COVID-19 has effectively spread worldwide. As of May 2020, Turkey is 3 among the top ten countries with the most cases. A comprehensive genomic 4 characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a 5 phylogenetic tree with 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-6 CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in 7 comparison with the previously annotated classifications. We performed a phylogenetic 8 analysis of the first thirty SARS-CoV-2 genomes isolated and sequenced in Turkey. Our 9 results suggest that the first introduction of the virus to the country is earlier than the first 10 reported case of infection. Virus genomes isolated from Turkey are dispersed among most 11 types in the phylogenetic tree. Two of the seventeen sub-clusters were found enriched 12 with the isolates of Turkey, which likely have spread expansively in the country. Finally, 13 we traced virus genomes based on their phylogenetic placements. This analysis suggested 14 multiple independent international introductions of the virus and revealed a hub for the 15 inland transmission. We released a web application to track the global and interprovincial 16 virus spread of the isolates from Turkey in comparison to thousands of genomes 17 worldwide. 18 19 20 24 SARS-CoV genome, the reason behind it's pandemic behaviour is still unclear. Genome 25 sequences around the world were revealed and deposited into public databases such as 26 GISAID (Shu and McCauley 2017). It is crucial to reveal the evolutionary events of 27 SARS-CoV-2 to understand the types of the circulating genomes as well as in which parts 28 of the genome differ across these types. 29 30 The SARS-CoV-2 virus originated from SARS-CoV, and the intermediate versions 31 between two human viruses were found in bats and pangolins (Li, et al. 2020). The virus 32 has been under a strong purifying selection (Li, et al. 2020). With the genomes obtained 33 so far, the sequences of SARS-CoV-2 genomes showed more than 99.9% percent identity 34 suggesting a recent shift to the human species (Tang, et al. 2020). Still, there are clear 35 evolutionary clusters in the genome pool. Various studies use different methods such as 36 SNP based (Tang, et al. 2020) or entropy (Zhao, et al. 2020) based to identify evolving 37 virus strains to reveal genomic regions responsible for transmission and evolution of the 38 virus. Tang et. al identified S and L strains among 103 SARS-CoV-2 genomes based on 39 two SNPs at ORF1ab and ORF8 regions which encode replicase/transcriptase and ATF6, 40 respectively (Tang, et al. 2020). Entropy-based approach generated informative subtype 41 markers from 17 informative positions to cluster evolving virus genomes (Zhao, et al.42 2020). Another study defined a competitive subtype based on D614G mutation at spike 43 59 2.1. Data retrieval, multiple sequence alignment and phylogenomic tree 60 generation 61The entire SARS-CoV-2 genome sequences, along with their metadata were retriev...

COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first 30 SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find 2 of the seventeen subclusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.

Drosophila melanogaster has been extensively used as a model system to study ionizing radiation and chemical-induced mutagenesis, double-strand break repair, and recombination. However, there are only limited studies on nucleotide excision repair in this important model organism. An early study reported that Drosophila lacks the transcription-coupled repair (TCR) form of nucleotide excision repair. This conclusion was seemingly supported by the Drosophila genome sequencing project, which revealed that Drosophila lacks a homolog to CSB, which is known to be required for TCR in mammals and yeasts. However, by using excision repair sequencing (XR-seq) genome-wide repair mapping technology, we recently found that the Drosophila S2 cell line performs TCR comparable to human cells. Here, we have extended this work to Drosophila at all its developmental stages. We find TCR takes place throughout the life cycle of the organism. Moreover, we find that in contrast to humans and other multicellular organisms previously studied, the XPC repair factor is required for both global and transcription-coupled repair in Drosophila.

G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (Gs, Gi, Gq, and G12/13), selectively. However, G protein selective activation mechanisms and residual determinants in GPCRs have remained obscure. Herein, we performed extensive phylogenetic analysis and identified specifically conserved residues for the aminergic receptors having similar coupling profiles. By integrating our methodology of differential evolutionary conservation of G protein–specific amino acids with structural analyses, we identified specific activation networks for Gs, Gi1, Go, and Gq. To validate that these networks could determine coupling selectivity we further analyzed Gs-specific activation network and its association with Gs selectivity. Through molecular dynamics simulations, we showed that previously uncharacterized Glycine at position 7x41 plays an important role in receptor activation and it may determine Gs coupling selectivity by facilitating a larger TM6 movement. Finally, we gathered our results into a comprehensive model of G protein selectivity called “sequential switches of activation” describing three main molecular switches controlling GPCR activation: ligand binding, G protein selective activation mechanisms, and G protein contact.

Major Depressive Disorder (MDD) is a commonly observed psychiatric disorder that affects more than 2% of the world population with a rising trend. However, disease-associated pathways and biomarkers are yet to be fully comprehended. In this study, we analyzed previously generated RNA-seq data across seven different brain regions from three distinct studies to identify differentially and co-expressed genes for patients with MDD. Differential gene expression (DGE) analysis revealed that NPAS4 is the only gene downregulated in three different brain regions. Furthermore, co-expressing gene modules responsible for glutamatergic signaling are negatively enriched in these regions. We used the results of both DGE and co-expression analyses to construct a novel MDD-associated pathway. In our model, we propose that disruption in glutamatergic signaling-related pathways might be associated with the downregulation of NPAS4 and many other immediate-early genes (IEGs) that control synaptic plasticity. In addition to DGE analysis, we identified the relative importance of KEGG pathways in discriminating MDD phenotype using a machine learning-based approach. We anticipate that our study will open doors to developing better therapeutic approaches targeting glutamatergic receptors in the treatment of MDD.