Biology subjects

Igolkina, A. A.

Publications and source records attributed to Igolkina, A. A..

7 recordsLinked to original sources

bioRxiv2025

Pannagram: unbiased pangenome alignment and the Mobilome calling

Pangenomes capture genetic variation beyond the scope of single-reference analyses, but interpreting this variation requires approaches that translate whole-genome comparisons into biologically meaningful features. We present Pannagram, a framework combining reference-free linear whole-genome alignment with feature extraction for single-nucleotide polymorphisms (SNPs), structural variants (SVs), and mobile element families (MEFs), together with a library of tools for downstream analysis. Pannagram identifies MEFs by a single criterion, recent mobility, independent of prior transposable element (TE) models or homology. Illustrating its utility through a meta-analysis of pangenome data from 60 insect species, we show that highly similar MEFs, by definition recently active, are frequently shared between species, providing strong evidence for horizontal transfer (HT) orthogonal to sequence similarity and phylogeny. We further find that vectors for such HT include not only viruses but also polintons, supported by cases of polinton HT and by polintons that remain active after insertion of TE cargo.

bioinformatics↗

bioRxiv2022

Case-control analysis of single-cell RNA-seq studies

Single-cell RNA-seq (scRNA-seq) assays are being increasingly utilized to investigate specific hypotheses in both basic biology and clinically-applied studies. The design of most such studies can be often reduced to a comparison between two or more groups of samples, such as disease cases and healthy controls, or treatment and placebo. Comparative analysis between groups of scRNA-seq samples brings additional statistical considerations, and currently there is a lack of tools to address this common scenario. Based on our experience with comparative designs, here we present a computational suite (Cacoa - case-control analysis) to carry out statistical tests, exploration, and visualization of scRNA-seq sample cohorts. Using multiple example datasets, we demonstrate how application of these techniques can provide additional insights, and avoid issues stemming from inter-individual variability, limited sample size, and high dimensionality of the data.

bioinformatics↗

bioRxiv2021

Heterogeneity of the GFP fitness landscape and data-driven protein design

Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Counterintuitively, mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design - instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering.

synthetic biology↗

bioRxiv2021

The role of AUX1 during lateral root development in the domestication of the model C4 grass Setaria italica

C4 photosynthesis increases the efficiency of carbon fixation by spatially separating high concentrations of molecular oxygen from rubisco. The specialized leaf anatomy required for this separation evolved independently many times. C4 root systems are highly branched, an adaptation thought to support high rates of photosynthesis; however, little is known about the molecular mechanisms that have driven the evolution of C4 root system architecture (RSA). Using a mutant screen in the C4 model plant Setaria italica, we identify siaux1-1 and siaux1-2 as RSA mutants, and use CRISPR/cas9-mediated genome editing and overexpression to confirm the importance of the locus. As AUX1 is not necessary for lateral root emergence in S. viridis, the species from which S. italica was domesticated, we conducted an analysis of auxin responsive elements in the promoters of auxin-responsive gene families in S. italica, and explore the molecular basis of SiAUX1s role in seedling development using an RNAseq analysis of wild type and siaux1-1 plants. Finally, we use a root coordinate system to compare cell-by-cell meristem structures in siaux1-1 and wild type Setaria plants, observing changes in the distribution of cell volumes in all cell layers and a dependence in the frequency of protophloem and protoxylem strands on siAUX1.

plant biology↗

bioRxiv2021

Historical trade routes for diversification of domesticated chickpea inferred from landrace genomics

According to archaeological records, chickpea (Cicer arietinum) was first domesticated in the Fertile Crescent 10 thousand years ago. Its subsequent diversification in South Asia, Ethiopia, and the Western Mediterranean, however, remains obscure and cannot be resolved using only archeological and historical evidence. In particular, chickpea has two market types: desi, which has a similar flower and seed coat color to chickpeas wild relatives; and kabuli, which has light-colored seed, and is linguistically tied to Central Asia but has an unknown geographic origin. Based on the genetic data from 421 chickpea landraces from six geographic regions, we tested complex historical hypotheses of chickpea migration and admixture on two levels: within and between major regions of cultivation. For the former, we developed popdisp, a Bayesian model of population dispersal from a regional center towards sample locations, and confirmed that chickpea spread within each region along trade routes rather than by simple diffusion. For the latter, migration between regions, we developed another model, migadmi, that evaluates multiple and nested admixture events. Applying this model to desi populations, we found both Indian and Middle Eastern traces in Ethiopian chickpea, suggesting presence of a seaway from South Asia to Ethiopia -- and the cultural legacy of the Queen of Sheba. As for the origin of kabuli chickpeas, we found significant evidence for an origin from Turkey rather than Central Asia.

plant biology↗

bioRxiv2020

Towards understanding Afghanistan pea symbiotic phenotype through the molecular modeling of the interaction between LykX-Sym10 receptor heterodimer and Nod factors

The difference in symbiotic specificity between peas of Afghanistan and European phenotypes was interrogated using molecular modeling. Considering segregating amino acid polymorphism, we examined interactions of pea LykX-Sym10 receptor heterodimers with four forms of Nod factor (NF) that varied in natural decorations (acetylation and length of the glucosamine chain). First, we showed the stability of the LykX-Sym10 dimer during molecular dynamics (MD) in solvent and in the presence of a membrane. Then, four NFs were separately docked to one European and two Afghanistan dimers, and the results of these interactions were in line with corresponding pea symbiotic phenotypes. The European variant of the LykX-Sym10 dimer effectively interacts with both acetylated and non-acetylated forms of NF, while the Afghanistan variants successfully interact with the acetylated form only. We additionally demonstrated that the length of the NF glucosamine chain contributes to controlling the effectiveness of the symbiotic interaction. The obtained results support a recent hypothesis that the LykX gene is a suitable candidate for the unidentified Sym2 allele, the determinant of pea specificity towards Rhizobium leguminosarum bv. viciae strains producing NFs with or without an acetylation decoration. The developed modeling methodology demonstrated its power in multiple searches for genetic determinants, when experimental detection of such determinants has proven extremely difficult.

plant biology↗

bioRxiv2018

The Evolutionary Moulding in plant-microbial symbiosis: matching population diversity of rhizobial nodA and legume NFR5 genes

We propose the Evolutionary Moulding hypothesis that population diversities of partners in nitrogen-fixing rhizobium-legume symbiosis are matched, and tested it in nucleotide polymorphism of symbiotic genes encoding two components of the plant-bacteria signalling system. The first component is the rhizobial nodA acyltransferase involved in the fatty acid tail decoration of Nod factor (rhizobia signalling molecule). The second component is the plant NFR5 receptor, putatively required for Nod-factor binding.\n\nWe collected three wild growing legume species together with soil samples adjacent to the roots (soil pool) from one large 25-year fallow: Vicia sativa, Lathyrus pratensis and Trifolium hybridum nodulated by one of the two Rhizobium leguminosarum biovars (viciae and trifolii). For each plant species we prepared three pools for DNA extraction: the plant pool (30 plant indiv.), the nodule pool (90 nodules) and the soil pool (30 samples). NFR5 gene libraries from the plant pool and nodA gene libraries from nodule and soil pools were sequenced by Sanger technology and High-throughput pyrosequencing, respectively. Analysis of the data demonstrated concordance in population diversities of one symbiotic partner (rhizobia) the second partner (legume host), in line with the Evolutionary Moulding hypothesis. This effect was evinced by the following observations for each plant species: (1) significantly increased diversity in the nodule nodA popset (set of gene sequences derived from the nodule population) compared to the soil popset; (2) a monotonic relationship between the diversity in the plant NFR5 gene popset and the nodule rhizobial nodA gene popset; and (3) higher topological similarity of the NFR5 gene tree with the nodA gene tree of the nodule popset, than with the nodA gene tree of the soil popset. Both nonsynonymous diversity and Tajimas D were increased in the nodule popsets compared to the soil popsets, consistent with relaxation of negative selection and/or admixture of balancing selection underlying the Evolutionary Moulding effect. We propose that the observed genetic concordance arises from the selection of particular characteristics of the nodule nodA genes by the host plant.

evolutionary biology↗