Biology subjects

Escalera-Zamudio, M.

Publications and source records attributed to Escalera-Zamudio, M..

5 recordsLinked to original sources

bioRxiv2024

Intrahost dynamics, together with genetic and phenotypic effects predict the success of viral mutations

Predicting the fitness of mutations in the evolution of pathogens is a long-standing and important, yet largely unsolved problem. In this study, we used SARS-CoV-2 as a model system to explore whether the intrahost diversity of viral infections could provide clues on the relative fitness of single amino acid variants (SAVs). To do so, we analysed [~]15 million complete genomes and nearly [~]8000 sequencing libraries generated from SARS-CoV-2 infections, which were collected at various timepoints during the COVID-19 pandemic. Across timepoints, we found that many of the SAVs that went on to reach high frequency could be detected in the intrahost diversity of samples collected at a median of 3-22 months prior. Additionally, we found that genetic linkage patterns observed at the interhost level can also be observed in the intrahost diversity of infections. Application of machine learning models allowed us to learn highly generalisable intrahost, physiochemical and phenotypic patterns to forecast the future fitness of intrahost SAVs (r2=0.48-0.63). Most of these models performed significantly better when considering genetic linkage between mutations (r2=0.53-0.67), pointing to epistasis being an important determinant in the evolution of SARS-CoV-2. Overall, our results highlight the predictive power of intrahost diversity data, and document the evolutionary forces shaping the fitness of mutations. Such insights offer potential to forecast the emergence of future variants and ultimately inform the design of vaccine targets.

genomics↗

bioRxiv2022

Comparing the evolutionary dynamics of predominant SARS-CoV-2 virus lineages co-circulating in Mexico

Over 200 different SARS-CoV-2 lineages have been observed in Mexico by November 2021. To investigate lineage replacement dynamics, we applied a phylodynamic approach and explored the evolutionary trajectories of five dominant lineages that circulated during the first year of local transmission. For most lineages, peaks in sampling frequencies coincided with different epidemiological waves of infection in Mexico. Lineages B.1.1.222 and B.1.1.519 exhibited similar dynamics, constituting clades that likely originated in Mexico and persisted for >12 months. Lineages B.1.1.7, P.1 and B.1.617.2 also displayed similar dynamics, characterized by multiple introduction events leading to a few successful extended local transmission chains that persisted for several months. For the largest B.1.617.2 clades, we further explored viral lineage movements across Mexico. Many clades were located within the south region of the country, suggesting that this area played a key role in the spread of SARS-CoV-2 in Mexico.

evolutionary biology↗

bioRxiv2021

Identification of site-specific evolutionary trajectories shared across human betacoronaviruses

Comparing the evolution of distantly related viruses can provide insights into common adaptive processes related to shared ecological niches. Phylogenetic approaches, coupled with other molecular evolution tools, can help identify mutations informative on adaptation, whilst the structural contextualization of these to functional sites of proteins may help gain insight into their biological properties. Two zoonotic betacoronaviruses capable of sustained human-to-human transmission have caused pandemics in recent times (SARS-CoV-1 and SARS-CoV-2), whilst a third virus (MERS-CoV) is responsible for sporadic outbreaks linked to animal infections. Moreover, two other betacoronaviruses have circulated endemically in humans for decades (HKU1 and OC43). To search for evidence of adaptive convergence between established and emerging betacoronaviruses capable of sustained human-to-human transmission (HKU1, OC43, SARS-CoV-1 and SARS-CoV-2), we developed a methodological pipeline to classify shared non-synonymous mutations as putatively denoting homoplasy (repeated mutations that do not share direct common ancestry) or stepwise evolution (sequential mutations leading towards a novel genotype). In parallel, we look for evidence of positive selection, and draw upon protein structure data to identify potential biological implications. We find 30 mutations, with four of these [codon sites 18121 (nsp14/residue 28), 21623 (spike/21), 21635 (spike/25) and 23948 (spike/796); SARS-CoV-2 genome numbering] displaying evolution under positive selection and proximity to functional protein regions. Our findings shed light on potential mechanisms underlying betacoronavirus adaptation to the human host and pinpoint common mutational pathways that may occur during establishment of human endemicity.

evolutionary biology↗

bioRxiv2020

Genomic analysis of early SARS-CoV-2 strains introduced in Mexico

The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described in the country. Within this Mexican cluster, we also identified an H49Y amino acid change in the spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts. This work is the result of the collaboration of five institutions into one research consortium: three public health institutes and two universities. From the beginning of this work, it was agreed that the experimental leader of each institution would share the first authorship. Those were the criteria followed to assign first co-first authorship in this manuscript. The order of the other authors was randomly assigned. IMPORTANCEUnderstanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.

genomics↗

bioRxiv2018

Parallel Evolution and the Emergence of Highly Pathogenic Avian Influenza A Viruses

Parallel molecular evolution and adaptation are important phenomena commonly observed in viruses. Here we exploit parallel molecular evolution to understand virulence evolution in avian influenza viruses (AIV). Highly-pathogenic AIVs independently evolve from low-pathogenic ancestors via acquisition of a polybasic cleavage sites (pCS). Why some AIV lineages but not others evolve in this way is unknown. We hypothesise that the parallel emergence of highly-pathogenic AIV may be facilitated by permissive or compensatory mutations occurring across the AIV genome. We combined phylogenetic, statistical and structural approaches to discover parallel mutations in AIV genomes associated with the highly-pathogenic phenotype. Parallel mutations were screened using a new statistical test of mutation-phenotype association and further evaluated in the contexts of positive selection and protein function. The mutational panel we present reveals new links between virulence evolution and other viral traits and raises the possibility of predicting aspects of AIV evolution.

evolutionary biology↗