Indian Institute of Technology Gandhinagar

The formation of G-quadruplexes (G4) is fundamentally linked to GC content of the DNA. There is little evidence for evolutionary selection of G4 stabilizers; G4 formation depends strictly on inherent sequence properties. Vertebrate promoters are notable for their consistently high GC-content as well as pronounced G/C strand asymmetry. Genomic GC content has changed in the course of evolution of terrestrial vertebrates, especially the amniotes but its relationship with the potential to form G4 remains less well understood. By analyzing genomes of 101 amniotes we report that lineage-specific differences in association between GC-content and G4 formation potential (pG4) in amniotes are concentrated at 1kb promoter regions. To understand possible mechanisms underlying high GC-concentrations in pG4 of mammalian and avian promoters, we test the possibility of selective cytosine methylation restriction leading to G/C-retention by CGGBP1, a protein involved in mitigation of cytosine methylation as well as G4-formation. By analyzing promoterome-wide C-T transition rates at TFBSs in pG4s we show that mammalian and avian CGGBP1s preserve C through methylation restriction. Our approach involves a combined meta-analysis of (i) genomes and promoters of 101 amniote genomes classified into reptilian, avian and mammalian classes through PQS finder and FIMO for 1019 JASPAR vertebrate motifs, (ii) recently reported global cytosine methylation patterns affected by overexpression of amniotic or non-amniotic forms of CGGBPs, (iii) and PWM reconstruction of motifs differentially enriched in pG4s showing homeothermic specific GC-retention. Our findings suggest that cytosine methylation restriction by CGGBP1 shapes G4 forming profiles of vertebrate promoters by preserving C on the G4-complementary strand resulting in minute differences in TFBSs across amniotes.

General relativity (GR) lays the foundation for successfully explaining the current gravitational wave (GW) observations. We present a method for studying the orbital frequency evolution of GWs from binary black hole (BBH) systems based on their energy distribution on the time-frequency plane. The orbital frequency evolution of BBH systems is determined by the individual masses and spins of the component black holes and the governing gravity theory. If a beyond-GR theory of gravity governs the BBH orbital evolution for the same set of binary parameters, the time-frequency pixel energies will exhibit a different frequency evolution from what is predicted by GR. We develop a new consistency test to check whether GR explains the BBH orbital evolution. Through numerical simulation of beyond-GR theory of gravity, we demonstrate the efficiency of this new method in detecting any possible departure from GR in the framework of second-generation GW interferometers. Further, we discuss the utility of our method in probing missing physics in the GW waveform models. We apply our test to the GW190814 and GW190412 data from the LIGO-Livingston detector, assuming that the analyzing template waveform does not include higher-order modes. The lack of subdominant modes results in an incomplete representation of the GW signal, leading to systematic biases in the frequency evolution of the signal.

Considering a doubly holographic model, we study the evolution of holographic subregion complexity corresponding to deformations of bath state by a relevant scalar operator, which corresponds to a renormalization group flow from the AdS-Schwarzschild to the Kasner universe in the bulk. The subregion complexity shows a discontinuous jump at Page time at a fixed perturbation, where the discontinuity depends solely on the system's parameters. We show that the amount of discontinuity decreases with the perturbation as well as with the scaling dimension of the relevant scalar operator.