and 439 females inhabiting these rivers revealed significant difference (ANOVA, F = 10.2 p < .001) between sexes and between females inhabiting two rivers. Principal component analysis revealed two factors in males and three factors in females, explained variance of 83.62% and 89.94% in respective sexes. Results of both PCA and discriminant function analysis indicated perceptibly high degree of separation between individuals inhabiting the two rivers. A total of 25 COI sequences were generated from C. travancoricus collected from rivers Pamba (n = 14) and Chalakkudy (n = 11). Sequence alignment revealed considerable base substitutions between samples from both rivers, indicating possibility of population differences. AMOVA analysis also provided significant Fst value (0.622; p-value .00) in support of population difference between individuals of both rivers. Interpopulation genetic distance reached upto 2.50%, high enough to confirm genetic diversity among individuals, revealing perceptible population events within this species. The present results indicated high degree of population difference between C. travancoricus inhabiting geographically separated rivers Pamba and Chalakkudy as evidenced from both morphometric and genotypic analyses.     

Isolation and characterization of genomic microsatellite markers for small cardamom (<Emphasis Type="Italic">Elettaria cardamomum</Emphasis> Maton) for utility in genetic diversity analysis

Microsatellite markers in small cardamom (Elettaria cardamomum Maton) were developed using the selective hybridization enrichment method. A total of 140 microsatellite repeats were identified from 270 clones. Primers were designed for 58 microsatellites and 44 primer pairs amplified products of expected size in cardamom. These markers were used for studying the diversity of 20 important small cardamom genotypes, and six markers were found to be polymorphic. The number of alleles ranged from 2 to 7 with an average of 3.6 per locus. Polymorphic information content values ranged from 0.14 to 0.38 based on dominant scoring. The two markers ECM 47a and ECMG 28 generated specific banding patterns for the genotypes MCC7 (Pink tiller) and APG434 (MA18) respectively. Dendrogram illustrated the genetic similarity between different genotypes of Kerala and Karnataka regions. It differentiated the closely related genotypes and released varieties into separate groups. Principal coordinate analysis revealed PV1 and ICRI 1 as the most divergent genotypes. The study demonstrated that these markers are informative and can be further utilized for generating reliable molecular data for assisting the crop improvement of small cardamom. Cross generic transferability (71.4 %) of the developed primers proved that they are useful for phylogenetic studies in the family Zingiberaceae. This is the first report of de novo isolation, characterisation and utilization of microsatellite markers for the genetic diversity analysis of small cardamom.     

On elongation factor eEFSec,its role and mechanism during selenium incorporation into nascent selenoproteins

Background

Selenium, an essential dietary micronutrient, is incorporated into proteins as the amino acid selenocysteine (Sec) in response to in-frame UGA codons. Complex machinery ensures accurate recoding of Sec codons in higher organisms. A specialized elongation factor eEFSec is central to the process.