Biology subjects

Mixao, V.

Publications and source records attributed to Mixao, V..

6 recordsLinked to original sources

bioRxiv2025

cgDist: An Enhanced Algorithm for Efficient Calculation of pairwise SNP and InDel differences from Core Genome Multilocus Sequence Typing

Bacterial genomic surveillance requires balancing computational efficiency with genetic resolution for effective outbreak investigation. Traditional cgMLST distance calculations treat all allelic differences as equivalent units, potentially obscuring nucleotide-level variation critical for source attribution. While SNP-based methods provide enhanced resolution, their computational requirements limit routine deployment in surveillance laboratories. We present cgDist, an algorithm that bridges this resolution gap by calculating nucleotide-level distances directly from cgMLST allelic profiles. The unified cache architecture stores comprehensive alignment statistics, enabling multiple distance calculation modes without redundant computation and supporting both dataset-specific and schema-complete cache generation. This design transforms genomic surveillance from batch processing to continuous streaming analysis, with cumulative performance benefits as laboratories accumulate alignment data. cgDist functions optimally as a precision "zoom lens" for the detailed investigation of clusters identified through initial cgMLST screening. Rather than restructuring entire population relationships, this targeted approach maximizes epidemiological insight precisely where enhanced resolution is most valuable. The algorithm ensures that cgDist distances are always greater than or equal to corresponding cgMLST distances, preserving epidemiological interpretability while adding critical genetic discrimination. The system includes integrated recombination detection capabilities that leverage cached alignment statistics to identify potential horizontal gene transfer events through mutation density analysis. This multi-scale analytical framework--from population screening through cluster zoom analysis to recombination detection--provides comprehensive surveillance capabilities within the computational constraints of routine public health practice.

bioinformatics↗

bioRxiv2023

A yeast love triangle: multiple hybridizations shape genome evolution in the Pichia cactophila species complex.

Hybrids are chimeric organisms carrying genetic material from at least two divergent parental lineages. Hybridization can contribute to the emergence of novel lineages with unique phenotypic traits that may facilitate their adaptation to new environments. In recent years, genomic analyses have revealed the hybrid nature of several opportunistic human pathogenic yeasts. One of them is Candida inconspicua, a member of the Pichia cactophila species complex, for which all sequenced strains are hybrids isolated from Europe with so far unknown parentals. It has been recently proposed that C. inconspicua and P. cactophila s.s. should be ranked as the same species due to their genetic similarity. To obtain a better understanding of the evolution of this clade, we sequenced the genomes of the P. cactophila type strain, of its close-relative Pichia pseudocactophila, and of a putative C. inconspicua clinical isolate from Alaska and compared them with the previously sequenced genomes of Pichia norvegensis, C. inconspicua and the recently described Pichia galeolata. Our results show evidence for the existence of distinct hybrid lineages within this clade and suggest an intricate scenario of recurrent hybridizations in this species complex, some of them giving rise to lineages with the ability to infect humans. Given their different hybridization histories, we propose that C. inconspicua, P. cactophila, and the new clinical isolate from Alaska should represent three distinct species and suggest the name Pichia alaskaensis for the new taxon. Moreover, the name C. inconspicua is recombined in the genus Pichia as P. inconspicua. Our results clarify the evolutionary relationships within the P. cactophila species complex and underscore the importance of non-vertical evolution.

microbiology↗

bioRxiv2021

Multiple hybridization events punctuate the evolutionary trajectory of Malassezia furfur

Malassezia species are important fungal skin commensals and are part of the normal microbiota of humans and other animals. However, under certain circumstances these fungi can also display a pathogenic behaviour. For example, Malassezia furfur is a common commensal of human skin, and yet is often responsible for skin disorders but also systemic infections. Comparative genomics analysis of M. furfur revealed that some isolates have a hybrid origin, similar to several other recently described hybrid fungal pathogens. Because hybrid species exhibit genomic plasticity that can impact phenotypes, we sought to elucidate the genomic evolution and phenotypic characteristics of M. furfur hybrids in comparison to their parental lineages. To this end, we performed a comparative genomics analysis between hybrid strains and their presumptive parental lineages, and assessed phenotypic characteristics. Our results provide evidence that at least two distinct hybridization events occurred between the same parental lineages, and that the parental strains may have originally been hybrids themselves. Analysis of the mating-type locus reveals that M. furfur has a pseudobipolar mating system, and provides evidence that after sexual liaisons of mating compatible cells, hybridization involved cell-cell fusion leading to a diploid/aneuploid state. This study provides new insights into the evolutionary trajectory of M. furfur and contributes with valuable genomic resources for future pathogenicity studies. ImportanceMalassezia furfur is a common commensal member of human/animal microbiota that is also associated with several pathogenic states. Recent studies report involvement of Malassezia species in Crohns disease, a type of inflammatory bowel disease, pancreatic cancer progression, and exacerbation of Cystic fibrosis. A recent genomics analysis of M. furfur revealed the existence of hybrid isolates and identified their putative parental lineages. In this study, we explored the genomic and phenotypic features of these hybrids in comparison to their putative parental lineages. Our results revealed the existence of a pseudobipolar mating system in this species and showed evidence for the occurrence of multiple hybridization events in the evolutionary trajectory of M. furfur. These findings significantly advance our understanding of the evolution of this commensal microbe and are relevant for future studies exploring the role of hybridization in the adaptation to new niches or environments, including the emergence of pathogenicity.

evolutionary biology↗

bioRxiv2021

Karyon: a computational framework for the diagnosis of hybrids, aneuploids, and other non-standard architectures in genome assemblies.

Recent technological developments have made genome sequencing and assembly accessible to many groups. However, the presence in sequenced organisms of certain genomic features such as high heterozygosity, polyploidy, aneuploidy, or heterokaryosis can challenge current standard assembly procedures and result in highly fragmented assemblies. Hence, we hypothesized that genome databases must contain a non-negligible fraction of low-quality assemblies that result from such type of intrinsic genomic factors. Here we present Karyon, a Python-based toolkit that uses raw sequencing data and de novo genome assembly to assess several parameters and generate informative plots to assist in the identification of non-chanonical genomic traits. Karyon includes automated de novo genome assembly and variant calling pipelines. We tested Karyon by diagnosing 35 highly fragmented publicly available assemblies from 19 different Mucorales (Fungi) species. Our results show that 6 (17%) of the assemblies presented signs of unusual genomic configurations, suggesting that these are common, at least within the Fungi.

genomics↗

bioRxiv2020

Factors enforcing the species boundary between the human pathogens Cryptococcus neoformans and Cryptococcus deneoformans

Hybridization has resulted in the origin and variation in extant species, and hybrids continue to arise despite pre- and post-zygotic barriers that limit their formation and evolutionary success. One important system that maintains species boundaries in prokaryotes and eukaryotes is the mismatch repair pathway, which blocks recombination between divergent DNA sequences. Previous studies illuminated the role of the mismatch repair component Msh2 in blocking genetic recombination between divergent DNA during meiosis. Loss of Msh2 results in increased interspecific genetic recombination in bacterial and yeast models, and increased viability of progeny derived from yeast hybrid crosses. Hybrid isolates of two pathogenic fungal Cryptococcus species, Cryptococcus neoformans and Cryptococcus deneoformans, are isolated regularly from both clinical and environmental sources. In the present study, we sought to determine if loss of Msh2 would relax the species boundary between C. neoformans and C. deneoformans. We found that crosses between these two species in which both parents lack Msh2 produced hybrid progeny with increased viability and high levels of aneuploidy. Whole-genome sequencing revealed few instances of recombination among hybrid progeny and did not identify increased levels of recombination in progeny derived from parents lacking Msh2. Several hybrid progeny produced structures associated with sexual reproduction when incubated alone on nutrient-rich medium in light, a novel phenotype in Cryptococcus. These findings represent a unique, unexpected case where rendering the mismatch repair system defective did not result in increased meiotic recombination across a species boundary. This suggests that alternative pathways or other mismatch repair components limit meiotic recombination between homeologous DNA and enforce species boundaries in the basidiomycete Cryptococcus species. Author summarySeveral mechanisms enforce species boundaries by either preventing the formation of hybrids, known as pre-zygotic barriers, or preventing the viability and fecundity of hybrids, known as post-zygotic barriers. Despite these barriers, interspecific hybrids form at an appreciable frequency, such as hybrid isolates of the human fungal pathogenic species, Cryptococcus neoformans and Cryptococcus deneoformans, which are regularly isolated from both clinical and environmental sources. C. neoformans x C. deneoformans hybrids are typically highly aneuploid, sterile, and display phenotypes intermediate to those of either parent, although self-fertile isolates and transgressive phenotypes have been observed. One important mechanism known to enforce species boundaries or lead to incipient speciation is the DNA mismatch repair system, which blocks recombination between divergent DNA sequences during meiosis. The aim of this study was to determine if genetically deleting the DNA mismatch repair component Msh2 would relax the species boundary between C. neoformans and C. deneoformans. Progeny derived from C. neoformans x C. deneoformans crosses in which both parental strains lacked Msh2 had higher viability, and unlike previous studies in Saccharomyces, these Cryptococcus hybrid progeny had higher levels of aneuploidy and no observable increase in meiotic recombination at the whole-genome level.

genetics↗

bioRxiv2019

Genomic evidence for a hybrid origin of the yeast opportunistic pathogen Candida albicans

Opportunistic yeast pathogens are of increasing medical concern. Candida albicans, the species with the highest incidence, is a natural commensal of humans that can adopt a pathogenic behaviour. This species is highly heterozygous, is an obligate diploid, and cannot undergo meiosis, adopting instead a parasexual cycle. The origin of these traits is unknown and we hypothesize they could result from ancestral hybridization. We tested this idea by analyzing available genomes of C. albicans isolates and comparing them to those of hybrid and non-hybrid strains of other Candida species. Our results show compelling evidence that C. albicans is an evolved hybrid, with levels and patterns of ancestral heterozygosity that cannot be fully explained under the paradigm of vertical evolution. Although the level of inferred divergence between the putative parental lineages (2.8%) is not clearly beyond current species boundaries in Saccharomycotina, we show here that all analyzed C. albicans strains derive from a single hybrid ancestor, which diverged by extensive loss of heterozygosis. This finding has important implications for our understanding of C. albicans evolution, including the loss of the sexual cycle, the origin of the association with humans, and the evolution of virulence traits.

microbiology↗