Biology subjects

Mateus, D.

Publications and source records attributed to Mateus, D..

4 recordsLinked to original sources

bioRxiv2026

SACHET: seeded contour tracking measures Rab conversion kinetics on individual endosomes in live cells

Membrane-labeled endosomes appear as hollow rings in a projection; they move, deform and exchange their coat, which population trackers (tools that detect every object of one kind and link the detections across frames) are not designed to follow. Here we introduce SACHET (Seeded Adaptive Contour & Hollow Endosome Tracking), a human-supervised Fiji tool that tracks one endosome at a time. On simulated ground truth it localizes the center to 10 nm, recovers transition time constants and lags without bias and holds the target among touching neighbors; comparisons with tuned TrackMate and Cellpose delineate where each is superior. In crowded spinning-disk projections, TrackMate followed one of seven marked Rab5-to-Rab7 conversions; supervised SACHET followed all 37. SACHET thus provides a stable per-endosome frame in which membrane morphology and protein exchange can be quantified: in five cell lines the conversion toggles like a digital switch within seconds to minutes, differing between lines.

cell biology↗

bioRxiv2020

De novo formation of an early endosome during Rab5 to Rab7 transition

Rab5 and Rab7a are the main determinants of early and late endosomes and are important regulators of endosomal progression. The transport from early endosomes to late endosome seems to be regulated through an endosomal maturation switch where Rab5 is exchanged with Rab7a on the same endosome. Here we provide new insight into the mechanism of endosomal maturation where we have discovered a stepwise Rab5 detachment, sequentially regulated by Rab7a. The initial detachment of Rab5 is Rab7a independent and demonstrate a diffusion-like exchange between cytosol and endosomal membrane, and the second phase is slower where Rab5 converges into a specific domain that specifically detaches as a Rab5 indigenous endosome. Consequently, we show that early endosomal maturation regulated through the Rab5 to Rab7a switch induce the formation of a new fully functional early endosome. Progression through a stepwise early endosomal maturation regulates the direction of the transport and concomitantly regulates the homeostasis of early endosomes.View Full Text

cell biology↗

bioRxiv2019

Ecological divergence and hybridization of Neotropical Leishmania parasites

The tropical Andes is an important natural laboratory to understand speciation and diversification in many taxa. Here, we examined the evolutionary history of parasites of the Leishmania braziliensis species complex based on whole genome sequencing of 67 isolates from 47 localities in Peru. We firstly show the origin of near-clonal Andean Leishmania lineages that diverged from admixed Amazonian ancestors, accompanied by a significant reduction in genome diversity and large structural variations implicated in host-parasite interactions. Beside a clear dichotomy between Andean and Amazonian species, patterns of population structure were strongly associated with biogeographical origin. Molecular clock analyses and ecological niche modeling suggested that the history of diversification of the Andean lineages is limited to the Late Pleistocene and intimately associated with habitat contractions driven by climate change. These results support a wider model on trypanosomatid evolution where major parasite lineages emerge through ecological fitting. Second, genome-scale analyses provided evidence of meiotic recombination between Andean and Amazonian Leishmania species, resulting in full-genome hybrids. The mitochondrial genome of these hybrids consisted of homogeneous uniparental maxicircles, but minicircles originated from both parental species, leaving a mosaic ancestry of minicircle-encoded guide RNA genes. We further show that mitochondrial minicircles - but not maxicircles - show a similar evolutionary pattern as the nuclear genome, suggesting that biparental inheritance of minicircles is universal and may be important to alleviate maxicircle-nuclear incompatibilities. By comparing full nuclear and mitochondrial genome ancestries, our data expands our appreciation on the genetic consequences of diversification and hybridization in parasitic protozoa.

genomics↗

bioRxiv2019

Genomic analysis of natural intra-specific hybrids among Ethiopian isolates of Leishmania donovani

Parasites of the genus Leishmania (Kinetoplastida: Trypanosomatidae) cause widespread and devastating human diseases, ranging from self-healing but disfiguring cutaneous lesions to destructive mucocutaneous presentations or usually fatal visceral disease. Visceral leishmaniasis due to Leishmania donovani is endemic in Ethiopia where it has also been responsible for major epidemics. The presence of hybrid genotypes has been widely reported in surveys of natural populations, genetic variation reported in a number of Leishmania species, and the extant capacity for genetic exchange demonstrated in laboratory experiments. However, patterns of recombination and evolutionary history of admixture that produced these hybrid populations remain unclear, as most of the relevant literature examines only a limited number (typically fewer than 10) genetic loci. Here, we use whole-genome sequence data to investigate Ethiopian L. donovani isolates previously characterised as hybrids by microsatellite and multi-locus sequencing. To date there is only one previous study on a natural population of Leishmania hybrids, based on whole-genome sequence. The current findings demonstrate important differences. We propose hybrids originate from recombination between two different lineages of Ethiopian L. donovani occurring in the same region. Patterns of inheritance are more complex than previously reported with multiple, apparently independent, origins from similar parents that include backcrossing with parental types. Analysis indicates that hybrids are representative of at least three different histories. Furthermore, isolates were highly polysomic at the level of chromosomes with startling differences between parasites recovered from a recrudescent infection from a previously treated individual. The results demonstrate that recombination is a significant feature of natural populations and contributes to the growing body of evidence describing how recombination, and gene flow, shape natural populations of Leishmania.\n\nAuthor SummaryLeishmaniasis is a spectrum of diseases caused by the protozoan parasite Leishmania. It is transmitted by sandfly insect vectors and is responsible for an enormous burden of human suffering. In this manuscript we examine Leishmania isolates from Ethiopia that cause the most serious form of the disease, namely visceral leishmaniasis, which is usually fatal without treatment. Historically the general view was that such parasites reproduce clonally, so that their progeny are genetically identical to the founding cells. This view has changed over time and it is increasingly clear that recombination between genetically different Leishmania parasites occurs. The implication is that new biological traits such as virulence, resistance to drug treatments or the ability to infect new species of sandfly could emerge. The frequency and underlying mechanism of such recombination in natural isolates is poorly understood. Here we perform a detailed whole genome analysis on a cohort of hybrid isolates from Ethiopia together with their potential parents to assess the genetic nature of hybrids in more detail. Results reveal a complex pattern of mating and inbreeding indicative of multiple mating events that has likely shaped the epidemiology of the disease agent. We also show that some hybrids have very different relative amounts of DNA (polysomy) the implications of which are discussed. Together the results contribute to a fuller understanding of the nature of genetic recombination in natural populations of Leishmania.

genomics↗