Biology subjects

Moreno-Hagelsieb, G.

Publications and source records attributed to Moreno-Hagelsieb, G..

8 recordsLinked to original sources

bioRxiv2026

Strain-specific higher-order interactions break phylogenetic conservatism in microbial communities

Whether strains of the same species sharing the same ecological role are truly interchangeable has not been directly tested experimentally in communities, where higher-order interactions govern outcomes. Using 79 co-occurring Bacillaceae isolates from the Cuatrocienegas Basin, we combined whole-genome analyses with systematic strain substitutions in BARS, a three-species community in which a resistant strain protects a sensitive strain from an antagonist. Trait conservatism strongly predicted pairwise antagonistic outcomes. Yet across 34 assembled triads, 13 showed rescue beyond pairwise expectations and five showed suppression; single-strain substitutions rarely restored protection, although protection was recovered in one fully reconfigured triad. These outcomes could not be inferred from taxonomic relatedness, pangenomic content or pairwise assays; phylogenetic conservatism thus reaches its limit at the transition from pairwise to higher-order interactions. To explain this limit, we propose that strains behave as non-equivalent biological tiles whose interaction edges must align, a dynamic biological tessellation.

evolutionary biology↗

bioRxiv2026

Phylogenetic correlation between the Type IV Secretion System and HIP1 suggest an adaptation for horizontal gene transfer conserved at the phylum level

Most cyanobacterial genomes are rich in the GCGATCGC octamer, also known as Highly Iterated Palindrome 1 (HIP1). Despite its description over three decades ago, the biological function of this highly abundant sequence is only beginning to be elucidated. HIP1 is recognized by two DNA methylases, DmtA and DmtC, and is characterized by its evolutionary conservation and a quasi-periodic distribution within genomes. However, whether the phylogenetic distribution of HIP1 correlates with the presence of functional categories of protein families remains unknown. Here we investigated whether certain protein families share a phylogenetic distribution with this abundant palindromic sequence across cyanobacterial genomes. Our analysis revealed a strong phylogenetic correlation between several proteins of the Type IV secretion system (T4SS) and the abundance of HIP1. This finding aligns with recent discoveries demonstrating that HIP1 enhances DNA transformation in a methylation-dependent manner in two distinct cyanobacterial species. Consequently, we hypothesize that HIP1 function as a conserved adaptation for horizontal gene transfer (HGT) at the phylum level, potentially by serving as a DNA-uptake recognition sequence in cyanobacteria. Significance statementScientists have long been baffled by the HIP1 sequence, a short, highly common, repetitive DNA pattern found across almost all cyanobacterial genomes. Our study used a whole-genome evolutionary approach and found that the presence of this repetitive pattern is tightly linked to the presence of a cells external DNA uptake system. This tight co-evolutionary relationship suggests that HIP1 isnt just random genomic feature, but a conserved evolutionary adaptation used by the entire cyanobacterial phylum to specifically enhance their ability to acquire new genes from one another.

evolutionary biology↗

bioRxiv2024

Transcription factors across the Escherichia coli pangenome: a 3D perspective

MotivationIdentification of complete sets of transcription factors (TFs) is a foundational step in the inference of genetic regulatory networks. With the availability of high-quality predictions of protein three-dimensional structures (3D), it has become possible to use structural comparisons for the inference of homology beyond what is possible from sequence analyses alone. This work explores the potential to use predicted 3D structures for the identification of TFs in the Escherichia coli pangenome. ResultsComparisons between predicted structures and their experimentally confirmed counterparts confirmed the high-quality of predicted structures, with most 3D structural alignments showing TM-scores well above established structural similarity thresholds, though the quality seemed slightly lower for TFs than for other proteins. As expected, structural similarity decreased with sequence similarity, though most TM-scores still remained above the structural similarity threshold. This was true regardless of the aligned structures being experimental or predicted. Results at the lowest sequence identity levels revealed potential for 3D structural comparisons to extend homology inferences below the "twilight zone" of sequence-based methods. The body of predicted 3D structures covered 99.7% of available proteins from the E. coli pangenome, missing only two of those matching TF domain sequence profiles. Structural analyses increased the inferred TFs in the E. coli pangenome by 18% above the amount obtained with sequence profiles alone.

genomics↗

bioRxiv2024

AnnoView enables large-scale analysis, comparison, and visualization of microbial gene neighborhoods

The analysis and comparison of gene neighborhoods is a powerful approach for exploring microbial genome structure, function, and evolution. Although numerous tools exist for genome visualization and comparison, genome exploration across large genomic databases or user-generated datasets remains a challenge. Here, we introduce AnnoView, a web server designed for interactive exploration of gene neighborhoods across the bacterial and archaeal tree of life. Our server offers users the ability to identify, compare, and visualize gene neighborhoods of interest from 30,238 bacterial genomes and 1,672 archaeal genomes, through integration with the comprehensive GTDB and AnnoTree databases. Identified gene neighborhoods can be visualized using pre-computed functional annotations from different sources such as KEGG, Pfam, and TIGRFAM, or clustered based on similarity. Alternatively, users can upload and explore their own custom genomic datasets in GBK, GFF, or CSV format, or use AnnoView as a genome browser for relatively small genomes (e.g., viruses and plasmids). Ultimately, we anticipate that AnnoView will catalyze biological discovery by enabling user-friendly search, comparison, and visualization of genomic data. AnnoView is available at http://annoview.uwaterloo.ca

bioinformatics↗

bioRxiv2023

Fast genome-based delimitation of Enterobacterales species

Average Nucleotide Identity (ANI) is becoming a standard measure for bacterial species delimitation. However, its calculation can take orders of magnitude longer than fast similarity estimates based on sampling of short nucleotides, compiled into so-called sketches. These estimates are widely used and correlate well with ANI. However, they might not be as accurate. Thus, we compared two sketching programs, mash and dashing, against ANI, in delimiting species among publicly available Esterobacterales genomes. Receiver Operating Characteristic (ROC) curve analysis found all three programs to be highly accurate, with Area Under the Curve (AUC) values of 0.99, indicating almost perfect species discrimination. Subsampling to reduce over-represented species, reduced these AUC values to 0.92. Focused tests with ten genera represented by more than three species, also showed almost identical results for all methods. Shigella showed the lowest AUC values (0.68), followed by Citrobacter (0.80). All other genera, Dickeya, Enterobacter, Escherichia, Klebsiella, Pectobacterium, Proteus, Providencia and Yersinia, produced AUC values above 0.90. The species delimitation thresholds varied, with species distance ranges in a few genera overlapping the genus ranges of other genera. Mash was able to separate the E. coli + Shigella complex into 25 apparent phylogroups. Testing mash for species separation in genera outside Enterobacterales showed AUCs above 0.95, again with different thresholds for species delimitation within each genus. Overall, our results suggest that fast estimates of genome similarity are as good as ANI for species delimitation. Therefore, these fast estimates might suffice for determining the role of genomic similarity in bacterial taxonomy.

bioinformatics↗

bioRxiv2021

ANI, Mash and Dashing equally differentiate between Klebsiella species

Species of the genus Klebsiella are among the most important multidrug resistant human pathogens, though they have been isolated from a variety of environments. Given the need for quickly and accurately classifying newly sequenced Klebsiella genomes, we compared 982 Klebsiella genomes using different species-delimiting measures: Average Nucleotide Identity (ANI), which is becoming a standard for species delimitation, as well as Mash, Dashing, and DNA compositional signatures, which can be run in a fraction of the time required to run ANI. ROC analyses showed equal quality in species delimitation for ANI, Mash and Dashing (AUC: 0.99), followed by DNA signatures (AUC: 0.96). The groups obtained at optimal cutoffs were largely in agreement with species designation. Using optimized cutoffs, we obtained 17 species-level groups using either ANI, Mash, or Dashing, all containing the same genomes, unlike DNA signatures which broke the dataset into 38 groups. Further use of Mash to map species after adding draft genomes to the dataset also showed excellent results (AUC: 0.99), producing a total of 28 Klebsiella species in the publicly available genome collection. The ecological niches of Klebsiella strains were found to neither be related to species delimitation, nor to protein functional content, suggesting that a single Klebsiella species can have a wide repertoire of ecological functions.

genomics↗

bioRxiv2020

Progress in quickly finding orthologs as reciprocal best hits

IntroductionFinding orthologs remains an important bottleneck in comparative genomics analyses. While the authors of software for the quick comparison of protein sequences evaluate the speed of their software and compare their results against the most usual software for the task, it is not common for them to evaluate their software for more particular uses, such as finding orthologs as reciprocal best hits (RBH). Here we compared RBH results, between prokaryotic genomes, obtained using software that runs faster than blastp. Namely, lastal, diamond, and MMseqs2. ResultsWe found that lastal required the least time to produce results. However, it yielded fewer results than any other program when comparing evolutionarily distant genomes. The program producing the most similar number of RBH as blastp was MMseqs2. This program also resulted in the lowest error estimates among the programs tested. The results with diamond were very close to those obtained with MMseqs2, with diamond running faster. Our results suggest that the best of the programs tested was diamond, ran with the "sensitive" option, which took 7% of the time as blastp to run, and produced results with lower error rates than blastp. AvailabilityA program to obtain reciprocal best hits using the software we tested is maintained at https://github.com/Computational-conSequences/SequenceTools

bioinformatics↗

bioRxiv2018

Non-synonymous to synonymous substitutions suggest that orthologs tend to keep their functions, while paralogs are a source of functional novelty

Orthologs diverge after lineage separation events and paralogs after gene duplications. Thus, orthologs are expected to remain more functionally coherent across lineages, while paralogs have been proposed as a source of new functions. Because protein functional divergence follows from non-synonymous substitutions, we performed an analysis based on the ratio of non-synonymous to synonymous substitutions (dN/dS), as proxy for functional divergence. We used five working definitions of orthology, including reciprocal best hits (RBH), among other definitions based on network analyses and clustering. The results showed that orthologs, by all definitions tested, had values of dN/dS noticeably lower than those of paralogs, suggesting that, as a group, orthologs tend to be more functionally stable than paralogs. The differences in dN/dS ratios remained suggesting the functional stability of orthologs after eliminating gene comparisons with potential problems, such as genes with high codon usage biases, low coverage of either of the aligned sequences, or sequences with very high similarities. Separation by percent identity of the encoded proteins showed that the differences between the dN/dS ratios of orthologs and paralogs were more evident at high sequence identity, less so as identity dropped. While the last results partially explained the differences between dN/dS ratios of the two groups as being related to differences in protein identity, they also suggested that paralogs undergo functional divergence relatively early after duplication. Our analyses indicate that choosing orthologs as probably functionally coherent remains the right approach in comparative genomics.

evolutionary biology↗