Biology subjects

Kaur, T.

Publications and source records attributed to Kaur, T..

23 records · Page 2Linked to original sources

bioRxiv2020

The ancestral C. elegans cuticle suppresses rol-1

Genetic background commonly modifies the effects of mutations. We discovered that worms mutant for the canonical rol-1 gene, identified by Brenner in 1974, do not roll in the genetic background of the wild strain CB4856. Using linkage mapping, association analysis and gene editing, we determined that N2 carries an insertion in the collagen gene col-182 that acts as a recessive enhancer of rol-1 rolling. From population and comparative genomics, we infer the insertion is derived in N2 and related laboratory lines, likely arising during the domestication of Caenorhabditis elegans, and breaking a conserved protein. The ancestral version of col-182 also modifies the phenotypes of four other classical cuticle mutant alleles, and the effects of natural genetic variation on worm shape and locomotion. These results underscore the importance of genetic background and the serendipity of Brenners choice of strain.

genetics↗

bioRxiv2019

A new knockdown resistance (kdr) mutation F1534L in Aedes aegypti associated with insecticide resistance

BackgroundAedes aegypti is a primary vector of dengue, chikungunya and zika infections in India. In the absence of specific drugs or safe and effective vaccines for these infections, their control relies mainly on vector control measures. The emergence of insecticide resistance in vectors, especially against pyrethroids, is a serious threat to the insecticide-based vector control programme. This study reports the presence of multiple knockdown resistance (kdr) mutations present in an Ae. aegypti population from Bengaluru (India), including a new mutation F1534L. MethodsAedes aegypti collected from Bengaluru were subjected to insecticide susceptibility tests with DDT, deltamethrin and permethrin. The DNA sequencing of partial domain II, III and IV of the voltage-gated sodium channel (VGSC) was performed to screen kdr mutations present in the population and PCR-based assays were developed for their detection. Genotyping of kdr mutations was done using PCR-based assays, allelic frequencies were determined, and tests of genetic association of kdr mutations with the insecticide resistance phenotype were performed. ResultsThe Ae. aegypti population were resistant to DDT, deltamethrin and permethrin. The DNA sequencing of the VGSC revealed the presence of four kdr mutations, i.e., S989P and V1016G in domain II and two alternative kdr mutations F1534C and F1534L in domain III. Allele-specific PCR assays (ASPCR) were developed for the detection of kdr mutations S989P and V1016G and an existing PCR-RFLP based strategy was modified for the genotyping of all three known kdr mutations in domain III (F1534L, F1534C and T1520I). Genotyping of Ae. aegypti samples collected between October 2014 and April 2015 revealed a moderate frequency of S989P/V1016G (18.27%) and F1534L (17.48%), a relatively high frequency of F1534C (50.61%) and absence of T1520I in the population. Mutations S989P and V1016G were in complete linkage disequilibrium in this population while they were in linkage equilibrium with kdr mutations F1534C and F1534L. The alleles F1534C and F1534L are genetically associated with permethrin resistance. ConclusionsA new kdr mutation, F1534L, was found in an Ae. aegypti population from Bengaluru (India), co-occurring with the other three mutations S989P, V1016G and F1534C. The findings of a new mutation and development of PCR-based diagnostics have implications for insecticide resistance management. Monitoring of F1534L-kdr in other populations and studies on their functional role in altering neuro-sensitivity is warranted.

molecular biology↗

bioRxiv2019

Interplay Between Short-range Attraction and Long-range Repulsion Controls Reentrant Liquid Condensation of Ribonucleoprotein-RNA Complexes

In eukaryotic cells, ribonucleoproteins (RNPs) form mesoscale condensates by liquid-liquid phase separation that play essential roles in subcellular dynamic compartmentalization. The formation and dissolution of many RNP condensates are finely dependent on the RNA-to-RNP ratio, giving rise to a window-like phase separation behavior. This is commonly referred to as reentrant liquid condensation (RLC). Here, using RNP-inspired polypeptides with low-complexity RNA-binding sequences as well as the C-terminal disordered domain of the ribonucleoprotein FUS as model systems, we investigate the molecular driving forces underlying this non-monotonous phase transition. We show that an interplay between short-range cation-{pi} attractions and long-range electrostatic forces governs the heterotypic RLC of RNP-RNA complexes. Short-range attractions, which can be encoded by both polypeptide chain primary sequence and nucleic acid base sequence, are activated by RNP-RNA condensate formation. After activation, the short-range forces regulate material properties of polypeptide-RNA condensates and subsequently oppose their reentrant dissolution. In the presence of excess RNA, a competition between short-range attraction and long-range electrostatic repulsion drives the formation of a colloid-like cluster phase. With increasing short-range attraction, the fluid dynamics of the cluster phase is arrested, leading to the formation of a colloidal gel. Our results reveal that phase behavior, supramolecular organization, and material states of RNP-RNA assemblies are controlled by a dynamic interplay between molecular interactions at different length scales.

biophysics↗

bioRxiv2018

Molecular Crowding Tunes Material States of Ribonucleoprotein Condensates

Ribonucleoprotein (RNP) granules are membraneless liquid condensates that dynamically form, dissolve, and mature into a gel-like state in response to changing cellular environment. RNP condensation is largely governed by the promiscuous attractive inter-chain interactions, mediated by low-complexity domains (LCDs). Using an archetypal disordered RNP, Fused in Sarcoma (FUS), here we study how molecular crowding impacts the RNP liquid condensation. We observe that the liquid-liquid coexistence boundary of FUS is lowered by polymer crowders, consistent with the excluded volume model. With increasing bulk crowder concentration, RNP partition increases and the diffusion rate decreases in the condensed phase. Furthermore, we show that RNP condensates undergo substantial hardening wherein protein-dense droplets transition from viscous fluid to a viscoelastic gel-like state in a crowder concentration-dependent manner. Utilizing two distinct LCDs that broadly represent the most commonly occurring sequence motifs driving RNP phase transition, we reveal that the impact of crowding is largely independent of LCD charge/sequence patterns. These results are consistent with a thermodynamic model of crowder-mediated depletion interaction where inter-RNP attraction is enhanced by molecular crowding. The depletion force is likely to play key roles in tuning the physical properties of RNP condensates within a crowded intracellular space.

biophysics↗

bioRxiv2018

Comparative genomics of ten new Caenorhabditis species

The nematode Caenorhabditis elegans has been central to the understanding of metazoan biology. However, C. elegans is but one species among millions and the significance of this important model organism will only be fully revealed if it is placed in a rich evolutionary context. Global sampling efforts have led to the discovery of over 50 putative species from the genus Caenorhabditis, many of which await formal species description. Here, we present species descriptions for ten new Caenorhabditis species. We also present draft genome sequences for nine of these new species, along with a transcriptome assembly for one. We exploit these whole-genome data to reconstruct the Caenorhabditis phylogeny and use this phylogenetic tree to dissect the evolution of morphology in the genus. We show unexpected complexity in the evolutionary history of key developmental pathway genes. The genomic data also permit large scale analysis of gene structure, which we find to be highly variable within the genus. These new species and the associated genomic resources will be essential in our attempts to understand the evolutionary origins of the C. elegans model.

evolutionary biology↗