Position-wise mutation analysis and temporal changes in SARS CoV-2 Envelope (E) protein variants Anwesa Saha [1,†] , Diganta Mukherjee [1,†] , Aparna Mukhopadhyay* [1]

https://www.academia.edu/3064-9765/2/4/10.20935/AcadMolBioGen8011 SARS CoV-2 is a positive-sense, single-stranded RNA virus. The genome of the virus undergoes numerous mutations, making the development of universally effective drugs challenging. Among its structural proteins, the Envelope (E) protein acts as an ion transporter and virulence factor, making it a potential therapeutic target. Based on the literature available to date, we have identified several functionally important sites in the E protein. These include residues involved in lysosomal deacidification; those of the FYXY motif, involved in amyloid formation in the host; and the PDZ-binding DLLV motif. We focus our analysis on the significance of these residues while also searching for other interesting mutational patterns. In this study, we conducted a comprehensive mutational analysis of the SARS CoV-2 E protein utilizing bioinformatics, statistics, and structural modeling tools. Over 1.4 million sequences were retrieved from the NCBI virus database, filtered, clustered, and aligned chronologically. By employing a combination of web-based tools and in-house Python scripts, we analyzed per-residue Shannon entropy, mutation types, evolutionary pressure, and predicted structural impact (via ∆∆G). We observed a significant number of residues under diversifying selection. This suggests that new amino acids are being sampled at various positions in the protein, providing functional or structural benefits to the virus. A cyclical pattern of mutation and reversion was observed at position 9, stabilizing at a particular mutation. Similar trends appeared at position 11. These mutations may be functionally relevant, which need to be explored in future. However, the key regions have remained conserved over time. The evolution of cognitive abilities in marine animals: a hypothesis based on insights about cognition gene polymorphisms in Coelocanths and lungfish Zhizhou Zhang* [1], Shuaiyu Zhang [2], Yongdong Xu* [2] https://www.academia.edu/3064-9765/2/4/10.20935/AcadMolBioGen8001 Both coelacanths and lungfish have fossil evidence dating back 400 million years, placing them at a critical evolutionary juncture when marine animals transitioned to terrestrial environments. An intriguing question lies in the extent to which their cognitive abilities had evolved before they crawled onto land. While no fossil DNA exist for extinct coelacanths or lungfish, studies on their extant species offer clues. Notably, the biological traits of coelacanths and lungfish have been remarkably stable over the past 70 million years, suggesting that some genomic regions in their genomic sequences possess exceptional stability. This raises the possibility of inferring their cognition gene polymorphism patterns (CGPPs) and evolutionary positioning through genomic analyses of modern samples. By employing 471 whole-genome sequence samples, including archaic humans (Neanderthals, Denisovans and more), modern humans, other vertebrates (fish, amphibians, reptiles, birds, rodents, mammals) plus four coelacanth and three lungfish samples, together with 18 human cognition-related genes and their total of 223 SNVs (Single-Nucleotide Variations),comparative analyses revealed that the CGPPs of both coelacanths and lungfish are evolutionarily closer to those of archaic humans than those of most other animal groups. The CGPP appears to occupy an evolutionary inflection point, bridging diverse animal lineages to archaic hominoids. Our observational results suggest a hypothesis (to be validated in the future) that the genetic architecture underlying human cognitionseemsto have beenestablished during the evolutionary stage of fish, predating the emergence of tetrapods.