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1. Genome-wide alignment-free phylogenetic distance estimation under a no strand-bias model

   https://doi.org/10.1093/bioadv/vbac055  

   Balaban, Metin; Bristy, Nishat Anjum; Faisal, Ahnaf; Bayzid, Md Shamsuzzoha; Mirarab, Siavash (January 2022, Bioinformatics Advances)

   Lengauer, Thomas (Ed.)

   Abstract   Summary: While alignment has been the dominant approach for determining homology prior to phylogenetic inference, alignment-free methods can simplify the analysis, especially when analyzing genome-wide data. Furthermore, alignment-free methods present the only option for emerging forms of data, such as genome skims, which do not permit assembly. Despite the appeal, alignment-free methods have not been competitive with alignment-based methods in terms of accuracy. One limitation of alignment-free methods is their reliance on simplified models of sequence evolution such as Jukes–Cantor. If we can estimate frequencies of base substitutions in an alignment-free setting, we can compute pairwise distances under more complex models. However, since the strand of DNA sequences is unknown for many forms of genome-wide data, which arguably present the best use case for alignment-free methods, the most complex models that one can use are the so-called no strand-bias models. We show how to calculate distances under a four-parameter no strand-bias model called TK4 without relying on alignments or assemblies. The main idea is to replace letters in the input sequences and recompute Jaccard indices between k-mer sets. However, on larger genomes, we also need to compute the number of k-mer mismatches after replacement due to random chance as opposed to homology. We show in simulation that alignment-free distances can be highly accurate when genomes evolve under the assumed models and study the accuracy on assembled and unassembled biological data. Availability and implementation Our software is available open source at https://github.com/nishatbristy007/NSB. Supplementary information Supplementary data are available at Bioinformatics Advances online. 

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2. wgatools : an ultrafast toolkit for manipulating whole-genome alignments

   https://doi.org/10.1093/bioinformatics/btaf132  

   Wei, Wenjie; Gui, Songtao; Yang, Jian; Garrison, Erik; Yan, Jianbing; Liu, Hai-Jun (March 2025, Bioinformatics)

   Alkan, Can (Ed.)

   Abstract SummaryWith the rapid development of long-read sequencing technologies, the era of individual complete genomes is approaching. We have developed wgatools, a cross-platform, ultrafast toolkit that supports a range of whole-genome alignment formats, offering practical tools for conversion, processing, evaluation, and visualization of alignments, thereby facilitating population-level genome analysis and advancing functional and evolutionary genomics. Availability and implementationwgatools supports diverse formats and can process, filter, and statistically evaluate alignments, perform alignment-based variant calling, and visualize alignments both locally and genome-wide. Built with Rust for efficiency and safe memory usage, it ensures fast performance and can handle large datasets consisting of hundreds of genomes. wgatools is published as free software under the MIT open-source license, and its source code is freely available at https://github.com/wjwei-handsome/wgatools and https://zenodo.org/records/14882797. 

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3. Distinct patterns of genome size evolution in each bryophyte lineage are not correlated with whole genome duplication

   https://doi.org/10.1093/aob/mcaf012  

   Patel, Nikisha; Budke, Jessica M; Bainard, Jillian D (January 2025, Annals of botany)

   Abstract Background and AimsGenome size varies by orders of magnitude across land plants, and the factors driving evolutionary increases and decreases in genome size vary across lineages. Bryophytes have the smallest genomes relative to other land plants, and there is growing evidence for frequent whole genome duplication (WGD) across the lineage. However, the broad patterns of genome size, chromosome number and WGD have yet to be characterized across bryophytes in a phylogenetic context. MethodsIn the present study, we adopt a phylogenetic comparative approach and leverage previously published data on genome size, chromosome number and WGD to reconstruct the evolutionary history of these traits across the three major bryophyte lineages: hornworts, liverworts and mosses. We infer ancestral haploid chromosome numbers for each lineage and introduce a novel metric for assessing polyploidy using chromosome counts. Key ResultsEach lineage of bryophytes exhibits a distinct pattern of genome size evolution and prevalence of WGD, with mosses having the most dynamic genome sizes and highest propensity for WGD. We found that 21.3 % of mosses and 13 % of liverworts species have naturally occurring polyploids. In addition, haploid genome size (1C) is most dynamic in the mosses, which includes at least 15 transitions to larger genomes and nine reversals, largely in the orders Dicranales and Hypnales. ConclusionsThere is no correlation between genome size and WGD or between genome size and chromosome number, potentially suggesting rapid genome downsizing following WGD. Given that bryophytes are poikilohydric (desiccation-tolerant) plants, having large genomes might be physiologically prohibitive given the cost to growth and metabolism associated with them. These findings emphasize the unique evolution of the bryophytes broadly and of the hornworts, liverworts and mosses individually, and should therefore serve as impetus for more in-depth experimental studies of genome size evolution and WGD in bryophytes. 

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4. KegAlign: optimizing pairwise alignments with diagonal partitioning

   https://doi.org/10.1186/s13059-025-03830-0  

   Gulhan, A Burak; Burhans, Richard; Harris, Robert; Kandemir, Mahmut; Haeussler, Maximilian; Nekrutenko, Anton (December 2025, Genome Biology)

   Abstract Advances in sequencing and assembly allow the creation of thousands of genome assemblies. However, producing multiple alignments required for their analysis lags behind due to the time-consuming process of pairwise alignment, typically performed by the slow but sensitive tool lastZ. Here, we develop KegAlign, an optimized GPU-enabled pairwise aligner. KegAlign employs a novel diagonal partitioning parallelization strategy and leverages advanced GPU features. It can compute a human/mouse alignment in under 6 h on a GPU-containing node without pre-partitioning, maintaining lastZ-level sensitivity crucial for divergent genomes. KegAlign is available as source code, a Conda package, and a user-friendly Galaxy workflow. 

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5. Mitochondrial genome diversity across the subphylum Saccharomycotina

   https://doi.org/10.3389/fmicb.2023.1268944  

   Wolters, John F.; LaBella, Abigail L.; Opulente, Dana A.; Rokas, Antonis; Hittinger, Chris Todd (November 2023, Frontiers in Microbiology)

   IntroductionEukaryotic life depends on the functional elements encoded by both the nuclear genome and organellar genomes, such as those contained within the mitochondria. The content, size, and structure of the mitochondrial genome varies across organisms with potentially large implications for phenotypic variance and resulting evolutionary trajectories. Among yeasts in the subphylum Saccharomycotina, extensive differences have been observed in various species relative to the model yeastSaccharomyces cerevisiae, but mitochondrial genome sampling across many groups has been scarce, even as hundreds of nuclear genomes have become available. MethodsBy extracting mitochondrial assemblies from existing short-read genome sequence datasets, we have greatly expanded both the number of available genomes and the coverage across sparsely sampled clades. ResultsComparison of 353 yeast mitochondrial genomes revealed that, while size and GC content were fairly consistent across species, those in the generaMetschnikowiaandSaccharomycestrended larger, while several species in the order Saccharomycetales, which includesS. cerevisiae, exhibited lower GC content. Extreme examples for both size and GC content were scattered throughout the subphylum. All mitochondrial genomes shared a core set of protein-coding genes for Complexes III, IV, and V, but they varied in the presence or absence of mitochondrially-encoded canonical Complex I genes. We traced the loss of Complex I genes to a major event in the ancestor of the orders Saccharomycetales and Saccharomycodales, but we also observed several independent losses in the orders Phaffomycetales, Pichiales, and Dipodascales. In contrast to prior hypotheses based on smaller-scale datasets, comparison of evolutionary rates in protein-coding genes showed no bias towards elevated rates among aerobically fermenting (Crabtree/Warburg-positive) yeasts. Mitochondrial introns were widely distributed, but they were highly enriched in some groups. The majority of mitochondrial introns were poorly conserved within groups, but several were shared within groups, between groups, and even across taxonomic orders, which is consistent with horizontal gene transfer, likely involving homing endonucleases acting as selfish elements. DiscussionAs the number of available fungal nuclear genomes continues to expand, the methods described here to retrieve mitochondrial genome sequences from these datasets will prove invaluable to ensuring that studies of fungal mitochondrial genomes keep pace with their nuclear counterparts. 

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