Biology subjects

Durbin, R.

Publications and source records attributed to Durbin, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Efficient and precise discovery of LTR-retrotransposon families using HiRepEat

Long Terminal Repeat Retrotransposons (LTR-RTs) are mobile genetic elements that replicate within host genomes using an RNA intermediate. Recent high quality genome assemblies provide new opportunities to study these repetitive elements across evolutionary timescales. We adapt the Myers O(Nd) wavefront alignment algorithm to produce a new fast LTR detection, clustering and phylogenetically-informed consensus approach for identifying LTR-RT families in new genome sequences. We present an iterative approach to identifying and removing repeats, initially tandem repeats, that we call TACO (TAndem COmpressor), and a corresponding coordinate mapping system we call SALSA (Sorted Array for Liftover of Sequence Addresses). Together these allow us to read and write in reduced genome space and search for LTR-RTs and tandem repeats in a series of operations. This greatly reduces confounding between different repeat types and allows us to uncover nested insertions. We show results from our clustering and consensus approach across the >500 genomes in the Vertebrate Genomes Project, with analysis completing in most cases in under 60 minutes with 15Gb memory and 16 cores. We also present cross-genome LTR-RT clustering across 30 Drosophila species, as well as across the VGP, providing fine-grained resolution on species-sharing patterns of LTR-RTs and revealing candidates for horizontal transfer.

bioinformatics↗

bioRxiv2026

An atlas of eukaryotic centromere architecture reveals recurrent evolutionary dynamics

Centromeres evolved at the root of eukaryotes to segregate chromosomes during cell division. Despite their ancient origin, centromeric DNA sequences evolve rapidly and adopt diverse architectures, including point centromeres, satellite arrays, transposon clusters, and holocentrics. To analyse centromere evolution at a broad scale, we characterised architectures across 325 diverse Darwin Tree of Life genome assemblies. Centromere architecture is evolutionarily labile, and similar configurations arise independently across divergent lineages. In plants and animals, we modelled centromere evolution as a recurrent cycle, in which satellite- and transposon-based architectures interconvert, with independent origins of holocentricity. We curated >23 million satellite repeats comprising 263 families from 165 species. Despite sequence divergence between satellite families, higher order repeats are prevalent, indicating constraint on repeat architecture rather than primary sequence. Satellite arrays are heavily invaded by diverse transposon families, consistent with convergent adaptation to the centromeric niche. In 89 species, transposons themselves constitute the primary centromere structure. We observed centrophilic transposons forming tandem arrays, suggesting mechanisms for satellite regeneration. Our sample includes five independent origins of holocentricity in plants and animals, which vary in association with periodic satellite arrays. We propose that genetic instability, centrophilic transposition, and transmission distortion promote recurrent centromere architectural interconversions during evolution.

genomics↗

bioRxiv2026

The relationship of genetic diversity and inbreeding to extinction risk across over 500 vertebrate diploid genomes

Genetics may help address the biodiversity crisis by providing information about genetic diversity and temporal changes in demography for species of interest. Advances in whole-genome sequencing create new opportunities for demographic analysis, even based on the two copies of a genome found in a single diploid individual. The Vertebrate Genomes Project (VGP) is generating high-quality, chromosome-level reference genomes across the full range of extant vertebrate species, with its first phase delivering assemblies spanning approximately 95% of vertebrate orders. Using 512 diploid VGP genomes, we quantified intra-species heterozygosity, runs of homozygosity (ROH), and inferred past effective population sizes (Ne) with the Pairwise Sequentially Markovian Coalescent (PSMC). Threatened species are more likely to exhibit lower heterozygosity and longer ROH, though there is large variation in both measures across all IUCN categories. Interestingly, PSMC suggests that estimated historical Ne several thousand generations ago is a better predictor of threatened status than the present day estimate. Co-analysing with life history traits, we found that marine species tend to have lower ROH content, while fossorial species show significantly higher inbreeding levels. Indeed, habitat and foraging strata are much stronger predictors of IUCN status than genetics, with estimated historical Ne providing a small but significant amount of additional information. Together, these results suggest that, while measures of genetic diversity are correlated with IUCN status, much of that correlation may derive from ecological factors such as habitat, with only a relatively small direct contribution. Nevertheless, reference genomes like those generated by the VGP can yield valuable information, like historical Ne, while facilitating population monitoring and management for species of interest.

genomics↗

bioRxiv2026

Near-complete genomes for nine haplochromine cichlid fishes reveal a novel centromeric satellite structure organised around a pair of inverted elements

The haplochromine cichlid fishes of Lake Malawi form one of the most dramatic examples of recent rapid radiation in vertebrates. Here we describe nine new diploid telomere-to-telomere (T2T) genome sequences generated using ultra-long ONT reads, which include 78 ungapped chromosomes. We provide accurate annotations of transposable elements and tandem repeats, identify rDNA cluster regions and putative centromeres, and confirm previously reported large chromosomal inversions. The putative centromeres are primarily composed of satellite tandem arrays of previously reported 237 bp repeats, but notably on most chromosomes these are organised in a novel structure in which four blocks of satellites in alternating orientation are separated by an inverted pair of [~]15 kb sequences we term "centroids", which have similarity to a non-autonomous DNA transposable element and containing potential CENP-B binding boxes. The methylation dip region indicating the likely active centromere always lies between the centroids, whose separation is almost always around 200 kb (interquartile range 151-221kb). A structurally equivalent but non-homologous organisation is seen in the distantly related Etroplus cichlid genera from South Asia. By comparing these structures across chromosomes and species, we suggest how they may have evolved, and potentially how they could contribute to the rampant sympatric speciation seen in these species, based on meiotic drive and chromosome missegregation.

genomics↗

bioRxiv2026

340 dipteran genomes reveal the origin of Muller elements and sex chromosomes in Diptera

Diptera genome evolution is traditionally viewed through the lens of Drosophila melanogaster. To provide an unbiased picture of chromosome evolution in Diptera, we reconstructed six ancestral linkage groups (ALGs) and their rearrangements using 340 chromosome-level genome assemblies from 59 dipteran Families and two outgroups. Notably, Diptera ALGs are conserved in many Nematoceran lineages, while emergence of Brachycera coincided with four chromosomal fissions, which subsequently fused in various combinations. In Schizophora and relatives, a stable karyotype of five metacentric chromosomes and a chromosome homologous to the dot emerged that is remarkably stable with the notable exception of Drosophila, where the metacentric chromosomes became acrocentric Muller elements. Furthermore, our reconstruction reveals an ancient sex chromosome system associated with a small and gene-poor ALG that frequently fused to other chromosomes.

genomics↗

bioRxiv2026

A new phased assembly of the Antarctic spiny plunderfish provides novel insights into the evolution of the notothenioid radiation.

BackgroundNotothenioids are a well characterised species flock endemic to the Antarctic and an important model group for the study of genome adaptation to extreme cold. We used a new reference assembly and clade-wide comparative genomic analysis to investigate cryonotothenioid evolution and the appearance of novel functionalities linked to cold adaptation. ResultsA new phased assembly of a model notothenioid, Harpagifer antarcticus, demonstrated low levels of haplotypic variability across the genome. Nevertheless, numerous insertions from multiple LINE-L2 clades were found, suggesting ongoing transposition with potential contribution to speciation. Contrary to expectations the afgp locus was highly similar between haplotypes, except for large length allelic variants of afgp genes. Analysis suggests a model for the afgp locus expansion in H. antarcticus through segmental tandem duplications involving two pairs of afgp genes at time. Syntenic reconstruction of genomes from across the clade demonstrates conserved macrosyntenic relationships and group specific chromosomal fusions of notothenioids. Quantification of genome gain and transposition rates during cryonotothenioid diversification showed a first ancestral slow genome expansion concurrent with historic temperature drops. This was followed by lineage-specific massive peaks of genomic gain and transposition activity. Finally, we identified a set of genes that underwent ancestral diversifying selection and acquired novel conserved non-coding elements during the cryonotothenioid emergence. These were related to antioxidants and proteostasis, which may have facilitated the notothenioid Antarctic radiation. ConclusionDiversifying selection and genomic gain linked to transposon activity are primary contributors to lineage-specific evolutionary dynamics through the clade which facilitated adaptation to life in the cold.

genomics↗

bioRxiv2026

Genetic architecture of cichlid brain morphology

How evolutionary and developmental processes interact to determine axes of neural variation that produce behavioural diversity has been debated for many decades, with alternative hypotheses giving differential emphasis to functional coupling, which favours co-evolution, and developmental constraint, which enforces it. A critical omission is data on the genetic architecture of brain size and structure, which more closely illuminates the shared developmental dependencies between components of an integrated system. Here, we exploit ecological divergence between Astatotilapia calliptera and Aulonocara stuartgranti, two closely related cichlid species from Lake Malawi, to explore the genetic architecture of brain evolution. Using computer vision and machine learning techniques to extract volumetric data from micro-tomographic images, we first demonstrate significant divergence in brain composition between these species. Genomic and micro-tomographic imaging data from a population of hybrids generated between the two species were used to investigate genetic factors shaping this differentiation. We show that the majority of brain components are integrated phenotypically in hybrids, but genetic correlations between them are generally weaker. We further show that variation in multiple brain components is associated with variation in largely structure-specific quantitative trait loci, rather than determined by genetic factors with broad effects across the entire brain. These results suggest a genetic architecture that can facilitate modular changes in brain structure, and imply that individual components are independently evolvable.

evolutionary biology↗

bioRxiv2026

A run-length-compressed skiplist data structure for dynamic GBWTs supports time and space efficient pangenome operations over syncmers

Skiplists (Pugh, 1990) are probabilistic data structures over ordered lists supporting [O] (log N) insertion and search, which share many properties with balanced binary trees. Previously we introduced the graph Burrows-Wheeler transform (GBWT) to support efficient search over pangenome path sets, but current implementations are static and cumbersome to build and use. Here we introduce a doubly-linked skiplist variant over run-length-compressed BWTs that supports [O] (log N) rank and access operations, and a dynamic version of this that supports [O] (log N + S) rank and insert operations, where S is the number of symbols in the alphabet. We use these to store and search over paths through a syncmer graph built from Edgars closed syncmers, equivalent to a sparse de Bruijn graph. Code is available in rskip.[ch] within the syng package at github.com/richarddurbin/syng. This builds a 5.8 GB lossless GBWT representation of 92 full human genomes, single-threaded in 52 minutes, on top of a 4GB 63bp syncmer set built in 37 minutes. Arbitrarily long maximal exact matches (MEMs) can then be found as seeds for sequence matches to the graph at a search rate of approximately 1Gbp per 10 seconds per thread.

bioinformatics↗

bioRxiv2026

Phylogenomics of Cypriniformes, the most diverse order of freshwater fishes: consensus, challenges and limitations

Cypriniformes, the most species-rich order of freshwater fishes ([~]5,000 species), represents a key lineage for understanding vertebrate diversification in freshwater ecosystems. This clade includes several highly miniaturized and understudied lineages whose phylogenetic placements have long remained contentious. Here, we present the first phylogenomic analysis of Cypriniformes with complete family-level representation and broad genus-level coverage, encompassing 316 species comprising approximately 30% of all described genera. Our dataset integrates 257 newly assembled genomes with publicly available resources and analyzes multiple sets of genome-wide markers using both concatenation-based and coalescent-aware approaches. The general concordance among analytical frameworks indicates that the backbone topology of Cypriniformes is now established, allowing clear identification between well-supported clades and regions of persistent conflict. Our results strengthen the evolutionary relationships of several miniaturized lineages, while identifying recalcitrant relationships shaped by both biological processes and model artefacts that can yield superficially similar patterns of phylogenetic conflict. Our study substantially expands genomic representation and establishes a phylogenomic foundation for future comparative, developmental, and evolutionary research in this freshwater radiation.

evolutionary biology↗

bioRxiv2025

Somatic and germline mutational processes across the tree of life

The characterisation of mutational processes active in somatic and germline cells in vivo has predominantly focused on human cancers1,2, normal tissues3-5 and model organisms6-8. Beyond mammals9, little is known about mutational processes across the tree of life. We developed himut (high-fidelity mutation), an algorithm to identify somatic mutations from circular consensus long-read sequencing data, deploying it on 708 samples from 661 species from Britain and Ireland10. The spectra of somatic mutations, categorised by mutation type and local sequence context, showed considerable between-species divergence but within-species similarity. From normalised spectra across the dataset, we extracted 95 distinct patterns, or signatures, of somatic mutations, together with 18 signatures of germline mutational processes. Only two of the somatic signatures resembled mutational signatures extracted from human cancers1,2. Of the somatic signatures, 22 had significant clustering within the taxonomic classification, with some distributed across an entire kingdom or phylum, while others were restricted to a single family or species. Three somatic signatures were found only in water-dwelling species, with one distributed across multiple clades that might suggest it derives from a water-borne mutagen. Of germline signatures, eight were found in multiple species, showed significant clustering by taxonomic classification and had counterpart somatic signatures with matching mutational spectrum and species distribution. Thus, there is considerably greater diversity of mutational processes across the tree of life than found in human samples, likely reflecting either cell-intrinsic biological processes or environmental exposures (or both) operative within distinct clades.

genomics↗

bioRxiv2025

fgf8a signalling shapes brain divergence between Malawi cichlids

Brain diversification is intimately linked with adaptive radiations, yet the underlying molecular basis remains poorly understood. Here, we examine the mechanisms of neural evolution in two ecologically divergent Lake Malawi cichlid species: a generalist, Astatotilapia calliptera, and a pelagic piscivore, Rhamphochromis sp. chilingali. We demonstrate that forebrain domains diverged independently from other brain regions in these species, consistent with mosaic brain evolution. We identify fibroblast growth factor 8a (fgf8a) as a key factor underlying this neuroanatomical divergence. Species-specific fgf8a expression patterns during critical developmental windows correlate with adult brain differences. Functional knockout experiments confirm fgf8as essential role in cichlid brain patterning, directly linking this conserved developmental gene to interspecific neuroanatomical variation. We identify species-specific transposable element repertoires in the Malawi cichlid fgf8a locus that function as developmental enhancers in brain and sensory systems, providing a potential mechanism for expression divergence between species. Phylogenetic analysis across the radiation reveals elevated transposable element polymorphism at the fgf8a locus in Rhamphochromis, suggesting ongoing regulatory evolution in this clade. Our findings reveal how conserved developmental programmes can accommodate regulatory modification, providing a mechanistic framework for understanding rapid neural diversification during adaptive radiation.

developmental biology↗

bioRxiv2025

The genomics of convergent adaptation to intertidal gravel beaches in Mediterranean clingfishes

IntroductionUnderstanding the genetic basis of widespread phenotypic convergence, particularly for complex morphological traits, remains a major challenge in evolutionary biology. The Mediterranean gravel beach clingfishes of the genus Gouania provide an excellent system to study this phenomenon. Within this genus, two distinct morphotypes, "slender" and "stout", have repeatedly evolved, adapting to different microhabitats. These morphotypes differ in multiple complex traits, including body elongation, head compression, vertebral number, eye size, and the structure of the adhesive disc. Materials and MethodsIn a first step, to scrutinize phylogenetic convergence, we combined 3D morphometrics of the pelvic girdle and skull, with molecular species delimitation based on >660 DNA barcodes, and a phylogenomic framework based on more than 3,400 single-copy orthologs. Secondly, by employing whole-genome resequencing and a novel "convergence score" statistic, we examined genomic convergence across multiple levels: nucleotides, sequences, genes, and functional pathways. Results and DiscussionWhile we found no evidence of large-scale genomic or protein-level convergence, we identified promising candidate regions at the level of single variants, genes, and biological pathways. Notably, a longer shared (but interrupted) haplotype around the morphogene adam12 was associated with convergent traits. The lack of simple genomic patterns may reflect the radiations age and the complex genetic basis of the underlying morphological traits (e.g., eye-size, neurocranium shape). Altogether, our findings highlight the importance of assessing genomic convergence at multiple molecular levels to uncover diagnostic signals across varying evolutionary processes and timescales. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=149 SRC="FIGDIR/small/675783v1_ufig1.gif" ALT="Figure 1"> View larger version (61K): org.highwire.dtl.DTLVardef@58265eorg.highwire.dtl.DTLVardef@13f1deaorg.highwire.dtl.DTLVardef@c51d79org.highwire.dtl.DTLVardef@112217d_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2025

Pangenome-guided sequence assembly via binary optimisation

De novo genome assembly is challenging in highly repetitive regions; however, reference-guided assemblers often suffer from bias. We propose a framework for pangenome-guided sequence assembly, which can resolve short-read data in complex regions without bias towards a single reference genome. Our method frames assembly as a graph traversal optimisation problem, which can be implemented on quantum computers. The pipeline first annotates pangenome graphs with estimated copy numbers for each node, then finds a path on the graph that best explains those copy numbers. On simulated data, our approach significantly reduces the number of contigs compared to de novo assemblers. While it introduces a small increase in inaccuracies, such as false joins, our optimisation-based methods are competitive with current exhaustive search techniques. They are also designed to scale more efficiently as the problem size grows and will run effectively on future quantum computers.

genomics↗

bioRxiv2025

FastGA: Fast Genome Alignment

FastGA finds alignments between two genome sequences more than an order of magnitude faster than previous methods that have comparable sensitivity. Its speed is due to (a) a carefully engineered architecture involving only cache-coherent MSD radix sorts and merges, (b) a novel algorithm for finding adaptive seed hits in a linear merge of sorted k-mer tables, and (c) a variant of the Myers adaptive wave algorithm [1] to find alignments around a chain of seed hits that detects alignments with up to 25-30% variation. It further does not require pre-masking of repetitive sequence, and stores millions of alignments in a fraction of the space of a conventional CIGAR-string [2] using a trace-point encoding that is further compressed by the ONEcode data system [3] introduced here. As an example, two bat genomes of size 2.2Gbp and 2.5Gbp can be compared in a little over 2 minutes using 8 threads on an Apple M4 Max laptop using 5.7GB of memory and producing 1.05 million alignments totaling 1.63Gbp of aligned sequence that cover about 60% of each genome. The output "ALN"-formatted file occupies 66MB. This file can be converted to a PAF file with CIGAR strings in 6 seconds, where the PAF representation is a significantly larger 1.03GB file. FastGA is freely available at github: http://www.github.com/thegenemyers/FASTGA along with utilities for viewing inputs, intermediate files, and outputs and transforming outputs into other common formats. Specifically, FastGA can, in addition to its highly efficient ONEcode representation, output PSL-formatted alignments, or PAF-formatted alignments with or without CIGAR strings explicitly encoding the alignments. There is also a utility to chain FastGAs alignments and display them in a dot-plot like view in Postscript files, and an interactive viewer is in development.

bioinformatics↗

bioRxiv2025

Hi-reComb: constructing recombination maps from bulk gamete Hi-C sequencing

Recombination is central to genetics and to evolution of sexually reproducing organisms. However, obtaining accurate estimates of recombination rates, and of how they vary along chromosomes, continues to be challenging. To advance our ability to estimate recombination rates, we present Hi-reComb, a new method and software for estimation of recombination maps from bulk gamete chromosome conformation capture sequencing (Hi-C). Simulations show that Hi-reComb produces robust, accurate recombination landscapes. With empirical data from sperm of five fish species we show the advantages of this approach, including joint assessment of recombination maps and large structural variants, map comparisons using bootstrap, and workflows with trio phasing vs. Hi-C phasing. With off-the-shelf library construction and a straightforward rapid workflow, our approach will facilitate routine recombination landscape estimation for a broad range of studies and model organisms in genetics and evolutionary biology. Hi-reComb is open-source and freely available at https://github.com/millanek/Hi-reComb.

genetics↗

bioRxiv2024

Genomic diversity of the African malaria vector Anopheles funestus

Anopheles funestus s.s. is a formidable human malaria vector across sub-Saharan Africa. To understand how the species is evolving, especially in response to malaria vector control, we sequenced 656 modern specimens (collected 2014-2018) and 45 historic specimens (collected 1927-1967) from 16 African countries. We find high levels of genetic variation with clear and stable continental patterns. Six segregating inversions might be involved in adaptation of local ecotypes. Strong recent signals of selection centred on canonical insecticide resistance genes are shared by multiple populations. A promising gene drive target in An. gambiae is highly conserved in An. funestus. This work represents a significant advance in our understanding of the genetic diversity and population structure of An. funestus and will enable smarter targeted malaria control.

genomics↗

bioRxiv2024

Oatk: a de novo assembly tool for complex plant organelle genomes

Plant organelle genomes, particularly the large mitochondrial genomes with intricate repetitive structures, present significant challenges for assembly. The advent of long-read sequencing technologies provides a transformative opportunity to generate complete genomes, but problems of resolving alternative structures remain. Here we introduce a novel tool for plant organelle genome assembly from high-accuracy long reads. Our method employs a k-mer based assembler for rapid assembly graph construction, integrates a profile HMM gene database for robust organelle sequence annotation, and leverages a new search method to find the best supported path through the assembly graph. We describe high-quality organelle assemblies for 195 plant species and demonstrate improvements over other methods. The assembled genomes provide multiple insights into structural complexity, heteroplasmy, and DNA exchange between organelles.

bioinformatics↗

bioRxiv2024

Deep coalescent history of the hominin lineage

Coalescent-based methods are widely used to infer population size histories, but existing analyses have limited resolution at deep time scales (>2 million years ago). Here, using new high-quality telomere-to-telomere genome assemblies, we extend the scope of such inference and reanalyse an ancient peak in human effective population size around 3-6 million years ago, showing that coalescent-based inference can reach much further into the past than previously thought. Furthermore, peaks at approximately the same time as in humans are also observed in chimpanzee and bonobo, but not in gorilla or orangutans. We show that this pattern is unlikely to be an artefact of model violations and discuss its potential implications for understanding hominin evolutionary history. It is known that such peaks can arise from ancestral genetic structure, and consequently we suggest that a parsimonious explanation for the contemporaneous peaks in humans, chimpanzees and bonobos would be a period of complex speciation before final separation of Homo from Pan, in contrast to a scenario where these lineages diverge cleanly from a panmictic common ancestor.

genetics↗