Biology subjects

Yildirim, B.

Publications and source records attributed to Yildirim, B..

7 recordsLinked to original sources

bioRxiv2026

GLproxScape reconstructs spatial chromatin occupancy landscapes from tiled genomic locus proteomics

Genomic locus proteomics combines proximity labeling with mass spectrometry to identify the proteins associated with user-defined genomic loci. However, per-region enrichment values from tiled guide designs are typically pooled before hit calling, collapsing the latent spatial structure encoded by overlapping measurements. Here, we describe GLproxScape, an R package that treats per-region enrichments as indirect spatial measurements and reconstructs latent chromatin occupancy landscapes through a Gaussian labeling-kernel forward model. Sequence-specific transcription factors are resolved by motif-anchored non-negative least-squares deconvolution against JASPAR or HOCOMOCO position weight matrices, while chromatin regulators which lack defined DNA-binding motifs are inferred as broad occupancy zones, enabling recovery of overlapping members of multi-subunit complexes. Applied to published genomic locus proteomics datasets at the human TERT, MYC, FOXP2, and FOXQ1 loci and the mouse Ripk3 locus, GLproxScape recovered known regulators with predicted positions independently supported by ChIP-Atlas peaks, reconstructed candidate co-binding relationships, and identified chromatin complexes inaccessible to pooled analyses. Systematic sgRNA-ablation experiments further showed that densely tiled designs improve event recovery and positional stability, providing concrete experimental guidance for future genomic locus proteomics studies.

bioinformatics↗

bioRxiv2026

Gene-level complexity explains genome-wide variation in the distribution of fitness effects

The distribution of fitness effects (DFE) -- describing how harmful, neutral, or beneficial new mutations are -- is central to understanding how populations evolve. Although the DFE varies across genomes and species, it remains unclear which aspects of genomic organization drive this variation. Here, we inferred gene-level selective constraints across the genomes of Mus musculus castaneus, Drosophila melanogaster and Saccharomyces cerevisiae using a combination of population genetics and machine learning trained on diverse gene features. Many gene features were predictive of selective constraint, with conservation, gene structure, and expression being the most informative. These selective constraints delineated gene classes with distinct DFEs. Genes with higher connectivity and expression -- features reflecting how many traits a gene influences -- experienced stronger and less dispersed deleterious effects with increasing selective constraint. Between species, the rate of adaptation decreased with increasing organismal complexity, whereas across the genome it did not decrease monotonically with selective constraint, but tended to be higher at intermediate levels. While between-species comparisons of DFE parameters were less consistent with predictions of Fishers geometric model (FGM) based on organismal complexity, variation in DFE parameters across the genome aligned more closely with FGM when complexity was considered at the gene level. Our results suggest that gene-level complexity, captured by genomic feature proxies, provides a more informative definition of complexity for DFE variation than organism-level labels, and highlight the value of using gene features collectively to link genomic architecture, fitness landscapes, and patterns of molecular evolution.

evolutionary biology↗

bioRxiv2026

When South meets North: a joint contact zone coinciding with environmental gradients in three boreal tree species

Post-glacial recolonization of Fennoscandia created secondary contact zones in many species, offering opportunities to study how gene flow and selection contribute to their establishment and maintenance. Here, we analyse genomic data from three boreal tree species--Picea abies, Betula pendula, and Pinus sylvestris--sampled along a latitudinal gradient in Sweden. Despite differences in colonization timing and dispersal ecology, all three species exhibit north-south genetic structuring aligned with environmental gradients. Most notably, the two main genetic clusters within each species overlap in a shared contact zone, corresponding to the climatic transition between Swedens two major environmental zones. The extent and structure of the contact zone differ among species: P. abies shows stronger genetic structure and moderate gene flow, B. pendula exhibits intermediate differentiation and gene flow, and P. sylvestris displays the weakest structure with stronger gene flow. All three species also show genomic signatures of local adaptation, with distinct underlying architectures. In P. abies, adaptive loci are broadly distributed across the genome, while, strikingly, they are mostly found within an inversion on chromosome 1 in B. pendula. In P. sylvestris, local adaptation likely relies on subtle allele frequency shifts across many loci with weak signals. These patterns align with theoretical expectations for polygenic local adaptation under varying migration regimes. Our comparative approach demonstrates how gene flow and selection jointly shape genomic landscapes in shared environments and contributes to understanding local adaptation in forest trees, with implications for predicting species responses to climate change.

evolutionary biology↗

bioRxiv2024

Temporal Microbiome Changes in Axolotl Limb Regeneration: Stage-Specific Restructuring of Bacterial and Fungal Communities with a Flavobacterium Bloom During Blastema Proliferation

The intricate relationship between regeneration and microbiota has recently gained attention, spanning diverse model organisms. Axolotl (Ambystoma mexicanum) is a critically endangered salamander species and a model organism for regenerative and developmental biology. Despite its significance, a noticeable gap exists in understanding the interplay between axolotl regeneration and its microbiome. Here, we analyze in depth bacterial 16S rRNA amplicon dataset that we reported before as data resource and profile fungal community by sequencing ITS amplicons at the critical stages of limb regeneration (0-1-4-7-30-60 days post amputation, "dpa"). Results reveal a decline in richness and evenness in the course of limb regeneration, with bacterial community richness recovering beyond 30 dpa unlike fungi community. Beta diversity analysis reveals precise restructuring of the bacterial community along the three phases of limb regeneration, contrasting with less congruent changes in the fungal community. Temporal dynamics of the bacterial community highlight prevalent anaerobic bacteria in initiation phase and Flavobacterium bloom in the early phase correlating with limb blastema proliferation. Predicted functional analysis mirrors these shifts, emphasizing a transition from amino acid metabolism to lipid metabolism control. Fungal communities shift from Blastomycota to Ascomycota dominance in the late regeneration stage. Our findings provide ecologically relevant insights into stage specific role of microbiome contributions to axolotl limb regeneration.

microbiology↗

bioRxiv2023

Inference of Genomic Landscapes using Ordered Hidden Markov Models with Emission Densities (oHMMed)

BackgroundGenomes are inherently inhomogeneous, with features such as base composition, recombination, gene density, and gene expression varying along chromosomes. Evolutionary, biological, and biomedical analyses aim to quantify this variation, account for it during inference procedures, and ultimately determine the causal processes behind it. Since sequential observations along chromosomes are not independent, it is unsurprising that autocorrelation patterns have been observed e.g., in human base composition. In this article, we develop a class of Hidden Markov Models (HMMs) called oHMMed (ordered HMM with emission densities, the corresponding R package of the same name is available on CRAN): They identify the number of comparably homogeneous regions within autocorrelated observed sequences. These are modelled as discrete hidden states; the observed data points are realisations of continuous probability distributions with state-specific means that enable ordering of these distributions. The observed sequence is labelled according to the hidden states, permitting only neighbouring states that are also neighbours within the ordering of their associated distributions. The parameters that characterise these state-specific distributions are inferred. ResultsWe apply our oHMMed algorithms to the proportion of G and C bases (modelled as a mixture of normal distributions) and the number of genes (modelled as a mixture of poisson-gamma distributions) in windows along the human, mouse, and fruit fly genomes. This results in a partitioning of the genomes into regions by statistically distinguishable averages of these features, and in a characterisation of their continuous patterns of variation. In regard to the genomic G and C proportion, this latter result distinguishes oHMMed from segmentation algorithms based in isochore or compositional domain theory. We further use oHMMed to conduct a detailed analysis of variation of chromatin accessibility (ATAC-seq) and epigenetic markers H3K27ac and H3K27me3 (modelled as a mixture of poisson-gamma distributions) along the human chromosome 1 and their correlations. ConclusionsOur algorithms provide a biologically assumption-free approach to characterising genomic landscapes shaped by continuous, autocorrelated patterns of variation. Despite this, the resulting genome segmentation enables extraction of compositionally distinct regions for further downstream analyses.

bioinformatics↗

bioRxiv2023

Neutral sequence evolution in short introns of Drosophila melanogaster

Population genetic inference of selection on the nucleotide sequence level often proceeds by comparison to a reference sequence evolving only under mutation and population demography. Among the few candidates for such a reference sequence is the 5 part of short introns (5SI) in Drosophila. In addition to mutation and population demography, however, there is evidence for a weak force favoring GC bases, likely due to GC-biased gene conversion (gBGC), and for the effect of linked selection. Here, we use polymorphism and divergence data of Drosophila melanogaster to detect and describe the forces affecting the evolution of the 5SI. We separately analyze mutation classes, compare them between chromosomes, and relate them to recombination rate frequencies. GC-conservative mutations seem to be mainly influenced by mutation and drift, with linked selection mostly causing differences between the central and the peripheral (i.e., telomeric and centromeric) regions of the chromosome arms. Comparing GC-conservative mutation patterns between autosomes and the X chromosome, showed differences in mutation rates, rather than linked selection, in the central chromosomal regions after accounting for differences in effective populations sizes. On the other hand, GC-changing mutations show asymmetric site frequency spectra, indicating the presence of gBGC, varying among mutation classes and in intensity along chromosomes, but approximately equal in strength in autosomes and the X chromosome.

evolutionary biology↗

bioRxiv2022

Avoidance of premature splicing in short introns explains the polypyrimidine tract

Among eukaryotes, the major spliceosomal pathway is highly conserved. While long introns may contain additional regulatory sequences, the ones in short introns seem to be nearly exclusively related to splicing. Although these regulatory sequences involved in splicing are well-characterized, little is known about their evolution. At the 3 end of introns, the splice signal nearly universally contains the dimer AG, which consists of purines, and the polypyrimidine tract upstream of this 3 splice signal is characterized by over-representation of pyrimidines. If the over-representation of pyrimidines in the polypyrimidine tract is also due to avoidance of a premature splicing signal, we hypothesize that AG should be the most under-represented dimer. Through the use of DNA-strand asymmetry patterns, we confirm this prediction in fruit flies of the genus Drosophila and by comparing the asymmetry patterns to a presumably neutrally evolving region, we quantify the selection strength acting on each motif. Moreover, our inference and simulation method revealed that the best explanation for the base composition evolution of the polypyrimidine tract is the joint action of purifying selection against a spurious 3 splice signal and the selection for pyrimidines . Patterns of asymmetry in other eukaryotes indicate that avoidance of premature splicing similarly affects the nucleotide composition in their polypyrimidine tracts.

evolutionary biology↗