Biology subjects

Selcuk, B.

Publications and source records attributed to Selcuk, B..

5 recordsLinked to original sources

bioRxiv2026

GPCR Evolution Database

GPCRs make up the largest family of human membrane proteins and of drug targets. Decades of experimental and structural work have revealed how these receptors operate at the molecular level, but this work has covered only a fraction of the superfamily, leaving the majority of receptors underexplored. To address this problem, we developed the GPCR Evolution Database, gpcrevolution.org, an open-access resource that makes high-quality evolutionary analysis of GPCRs available to every laboratory. Through our database, each human receptor can be examined against its own orthologs, where per-residue conservation reveals the sites that evolution has protected throughout that receptor's history. These orthologous lineages can then be compared with their paralogs within the same GPCR family, to distinguish residues shared across paralogous lineages, which likely support ancestral functions, from the lineage-specific residues that underlie functional differentiation between receptor subtypes. The database provides ortholog sets, multiple sequence alignments, phylogenetic trees and per-residue conservation scores for over 800 human GPCRs. The resource presents these through interactive conservation plots, sequence logos and snake plots, and provides tools for comparing conservation across two or more paralogous lineages. Overall, the GPCR Evolution Database provides the data and tools for researchers to examine GPCR function through an evolutionary lens, allowing molecular insights from well-studied receptors to be extended to their underexplored relatives.

bioinformatics↗

bioRxiv2026

The last bacterial common ancestor encoded a complex flagellum

Bacterial flagella are rotary nanomachines that enable motility in diverse environments. Although more than 40 genes are required to assemble, operate, and regulate a functional flagellum in model organisms, only 24 flagellar genes have previously been inferred to be conserved across bacteria. This discrepancy raises a fundamental question: did the last bacterial common ancestor encode a simpler, partial flagellum that was elaborated later in a lineage-specific manner, or does the apparent absence of conserved components reflect limitations in detecting highly diverged homologs? Here we combine large-scale profile- and sequence-based searches across a comprehensive bacterial genome set with conserved sequence signatures, gene-tree clustering and flagellar gene-neighborhood evidence to reconstruct the ancestral complexity of bacterial flagellar systems. We identify 28 additional flagellar gene families whose distributions and evolutionary histories support an origin before major bacterial diversification, yielding a 52-gene ancestral flagellum. The ancestral flagellum included all proteins of the secretion/export apparatus, basal body, axial components, motor-force generators and regulatory checkpoints required to build and operate a functional, contemporary flagellum. These findings revise models of early bacterial evolution and overturn the notion that the ancestral flagellum was genetically minimal. Instead, they suggest that the last bacterial common ancestor possessed a highly complex flagellar system comprising more components than are typically found in extant bacteria, many of whose flagella appear to have been shaped by lineage-specific gene loss.

microbiology↗

bioRxiv2022

Downregulated NPAS4 in multiple brain regions is associated with Major Depressive Disorder

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.

genetics↗

bioRxiv2021

Receptor-wide Determinants of G Protein Coupling Selectivity in Aminergic GPCRs

G protein-coupled receptors (GPCRs) induce signal transduction pathways through coupling to four main subtypes of G proteins (Gs, Gi, Gq, G12/13), selectively. However, G protein selective activation mechanisms and residual determinants in GPCRs have remained obscure. Herein, we performed an extensive phylogenetic analysis and identified specifically conserved residues for the receptors having similar coupling profiles in each aminergic receptor. By integrating our methodology of differential evolutionary conservation of G protein-specific amino acids with structural analyses, we identified selective 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 associated it with the larger TM6 tilt which is a signature of Gs-coupled receptors. Through molecular dynamics simulations, we showed that previously uncharacterized Glycine at position 7x41 plays an important role in both receptor activation and Gs coupling selectivity by inducing 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.

evolutionary biology↗

bioRxiv2020

Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey

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 thirty 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 two of the seventeen sub-clusters 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.

genomics↗