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bioRxiv2022

A collaborative approach to improving representation in viral genomic surveillance

The lack of routine viral genomic surveillance delayed the initial detection of SARS-CoV-2, allowing the virus to spread unfettered at the outset of the U.S. epidemic. Over subsequent months, poor surveillance enabled variants to emerge unnoticed. Against this backdrop, long-standing social and racial inequities have contributed to a greater burden of cases and deaths among minority groups. To begin to address these problems, we developed a new variant surveillance model geared toward building microbial genome sequencing capacity at universities in or near rural areas and engaging the participation of their local communities. The resulting genomic surveillance network has generated more than 1,000 SARS-CoV-2 genomes to date, including the first confirmed case in northeast Louisiana of Omicron, and the first and sixth confirmed cases in Georgia of the emergent BA.2.75 and BQ.1.1 variants, respectively. In agreement with other studies, significantly higher viral gene copy numbers were observed in Delta variant samples compared to those from Omicron BA.1 variant infections, and lower copy numbers were seen in asymptomatic infections relative to symptomatic ones. Collectively, the results and outcomes from our collaborative work demonstrate that establishing genomic surveillance capacity at smaller academic institutions in rural areas and fostering relationships between academic teams and local health clinics represent a robust pathway to improve pandemic readiness. Author summaryGenomic surveillance involves decoding a pathogens genetic code to track its spread and evolution. During the pandemic, genomic surveillance programs around the world provided valuable data to scientists, doctors, and public health officials. Knowing the complete SARS-CoV-2 genome has helped detect the emergence of new variants, including ones that are more transmissible or cause more severe disease, and has supported the development of diagnostics, vaccines, and therapeutics. The impact of genomic surveillance on public health depends on representative sampling that accurately reflects the diversity and distribution of populations, as well as rapid turnaround time from sampling to data sharing. After a slow start, SARS-CoV-2 genomic surveillance in the United States grew exponentially. Despite this, many rural regions and ethnic minorities remain poorly represented, leaving significant gaps in the data that informs public health responses. To address this problem, we formed a network of universities and clinics in Louisiana, Georgia, and Mississippi with the goal of increasing SARS-CoV-2 sequencing volume, representation, and equity. Our results demonstrate the advantages of rapidly sequencing pathogens in the same communities where the cases occur and present a model that leverages existing academic and clinical infrastructure for a powerful decentralized genomic surveillance system.

microbiology↗

bioRxiv2022

GSearch: Ultra-Fast and Scalable Microbial Genome Search by combining Kmer Hashing with Hierarchical Navigable Small World Graphs

Genome search and/or classification is a key step in microbiome studies and has recently become more challenging due to the increasing number of available (reference) genomes and the fact that traditional methods do not scale well with large databases. By combining k-mer hashing-based probabilistic data structures (e.g., (Prob/Super/Densified)-MinHash or SetSketch) to estimate genomic distance, with a graph-based nearest neighbor search algorithm (called Hierarchical Navigable Small World Graphs, or HNSW), we created a new data structure and developed an associated computer program, GSearch, that is orders of magnitude faster than alternative tools while maintaining high accuracy and low memory usage. For example, GSearch can identify/classify 8,000 query genomes against all available microbial or viral genomes (n=[~]318,000 or [~]3,000,000) within a few minutes on a personal laptop, using only [~]6GB of memory or less (e.g., 2.5G via SetSketch). Notably, GSearch will be even faster compared to other tools with even larger database size due to O(log(N)) time complexity and will scale well with billions of database genomes based on a database splitting strategy. Further, GSearch implements a three-step classification pipeline that accounts for the degree of novelty of query genomes relative to the database genome to maximize specificity and sensitivity. Therefore, GSearch solves a major bottleneck of microbiome studies that require genome search and/or classification of microbial or viral genomes. GSearch is available at: https://github.com/jean-pierreBoth/gsearch

bioinformatics↗

bioRxiv2022

Extreme genome diversity and cryptic speciation in a harmful algal bloom forming eukaryote

Harmful algal blooms (HABs) of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Strains of P. parvum vary in the toxins they produce and in other physiological traits associated with HABs, but the genetic basis for this variation is unknown. To investigate genome diversity in this morphospecies, we generated genome assemblies for fifteen phylogenetically and geographically diverse strains of P. parvum including Hi-C guided, near-chromosome level assemblies for two strains. Comparative analysis revealed considerable DNA content variation between strains, ranging from 115 Mbp to 845 Mbp. Strains included haploids, diploids, and polyploids, but not all differences in DNA content were due to variation in genome copy number. Haploid genome size between strains of different chemotypes differed by as much as 243 Mbp. Syntenic and phylogenetic analyses indicate that UTEX 2797, a common laboratory strain from Texas, is a hybrid that retains two phylogenetically distinct haplotypes. Investigation of gene families variably present across strains identified several functional categories associated with metabolism, including candidates for the biosynthesis of toxic metabolites, as well as genome size variation, including recent proliferations of transposable elements. Together, our results indicate that P. parvum is comprised of multiple cryptic species. These genomes provide a robust phylogenetic and genomic framework for investigations into the eco-physiological consequences of the intra- and inter-specific genetic variation present in P. parvum and demonstrate the need for similar resources for other HAB-forming morphospecies. SIGNIFICANCE STATEMENTHarmful algal blooms (HABs) are a global concern. Efforts to understand the genetic basis of traits associated with the success of HAB-forming species are limited by a dearth of genomic resources. In this paper we present genomes for fifteen strains of Prymnesium parvum, a toxic alga that causes ecosystem and societally disruptive HABs around the world. We uncover an unprecedented amount of sequence-level, gene family, and genome architecture evolution in P. parvum and provide evidence for both cryptic speciation and hybridization. These results illustrate how both inter- and intraspecific genetic variation can be dramatically underestimated in a protist morphospecies. More work is needed to understand the eco-physiological consequences of hidden genetic diversity in P. parvum and HAB-forming species more generally.

evolutionary biology↗

bioRxiv2022

Microbial and Viral Genome and Proteome Nitrogen Demand Varies Across Multiple Spatial Scales Within a Marine Oxygen Minimum Zone

Nutrient availability can significantly influence microbial genomic and proteomic streamlining, for example by selecting for lower nitrogen to carbon ratios. Oligotrophic open ocean microbes have streamlined genomic nitrogen requirements relative to their counterparts in nutrient-rich coastal waters. However, steep gradients in nutrient availability occur at meter- and even micron-level spatial scales. It is unclear if such gradients also structure genomic and proteomic stoichiometry. Focusing on the eastern tropical North Pacific oxygen minimum zone (OMZ), we use comparative metagenomics to examine how nitrogen availability shapes microbial and viral genome properties along the vertical gradient across the OMZ and between two size fractions distinguishing free-living versus particle-associated microbes. We find a substantial increase in nitrogen content of encoded proteins in particle-associated over free-living bacteria and archaea across nitrogen availability regimes over depth. Within each size-fraction, we find that bacterial and viral genomic nitrogen tends to increase with increasing nitrate concentrations with depth. In contrast to cellular genes, the nitrogen content of virus proteins does not differ between size fractions. We identified arginine as a key amino acid in modulating the C:N ratio of core genes for bacteria, archaea, and viruses. Functional analysis reveals that particle-associated bacterial metagenomes are enriched for genes involved in arginine metabolism and organic nitrogen compound catabolism. Our results are consistent with nitrogen streamlining in both cellular and viral genomes on spatial scales of meters to microns. These effects are similar in magnitude to those previously reported across scales of thousands of kilometers. IMPORTANCEThe genomes of marine microbes can be shaped by nutrient cycles, with ocean-scale gradients in nitrogen availability known to influence microbial amino acid usage. It is unclear, however, how genomic properties are shaped by nutrient changes over much smaller spatial scales, for example along the vertical transition into oxygen minimum zones (OMZs) or from the exterior to interior of detrital particles. Here, we measure protein nitrogen usage by marine bacteria, archaea, and viruses using metagenomes from the nitracline of the eastern tropical North Pacific OMZ including both particle-associated and non-associated biomass. Our results show higher genomic and proteomic nitrogen content in particle-associated microbes and at depths with higher nitrogen availability for cellular and viral genomes. This discovery suggests that stoichiometry influences microbial and viral evolution across multiple scales, including the micro- to millimeter scale associated with particle-associated versus free-living lifestyles.

microbiology↗

bioRxiv2022

Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine

The annotation of microRNAs, an important class of post-transcriptional regulators, depends on the availability of transcriptomics data and expert knowledge. This led to a large gap between novel genomes made available and high-quality microRNA complements. Using >16,000 microRNAs from the manually curated microRNA gene database MirGeneDB, we generated trained covariance models for all conserved microRNA families. These models are available in MirMachine, our new tool for the annotation of conserved microRNA complements from genomes only. We successfully applied MirMachine to a wide range of animal species, including those with very large genomes, additional genome duplications and extinct species, where smallRNA sequencing will be hard to achieve. We further describe a microRNA score of expected microRNAs that can be used to assess the completeness of genome assemblies. MirMachine closes a long-persisting gap in the microRNA field facilitating automated genome annotation pipelines and deeper studies on the evolution of genome regulation, even in extinct organisms. HighlightsO_LIAn annotation pipeline using trained covariance models of microRNA families C_LIO_LIEnables massive parallel annotation of microRNA complements of genomes C_LIO_LIMirMachine creates meaningful annotations for very large and extinct genomes C_LIO_LImicroRNA score to assess genome assembly completeness C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/517654v2_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@1ee2bf1org.highwire.dtl.DTLVardef@18719c1org.highwire.dtl.DTLVardef@abcfb6org.highwire.dtl.DTLVardef@1d1c368_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2022

Haplotype resolved chromosome level genome assembly of Citrus australis reveals disease resistance and other citrus specific genes

Recent advances in genome sequencing and assembly techniques have made it possible to achieve chromosome level reference genomes for citrus. Relatively few genomes have been anchored at the chromosome level and/or are haplotype phased, with the available genomes of varying accuracy and completeness. We now report a phased high-quality chromosome level genome assembly for an Australian native citrus species; Citrus australis (round lime) using highly accurate PacBio HiFi long reads, complemented with Hi-C scaffolding. Hifiasm with Hi-C integrated assembly resulted in a 331 Mb genome of C. australis with two haplotypes of nine pseudochromosomes with an N50 of 36.3 Mb and 98.8% genome assembly completeness (BUSCO). Repeat analysis showed that more than 50% of the genome contained interspersed repeats. Among them, LTR elements were the predominant type (21.0%), of which LTR Gypsy (9.8 %) and LTR copia (7.7 %) elements were the most abundant repeats. A total of 29,464 genes and 32,009 transcripts were identified in the genome. Of these, 28,222 CDS (25,753 genes) had BLAST hits and 21,401 CDS (75.8%) were annotated with at least one GO term. Citrus specific genes for antimicrobial peptides, defense, volatile compounds and acidity regulation were identified. This chromosome scale, and haplotype resolved C. australis genome will facilitate the study of important genes for citrus breeding and will also allow the enhanced definition of the evolutionary relationships between wild and domesticated citrus species.

plant biology↗

bioRxiv2023

HiCLift: A fast and efficient tool for converting chromatin interaction data between genome assemblies

MotivationWith the continuous effort to improve the quality of human reference genome and the generation of more and more personal genomes, the conversion of genomic coordinates between genome assemblies is critical in many integrative and comparative studies. While tools have been developed for such task for linear genome signals such as ChIP-Seq, no tool exists to convert genome assemblies for chromatin interaction data, despite the importance of three-dimensional (3D) genome organization in gene regulation and disease. ResultsHere, we present HiCLift, a fast and efficient tool that can convert the genomic coordinates of chromatin contacts such as Hi-C and Micro-C from one assembly to another, including the latest T2T genome. Comparing with the strategy of directly re-mapping raw reads to a different genome, HiCLift runs on average 42 times faster (hours vs. days), while outputs nearly identical contact matrices. More importantly, as HiCLift does not need to re-map the raw reads, it can directly convert human patient sample data, where the raw sequencing reads are sometimes hard to acquire or not available. AvailabilityHiCLift is publicly available at https://github.com/XiaoTaoWang/HiCLift.

bioinformatics↗

bioRxiv2023

NetSyn: genomic context exploration of protein families

Background: The growing availability of large prokaryotic genomic datasets presents an opportunity to discover new metabolic pathways and enzymatic reactions useful for industrial or synthetic biological applications. Efforts to identify new enzyme functions in this vast number of sequences cannot be achieved without bioinformatics tools and the development of new strategies. Standard methods for assigning a biological function to a gene are based on sequence similarity. However, complementary approaches rely on mine databases to identify conserved gene clusters (i.e. syntenies). In prokaryotic genomes, genes involved in the same pathway are frequently encoded in a single locus with an operonic organisation. This genomic context conservation is considered as a reliable indicator of functional relationships, and is therefore a promising approach for improving the gene function prediction. Methods. Here we present NetSyn (Network Synteny), a tool to group protein sequences based on the conservation of their genomic context rather than solely on sequence similarity. From a list of protein sequence identifiers, NetSyn searches corresponding genome entries to retrieve neighboring genes. Corresponding protein sequences are grouped into families to define homology relationships and compute a synteny conservation score between the different extracted genomic contexts. A network is then created in which the nodes represent the input proteins and the edges indicate that two proteins share a conserved synteny. Finally, the network is partitioned into clusters grouping proteins with similar genomic contexts, using a community detection algorithm. Results. As a proof of concept, we used NetSyn on two different datasets. The first one is the BKACE protein family (formerly named DUF849) which has previously been divided into isofunctional sub-families. NetSyn was able to go a step further by providing additional sub-families beyond those already described. The second dataset corresponds to a set of non-homologous proteins belonging to three different glycoside hydrolase (GH) families. These GHs are known to work cooperatively in a Polysaccharide-Utilization Loci (PUL) and are therefore grouped together in the same genomic contexts. NetSyn was able to identify a locus grouping 3 GHs, involved in the degradation of xyloglucan, in 162 prokaryotic genomes. Discussion. By highlighting conserved synteny in distantly related prokaryotic species, NetSyn enables functional links between proteins to be established beyond sequence similarity alone. We showed that NetSyn is efficient for exploring large prokaryotic protein families, enabling the definition of isofunctional groups and the identification of functional interactions between non-homologous enzymes. These features enable the prediction of new genomic structures that have not yet been experimentally characterized. Finally, NetSyn is also useful for pinpointing annotation errors that have been propagated across databases, and for suggesting annotations on proteins lacking functional prediction. NetSyn is freely available at https://github.com/labgem/netsyn.

bioinformatics↗

bioRxiv2023

Genus-Wide Genomic Characterization of Macrococcus: Insights into Evolution, Population Structure, and Functional Potential

Macrococcus species have been isolated from a range of mammals and mammal-derived food products. While they are largely considered to be animal commensals, Macrococcus spp. can be opportunistic pathogens in both veterinary and human clinical settings. This study aimed to provide insight into the evolution, population structure, and functional potential of the Macrococcus genus, with an emphasis on antimicrobial resistance (AMR) and virulence potential. All high-quality, publicly available Macrococcus genomes (n = 104, accessed 27 August 2022), plus six South African genomes sequenced here (two strains from bovine clinical mastitis cases and four strains from beef products), underwent taxonomic assignment (using four different approaches), AMR determinant detection (via AMRFinderPlus), and virulence factor detection (using DIAMOND and the core Virulence Factor Database). Overall, the 110 Macrococcus genomes were of animal commensal, veterinary clinical, food-associated (including food spoilage), and environmental origins; five genomes (4.5%) originated from human clinical cases. Notably, none of the taxonomic assignment methods produced identical results, highlighting the potential for Macrococcus species misidentifications. The most common predicted antimicrobial classes associated with AMR determinants identified across Macrococcus included macrolides, beta-lactams, and aminoglycosides (n = 81, 61, and 44 of 110 genomes; 73.6, 55.5, and 40.0%, respectively). Genes showing homology to Staphylococcus aureus exoenzyme aureolysin were detected across multiple species (using 90% coverage, n = 40 and 77 genomes harboring aureolysin-like genes at 60% and 40% amino acid [AA] identity, respectively). Staphylococcus aureus Panton-Valentine leucocidin toxin-associated lukF-PV and lukS-PV homologs were identified in eight M. canis genomes ([≥]40% AA identity, >85% coverage). Using a method that delineates populations using recent gene flow (PopCOGenT), two species (M. caseolyticus and M. armenti) were composed of multiple within-species populations. Notably, M. armenti was partitioned into two populations, which differed in functional potential (e.g., one harbored beta-lactamase family, type II toxin-antitoxin system, and stress response proteins, while the other possessed a Type VII secretion system; PopCOGenT P < 0.05). Overall, this study leverages all publicly available Macrococcus genomes in addition to newly sequenced genomes from South Africa to identify genomic elements associated with AMR or virulence potential, which can be queried in future experiments.

microbiology↗

bioRxiv2023

A new Plasmodium vivax reference genome for South American isolates

BackgroundPlasmodium vivax is the second most important cause of human malaria worldwide, and accounts for the majority of malaria cases in South America. A high-quality reference genome exists for Papua Indonesia (PvP01) and Thailand (PvW1), but is lacking for South America. A reference genome specifically for South America would be beneficial though, as P. vivax is a genetically diverse parasite with geographical clustering. ResultsThis study presents a new high-quality assembly of a South American P. vivax isolate, referred to as PvPAM. The genome was obtained from a low input patient sample from the Peruvian Amazon and sequenced using PacBio technology, resulting in a highly complete assembly with 6497 functional genes. Telomeric ends were present in 17 out of 28 chromosomal ends, and additional (sub)telomeric regions are present in 12 unassigned contigs. A comparison of multigene families between PvPAM and the PvP01 genome revealed remarkable variation in vir genes, and the presence of merozoite surface proteins (MSP) 3.6 and 3.7. Three dhfr and dhps drug resistance associated mutations are present in PvPAM, similar to those found in other Peruvian isolates. Mapping of publicly available South American whole genome sequencing (WGS) data to PvPAM resulted in significantly fewer variants and truncated reads compared to the use of PvP01 or PvW1 as reference genomes. To minimize the number of core genome variants in non-South American samples, PvW1 is most suited for Southeast Asian isolates, both PvPAM and PvW1 are suited for South Asian isolates, and PvPAM is recommended for African isolates. Interestingly, non-South American samples still contained the least subtelomeric variants when mapped to PvPAM, indicating high quality of the PvPAM subtelomeric regions. ConclusionsOur findings show that the PvPAM reference genome more accurately represents South American P. vivax isolates in comparison to PvP01 and PvW1. In addition, PvPAM has a high level of completeness, and contains a similar number of annotated genes as PvP01 or PvW1. The PvPAM genome therefore will be a valuable resource to improve future genomic analyses on P. vivax isolates from the South American continent.

genetics↗

bioRxiv2023

Deep learning-based survival prediction using DNA methylation-derived 3D genomic information

Three-dimensional (3D) genome states are closely related to cancer development. Nonetheless, the 3D genome information has not been clinically utilized to the best of our knowledge, due to the costly production of Hi-C data which is a manifest source of 3D genome information. Therefore, there is a need for a novel metric computable from a 3D genome-related data which is more easily accessible for the clinical utilization of 3D genome information. We here propose a method to extract 3D genome-aware epigenetic features from DNA methylation data and use these features for a deep learning-based survival prediction. These features are derived from the 3D genome structures which are rebuilt from the DNA methylation data in an individual level. The results showed that usage of 3D genome-aware features contributed to more accurate risk prediction across seven cancer types, suggesting the effectiveness of the knowledge about 3D genome structure embedded in these features. The deeper biological investigation revealed that altered DNA methylation level in risk-high group could be related to the anomalously activated genes involved in cancer-related pathways. Altogether, the risks predicted from 3D genome-aware epigenetic features showed its significance as a survival predictor in seven cancer types, along with its biological importance.

bioinformatics↗

bioRxiv2023

The Genetics of Aerotolerant Growth in a Naturally Reduced Genome Alphaproteobacterium

Reduced genome bacteria are genetically simplified systems that facilitate biological study and industrial use. The free-living Alphaproteobacterium, Zymomonas mobilis, has a naturally reduced genome containing fewer than 2000 protein coding genes. Despite its small genome, Z. mobilis thrives in diverse conditions including the presence or absence of atmospheric oxygen. However, insufficient characterization of essential and conditionally essential genes has limited broader adoption of Z. mobilis as a model Alphaproteobacterium. Here, we use genome-scale CRISPRi-seq to systematically identify and characterize Z. mobilis genes that are conditionally essential for aerotolerant or anaerobic growth, or are generally essential across both conditions. Comparative genomics revealed that the essentiality of most "generally essential" genes was shared between Z. mobilis and other Alphaproteobacteria, validating Z. mobilis as reduced genome model. Among conditionally essential genes, we found that the DNA repair gene, recJ, was critical only for aerobic growth but reduced the mutation rate under both conditions. Further, we show that genes encoding the F1FO ATP synthase and Rnf respiratory complex are required for anaerobic growth of Z. mobilis. Combining CRISPRi partial knockdowns with metabolomics and membrane potential measurements, we determined that the ATP synthase generates membrane potential that is consumed by Rnf to power downstream processes. Rnf knockdown strains accumulated isoprenoid biosynthesis intermediates, suggesting a key role for Rnf in powering essential biosynthetic reactions. Our work establishes Z. mobilis as a streamlined model for alphaproteobacterial genetics, has broad implications in bacterial energy coupling, and informs Z. mobilis genome manipulation for optimized production of valuable isoprenoid-based bioproducts. ImportanceThe inherent complexity of biological systems is a major barrier to our understanding of cellular physiology. Bacteria with markedly fewer genes than their close relatives, or reduced genome bacteria, are promising biological models with less complexity. Reduced genome bacteria can also have superior properties for industrial use, provided the reduction does not overly restrict strain robustness. Naturally reduced genome bacteria, such as the Alphaproteobacterium, Zymomonas mobilis, have fewer genes but remain environmentally robust. In this study, we show that Z. mobilis is a simplified genetic model for Alphaproteobacteria, a class with important impacts on the environment, human health, and industry. We also identify genes that are only required in the absence of atmospheric oxygen, uncovering players that maintain and utilize the cellular energy state. Our findings have broad implications for the genetics of Alphaproteobacteria and industrial use of Z. mobilis to create biofuels and bioproducts.

genetics↗

bioRxiv2023

Intra- and interspecific variations in genome sizes of Agaricia corals from Curacao

Genome size is a fundamental biological trait that is known to exhibit high diversity among eukaryotic species, but its intraspecific diversity has only scarcely been studied to date. In scleractinian corals, genome size data are only available for a few species. In this study, intra- and interspecific variations in genome size of the coral genus Agaricia collected from Curacao were investigated. Morphology was congruent with genetic analyses of the nuclear markers internal transcribed spacer 2 (ITS2) and L-threonine 3-dehydrogenase (TDH) in delimiting three Agaricia species among our samples. A refined Feulgen Image Analysis Densitometry (FIAD) protocol yielded genome sizes that ranged from 0.359 pg to 0.593 pg within this genus (a 1.7-fold range). The highest intraspecific variation in genome size was recorded in the depth-generalist A. lamarcki (1.5-fold range), followed by the depth specialist A. humilis (1.4-fold range) and A. agaricites (1.3-fold range), the species with an intermediate depth distribution. The mean genome size of A. agaricites (0.495 pg) was significantly larger than that of A. lamarcki (0.448 pg) and A. humilis (0.434 pg). No correlation between average genome size and nucleotide polymorphism{pi} was detected, but we found an almost linear correlation between intraspecific variance of genome size and{pi} of ITS2 (Pearsons r = 0.984, p = 0.113). Genome size and collection depths of both A. lamarcki (Pearsons r = 0.328, p = 0.058) and A. agaricites (Pearsons r = -0.270, p = 0.221) were also not significantly associated. To our knowledge, this study provides the first account of intraspecific variation in corals; the apparent correlation detected between the nucleotide polymorphism of a species and the variance of its genome size will have to be tested using a larger taxonomic spectrum of scleractinian corals as well as in other groups of animals.

evolutionary biology↗

bioRxiv2023

Recent secondary contact, genome-wide admixture, and limited introgression of neo-sex chromosomes between two Pacific island bird species

Secondary contact between closely related taxa represents a "moment of truth" for speciation. Removal of geographic barriers allows us to test the strength of reproductive isolation that evolved in allopatry and identify the genetic, behavioral, and/or ecological barriers that separate species in sympatry. Sex chromosomes are known to rapidly accumulate differences between species, an effect that may be exacerbated for neo-sex chromosomes because they are regions of the genome that have recently become linked to sex chromosomes and are transitioning from autosomal to sex-specific inheritance. Two closely related bird species in the honeyeater family -- Myzomela cardinalis and Myzomela tristrami -- carry neo-sex chromosomes and have come into recent secondary contact in the Solomon Islands after being isolated for [~]3 my. Hybrids of these two species have been observed in sympatry for at least 100 years. To determine the genetic consequences of hybridization, we use population genomic analyses of individuals sampled in allopatry and sympatry to characterize gene flow in the contact zone. Using genome-wide estimates of diversity, differentiation, and divergence, we find that the degree and direction of introgression varies dramatically across the genome. Autosomal introgression is bidirectional, with phenotypic hybrids and phenotypic parentals of both species showing admixed ancestry. On the sex and neo-sex chromosomes, the story is different. Introgression of Z is limited and neo-Z sequence shows no evidence of introgression, whereas introgression of W and neo-W is strong but highly asymmetric, moving only from the invasive M. cardinalis to the resident M. tristrami. Thus, reproductive isolation is incomplete, but sex and neo-sex chromosome regions have prevented gene flow in one (W/neo-W) or both (Z/neo-Z) directions. The recent contact between previously isolated species indicates that hybridization may permit gene flow between taxa in some genomic regions, but species divergence can be maintained by barriers to gene flow associated with rapidly evolving sex-linked regions of the genome. Author SummaryWhen a new species colonizes an island and interacts with a closely related native species, we are provided with a rare opportunity to identify the factors that keep species distinct and the consequences of interbreeding. Regions of the genome that evolve rapidly or influence mate choice may be especially likely to act as barriers to gene flow. The red Myzomela cardinalis, birds in the honeyeater family, have recently arrived to Makira in the Solomon Islands, joining the endemic, all black Myzomela tristrami. We used population genomic analyses of individuals in geographic isolation, as well as those in geographic contact with the other species, to understand the history of these two species and the consequences of their recent range overlap on Makira. We found that regions of the genome that are sex-specific (i.e., sex chromosomes) were either limited in their ability to move between species, or only moved in one direction, from the invading M. cardinalis to the native M. tristrami. This work highlights how certain regions of the genome may be especially important in defining species boundaries and the generation and maintenance of biodiversity.

evolutionary biology↗

bioRxiv2023

Modeling the mosaic structure of bacterial genomes to infer their evolutionary history

The timing and phylogeny of bacterial evolution is difficult to reconstruct because of a scarce fossil record, deep genomic divergences and complexities associated with molecular clocks. Studying bacterial evolutionary history using rich and rapidly accumulating genomic data requires accurate modeling of genome evolution, taking into account that different parts of bacterial genomes have different history. In particular, along the genome, different loci are subject to different selective pressure. In addition, some are horizontally transferred from one bacterium to another, resulting in a mosaic-like genome structure. An important technical aspect is that loci with high effective mutation rates can diverge beyond the aligner detection limit, biasing the genome-wide divergence estimate towards more conserved loci. Therefore, the genome-wide molecular clock cannot be directly applied to study bacterial evolutionary history. In this article, we propose a novel method to gain insight into bacterial evolution based on statistical properties of genomic sequences comparisons. The length distribution of the sequence matches is shaped by the effective mutation rates of different loci, by the horizontal transfers and by the aligner sensitivity. Based on these inputs we build a model and demonstrate that it accounts for the empirically observed distributions, taking the Enterobacteriaceae family as an example. Using the model and the empirical data we fit the evolutionary parameters: time divergences and horizontal transfer rates. Based on the estimated time divergences we build a time-calibrated phylogenetic tree, demonstrating the accuracy of the method and its ability to unravel vertical and horizontal transfers in bacterial genomes.

evolutionary biology↗

bioRxiv2023

General remarks of the secondary promoter element regulating the genome replication of paramyxo- and filoviruses

Paramyxo- and filovirus genomes are equipped with bipartite promoters at their 3 ends to initiate RNA synthesis. The two elements, the primary promoter element 1 (PE1) and the secondary promoter element 2 (PE2), are separated by a spacer region that must be precisely a multiple of six nucleotides, indicating these viruses are related to the "rule of six". However, our knowledge of PE2 has been limited to a narrow spectrum of virus species. In this study, a comparative analysis of 1,647 paramyxoviral genomes from a public database revealed that the paramyxovirus PE2 can be clearly categorized into two distinct subcategories: one marked by C repeats at every six bases (exclusive to the subfamily Orthoparamyxovirinae), and another characterized by CG repeats every six bases (observed in the subfamilies Avulavirinae and Rubulavirinae). This unique pattern collectively mirrors the evolutionary lineage of these subfamilies. Furthermore, we showed that the PE2 of the Rubulavirinae, with the exception of mumps virus, serves as part of the gene-coding region. This may be due to the fact that the Rubulavirinae is the only paramyxovirus that cannot propagate without RNA editing occurring. Zaire ebolavirus has eight sequential uracil (U) repeats every six bases within its genomic promoter. We showed that a minimum of four sequential U-containing hexamer repeats is imperative for genome replication. This discovery led to the identification of such quadruplet U-containing hexamer repeats within the genomic and antigenomic promoters of other viruses within the family Filoviridae. SignificanceThe genomic intricacies of paramyxo- and filoviruses are highlighted by the bipartite promoters--PE1 and PE2--at their 3 termini. The spacer region between these elements follows the "rule of six", crucial for genome replication. By a comprehensive analysis of paramyxoviral genome sequences, we identified distinct subcategories of PE2 based on C and CG repeats that were specific to Orthoparamyxovirinae and Avulavirinae/Rubulavirinae, respectively, mirroring their evolutionary lineages. Notably, the PE2 of Rubulavirinae is integrated in the gene-coding region, a unique trait potentially linked to its complete dependence on RNA editing for virus growth. This study also focused on the PE2 sequences in filovirus genomes. In filoviruses, four consecutive U-containing hexamer repeats appeared to be critical for their genome replication.

microbiology↗

bioRxiv2023

Impact of homologous recombination on core genome evolution and host adaptation of Pectobacterium parmentieri

Homologous recombination is a major force mechanism driving bacterial evolution, host adaptability and acquisition of novel virulence traits. Pectobacterium parmentieri is a plant bacterial pathogen distributed worldwide, primarily affecting potatoes, by causing soft rot and blackleg diseases. The goal of this investigation was to understand the impact of homologous recombination on the genomic evolution of P. parmentieri. Analysis of P. parmentieri genomes using Roary revealed a dynamic pan-genome with 3,742 core genes and over 55% accessory genome variability. Bayesian population structure analysis identified seven lineages, indicating species heterogeneity. ClonalFrameML analysis displayed 5,125 recombination events, with the lineage 4 exhibiting the highest events. FastGEAR analysis identified 486 ancestral and 941 recent recombination events ranging 43 bp - 119 kb and 36 bp - 13.96 kb, respectively, suggesting ongoing adaptation. Notably, 11% (412 genes) of the core genome underwent recent recombination, with lineage 1 as the main donor. The prevalence of recent recombination (double compared to ancient) events implies continuous adaptation, possibly driven by global potato trade. Recombination events were found in vital cellular processes (DNA replication, DNA repair, RNA processing, homeostasis, and metabolism), pathogenicity determinants (type secretion systems, cell-wall degrading enzymes, iron scavengers, lipopolysaccharides, flagellum, etc.), antimicrobial compounds (phenazine and colicin) and even CRISPR-Cas genes. Overall, these results emphasize the role of homologous recombination in P. parmentieris evolutionary dynamics, influencing host colonization, pathogenicity, adaptive immunity, and ecological fitness. SignificanceThis study explores the influence of homologous recombination on the genomic evolution of the globally distributed plant pathogen P. parmentieri, characterized by highly heterogenous strains from various global locations. Our findings reveal diverse recombinogenic patterns within the core genomes of P. parmentieri isolates, notably in genomic loci associated with vital cell functions, pathogenicity determinants, and CRISPR-Cas genes. These findings highlight the role of homologous recombination in shaping the genomes of P. parmentieri and impacting its phytopathogenic lifestyle. Additionally, the data suggest a potential role of recombination in the ecological adaptation of this species across different climates, providing insights into the worldwide presence of P. parmentieri. This study represents a pioneering exploration of the impact of homologous recombination on the dynamic evolutionary genomics of the soft rot-causing bacterium P. parmentieri.

evolutionary biology↗

bioRxiv2024

Genomic background sequences systematically outperform synthetic ones in de novo motif discovery for ChIP-seq data

Efficient de novo motif discovery from the results of wide-genome mapping of transcription factor binding sites (ChIP-seq) is dependent on the choice of background nucleotide sequences. The foreground sequences (peaks) represent not only specific motifs of target transcription factors, but also the motifs overrepresented throughout the genome, such as simple sequence repeats. We performed a massive comparison of the synthetic and genomic approaches to generate background sequences for de novo motif discovery. The synthetic approach shuffled nucleotides in peaks, while in the genomic approach randomly selected sequences from the reference genome or only from gene promoters according to the fraction of A/T nucleotides in each sequence. We compiled the benchmark collections of ChIP-seq datasets for mammalian and Arabidopsis, and performed de novo motif discovery. We showed that the genomic approach has both more robust detection of the known motifs of target transcription factors and more stringent exclusion of the simple sequence repeats as possible non-specific motifs. The advantage of the genomic approach over the synthetic one was greater in plants compared to mammals. We developed the AntiNoise web service (https://denovosea.icgbio.ru/antinoise/) which implements a genomic approach to extract genomic background sequences for twelve eukaryotic genomes.

bioinformatics↗