Biology subjects

Bankevich, A.

Publications and source records attributed to Bankevich, A..

7 recordsLinked to original sources

bioRxiv2026

Gene conversion facilitates rapid evolution of inversions across avian immunoglobulin loci

The genomic architecture of immunoglobulin (IG) loci in birds has received remarkably little attention, despite their relevance to infectious disease susceptibility. One of the few exceptions is the domestic chicken, which has been found to use a completely different mechanism to generate a diverse IG repertoire than most vertebrates; rather than relying on V(D)J recombination, chickens primarily use somatic gene conversion. Whether this is true of all birds has remained unknown and untestable at scale until now. And importantly, it is not known how this alternative mechanism for antibody generation shapes, and is shaped by, genome evolution in birds. Leveraging IG locus annotations from 122 bird species generated through the Vertebrate Genomes Project and 17 species from the California Conservation Genomics Project, we show that avian IGH loci display a striking, previously unreported architecture of recurrent inverted duplications that generate direct and inverted copies of the same repeat unit, found in no other vertebrate lineage. Inversion density varies considerably across species, and population-level analyses reveal that these inversions evolve rapidly. We propose a model in which these inversions are actively maintained because they continuously replenish a pool of highly similar pseudogenes that serve as donors for somatic gene conversion, substituting for the large functional V gene repertoires other vertebrates use to generate IG diversity. This model makes a direct prediction: IGH loci should harbor few functional genes and many pseudogenes, while IGL loci, which typically lack this inversion architecture, should show the opposite pattern. Our cross-species analysis confirms this. To test the model at the level of the expressed repertoire, we generated paired whole-genome and Iso-seq data from a single wild-caught Red-winged Blackbird. Consistent with our predictions, a single terminal IGLV gene is diversified through gene conversion from surrounding pseudogenes, while IGH carries a large donor pool at which we also detect gene conversion. Together, these findings reveal that the molecular evolution of IG in birds is governed by fundamentally different constraints and processes than in the rest of known vertebrates.

evolutionary biology↗

bioRxiv2026

Disruption of a CCR5-like immunoglobulin gene is linked to plague susceptibility in black-footed ferrets

Black-footed ferrets (Mustela nigripes) are among the worlds most endangered mammals and remain highly vulnerable to sylvatic plague caused by Yersinia pestis, yet the genetic basis of this susceptibility has remained unknown. Current conservation strategies rely on vaccination of captive-bred animals and large-scale flea control with insecticides, approaches that are costly, labor-intensive, and difficult to implement across the species natural range. Several closely related mustelid species, including the domestic ferret, are substantially more resistant to plague, providing an opportunity to identify naturally evolved immune mechanisms through comparative immunogenomics. Here we identify a conserved class of immunoglobulin lambda variable genes encoding unusually long antigen-binding loops with CCR5-mimicking sequence features that are widespread among Caniformia species. Because CCR5 has been implicated in host interactions with Yersinia species, we hypothesized that antibodies encoded by these germline genes contribute to plague resistance through receptor-like molecular mimicry. Consistent with this hypothesis, we show that these genes are under strong purifying selection in mustelids, are actively expressed in antibody repertoires, and monoclonal antibodies encoded by them reduced intracellular Y. pestis survival in macrophages. In contrast, all analyzed black-footed ferrets carried a frameshifting deletion resulting in loss of gene expression. These findings identify a naturally disrupted germline antibody gene as a candidate determinant of plague susceptibility in black-footed ferrets, demonstrating that variation in germline immunoglobulin genes can influence susceptibility to a lethal infectious disease. Ultimately, these findings lay the groundwork for genetically informed conservation management and the development of new antibody-based anti-plague strategies. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/734856v2_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@19d8ac1org.highwire.dtl.DTLVardef@a37aorg.highwire.dtl.DTLVardef@1ecd1e0org.highwire.dtl.DTLVardef@c6fd67_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

GnnDebugger: GNN based error correction in De Bruijn Graphs

MotivationModern sequencing technologies have enabled the reconstruction of complete mammalian genomes from telomere to telomere. However, scaling this achievement to thousands of species and population-level studies remains a challenge. Key bottlenecks include the low quality of the draft assemblies and the high coverage requirements. In particular, reconstructing complete and accurate sequences of both haplotypes in diploid genomes is especially difficult since the sequencing depth is not always sufficient to properly reconstruct diverged regions. Inspired by the success of neural networks in extracting patterns from the data on a massive scale, we introduce a method for correcting errors in De Bruijn Graphs using Graph Neural Networks. ResultsOur model provides a reliable classification of edges into correct and erroneous, especially for diploid genomes with coverage depth 35 and lower. We demonstrate that these predictions can guide the downstream read error correction algorithm and genome assembly, ultimately allowing for more accurate genome assembly. Availability and implementationBoth GnnDebugger (https://github.com/m5imunovic/gnndebugger) and LJA (https://github.com/AntonBankevich/LJA/tree/gnndebugger) are available on GitHub. Datasets used for training and testing of ML model are available at Zenodo: https://doi.org/10.5281/zenodo.15073168. HG002 reference and reads are available at https://github.com/marbl/HG002. Primates references and reads are available at https://github.com/marbl/Primates.

bioinformatics↗

bioRxiv2024

Complete sequencing of ape genomes

We present haplotype-resolved reference genomes and comparative analyses of six ape species, namely: chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan, and siamang. We achieve chromosome-level contiguity with unparalleled sequence accuracy (<1 error in 500,000 base pairs), completely sequencing 215 gapless chromosomes telomere-to-telomere. We resolve challenging regions, such as the major histocompatibility complex and immunoglobulin loci, providing more in-depth evolutionary insights. Comparative analyses, including human, allow us to investigate the evolution and diversity of regions previously uncharacterized or incompletely studied without bias from mapping to the human reference. This includes newly minted gene families within lineage-specific segmental duplications, centromeric DNA, acrocentric chromosomes, and subterminal heterochromatin. This resource should serve as a definitive baseline for all future evolutionary studies of humans and our closest living ape relatives.

genomics↗

bioRxiv2024

Unveiling Assembly Errors in Immunoglobulin Loci: A Comprehensive Evaluation of Long-read Genome Assemblies Across Vertebrates

Long-read sequencing technologies have revolutionized genome assembly producing near-complete chromosome assemblies for numerous organisms, which are invaluable to research in many fields. However, regions with complex repetitive structure continue to represent a challenge for genome assembly algorithms, particularly in areas with high heterozygosity. Robust and comprehensive solutions for the assessment of assembly accuracy and completeness in these regions do not exist. In this study we focus on the assembly of biomedically important antibody-encoding immunoglobulin (IG) loci, which are characterized by complex duplications and repeat structures. High-quality full-length assemblies for these loci are critical for resolving haplotype-level annotations of IG genes, without which, functional and evolutionary studies of antibody immunity across vertebrates are not tractable. To address these challenges, we developed a pipeline, "CloseRead", that generates multiple assembly verification metrics for analysis and visualization. These metrics expand upon those of existing quality assessment tools and specifically target complex and highly heterozygous regions. Using CloseRead, we systematically assessed the accuracy and completeness of IG loci in publicly available assemblies of 74 vertebrate species, identifying problematic regions. We also demonstrated that inspecting assembly graphs for problematic regions can both identify the root cause of assembly errors and illuminate solutions for improving erroneous assemblies. For a subset of species, we were able to correct assembly errors through targeted reassembly. Together, our analysis demonstrated the utility of assembly assessment in improving the completeness and accuracy of IG loci across species.

genomics↗

bioRxiv2020

Assembling Long Accurate Reads Using de Bruijn Graphs

Although most existing genome assemblers are based on the de Bruijn graphs, it remains unclear how to construct these graphs for large genomes and large k-mer sizes. This algorithmic challenge has become particularly important with the emergence of long high-fidelity (HiFi) reads that were recently utilized to generate a semi-manual telomere-to-telomere assembly of the human genome and to get a glimpse into biomedically important regions that evaded all previous attempts to sequence them. To enable automated assemblies of long and accurate reads, we developed a fast LJA algorithm that reduces the error rate in these reads by three orders of magnitude (making them nearly error-free) and constructs the de Bruijn graph for large genomes and large k-mer sizes. Since the de Bruijn graph constructed for a fixed k-mer size is typically either too tangled or too fragmented, LJA uses a new concept of a multiplex de Bruijn graph with varying k-mer sizes. We demonstrate that LJA improves on the state-of-the-art assemblers with respect to both accuracy and contiguity and enables automated telomere-to-telomere assemblies of entire human chromosomes.

bioinformatics↗

bioRxiv2020

mosaicFlye: Resolving long mosaic repeats using long error-prone reads

Long-read technologies revolutionized genome assembly and enabled resolution of bridged repeats (i.e., repeats that are spanned by some reads) in various genomes. However, the problem of resolving unbridged repeats (such as long segmental duplications in the human genome) remains largely unsolved, making it a major obstacle towards achieving the goal of complete genome assemblies. Moreover, the challenge of resolving unbridged repeats is not limited to eukaryotic genomes but also impairs assemblies of bacterial genomes and metagenomes. We describe the mosaicFlye algorithm for resolving complex unbridged repeats based on differences between various repeat copies and show how it improves assemblies of the human genome as well as bacterial genomes and metagenomes. In particular, we show that mosaicFlye results in a complete assembly of both arms of the human chromosome 6.

bioinformatics↗