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Abstract Background Human accelerated regions (HARs) are short conserved genomic sequences that have acquired significantly more nucleotide substitutions than expected in the human lineage after divergence from chimpanzees. The fast evolution of HARs may reflect their roles in the origin of human-specific traits. A recent study has reported positively-selected single nucleotide variants (SNVs) within brain-exclusive human accelerated enhancers (BE-HAEs) hs1210 (forebrain), hs563 (hindbrain) and hs304 (midbrain/forebrain). By including data from archaic hominins, these SNVs were shown to be Homo sapiens-specific, residing within transcriptional factors binding sites (TFBSs) for SOX2 (hs1210), RUNX1/3 (hs563), and FOS/JUND (hs304). Although these findings suggest that the predicted modifications in TFBSs may have some role in present-day brain structure, work is required to verify the extent to which these changes translate into functional variation. Results To start to fill this gap, we investigate the SOX2 SNV, with both forebrain expression and strong signal of positive selection in humans. We demonstrate that the HMG box of SOX2 binds in vitro with Homo sapiens-specific derived A-allele and ancestral T-allele carrying DNA sites in BE-HAE hs1210. Molecular docking and simulation analysis indicated highly favourable binding of HMG box with derived A-allele containing DNA site when compared to site carrying ancestral T-allele. Conclusion These results suggest that adoptive changes in TF affinity within BE-HAE hs1210 and other HAR enhancers in the evolutionary history of Homo sapiens might have brought about changes in gene expression patterns and have functional consequences on forebrain formation and evolution. Methods The present study employ electrophoretic mobility shift assays (EMSA) and molecular docking and molecular dynamics simulations approaches.

Objective: To check which of the eight pro-hypertrophic transcription factors bind in abundance to a set of 140 functionally confirmed cardiac enhancers aiming to identify potential therapeutic targets for delaying the onset of cardiac hypertrophy. Study Design: Bioinformatics, in-Silico Study. Place and Duration of Study: The study was conducted at the Department of Biological Sciences, National University of Medical Sciences (NUMS), Rawalpindi, Pakistan, from January 2022 to December 2022. Methods: For experimentally verified human and mouse noncoding regions with gene enhancer activity measured in transgenic mice, VISTA Enhancer Browser was used to obtain 140 cardiac-specific functionally confirmed enhancers. Among these enhancers, transcription factor binding sites were computationally mapped to assess transcription factor occupancy. The binding sites for all eight transcription factors were screened in the collective set of 140 cardiac enhancers via an in-house script. Results: In this study, among a small set of eight pro-hypertrophic transcription factors, occupancy of transcription factor HAND (Heart- And Neural Crest Derivatives-Expressed Protein) was found to be maximum in the collected pool of functionally confirmed cardiac enhancers. Conclusion: The transcription factor HAND was found to have maximum binding occupancy among a set of experimentally confirmed cardiac enhancers. How to cite this: Raza RZ, Hussain I, Akhtar F, Mumtaz S. The Binding Occupancy of Pro-Hypertrophic Transcription Factors among Cardiac Developmental Enhancers. Life and Science. 2024; 5(1): 22-26. doi: http://doi.org/10.37185/LnS.1.1.464

The ongoing pandemic of COVID-19 has elaborated an idiosyncratic pattern of SARS-CoV-2-induced symptoms in the human host. Some populations have succumbed to the SARS-CoV-2 infection in large numbers during this pandemic, whereas others have shown a resilient side by manifesting only milder or no symptoms at all. This observation has relayed the onus of the heterogeneous pattern of SARS-CoV-2-induced critical illness among different populations to the host genetic factors. Here, the evolutionary route was explored and three genetic loci, i.e., rs10735079, rs2109069, and rs2236757, associated with COVID-19 were analyzed. Among the three, the risk allele A at genetic locus rs2236757 residing in the IFNAR2 gene was observed to have undergone recent positive selection in the African population.