Miguel Arenas

University of Vigo | UVIGO · Department of Biochemistry, Genetics and Immunology

Probabilistic phylogenetic tree reconstruction is traditionally performed under a best-fitting substitution model of molecular evolution previously selected according to diverse statistical criteria. Interestingly, some recent studies proposed that this procedure is unnecessary for phylogenetic tree reconstruction leading to a debate in the field....

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) produced diverse molecular variants during its recent expansion in humans that caused different transmissibility and severity of the associated disease as well as resistance to monoclonal antibodies and polyclonal sera, among other treatments. In order to understand the causes and con...

The current knowledge about how protein structures influence sequence evolution is rarely incorporated into substitution models adopted for phylogenetic inference, which are commonly based on independent with the same substitution process and ignore the known variation of the evolutionary rates across sites with different structural properties. In...

Type IB topoisomerases relax the torsional stress associated with DNA metabolism in the nucleus and mitochondria and constitute important molecular targets of anticancer drugs. Vertebrates stand out among eukaryotes by having two Type IB topoisomerases acting specifically in the nucleus (TOP1) and mitochondria (TOP1MT). Despite their major importan...

The evolution of structural proteins is generally constrained by the folding stability. However, little is known about the particular capacity of viral proteins to accommodate mutations that can potentially affect the protein stability and, in general, the evolution of the protein stability over time. As an illustrative model case, here we investig...

Genetic recombination is a common evolutionary mechanism that produces molecular diversity. However, its consequences on protein folding stability have not attracted the same attention as in the case of point mutations. Here, we studied the effects of homologous recombination on the computationally predicted protein folding stability for several pr...

Background Long-Term Non-Progressors (LTNPs) are untreated Human Immunodeficiency virus type 1 (HIV-1) infected individuals able to control disease progression for prolonged periods. However, the LTNPs status is temporary, as viral load increases followed by decreases in CD4 + T-cell counts. Control of HIV-1 infection in LTNPs viremic controllers,...

The reconstruction of genetic material of ancestral organisms constitutes a powerful application of evolutionary biology. A fundamental step in this inference is the ancestral sequence reconstruction (ASR), which can be performed with diverse methodologies implemented in computer frameworks. However, most of these methodologies ignore evolutionary...

The selection of the best-fitting substitution model of molecular evolution is a traditional step for phylogenetic inferences, including ancestral sequence reconstruction (ASR). However, a few recent studies suggested that applying this procedure does not affect the accuracy of phylogenetic tree reconstruction. Here, we revisited this debate topic...

TOPIIA topoisomerases are required for the regulation of DNA topology by DNA cleavage and re-ligation and are important targets of antibiotic and anticancer agents. Humans possess two TOPIIA paralogue genes (TOP2A and TOP2B) with high sequence and structural similarity but distinct cellular functions. Despite their functional and clinical relevance...

Spatial turnover of biological communities is determined by both dispersal and environmental constraints. However, we lack quantitative predictions about how these factors interact and influence turnover across genealogical scales. In this study, we have implemented a predictive framework based on approximate Bayesian computation (ABC) to quantify...

The last glacial period (LGP) promoted a loss of genetic diversity in Paleolithic populations of modern humans from diverse regions of the world by range contractions and habitat fragmentation. However, this period also provided some currently submersed lands, such as the Sunda shelf in Southeast Asia (SEA), that could have favored the expansion of...

Diverse phylogenetic methods require a substitution model of evolution that should mimic, as accurately as possible, the real substitution process. At the protein level, empirical substitution models have traditionally been based on a large number of different proteins from particular taxonomic levels. However, these models assume that all of the p...

Motivation The evolutionary processes of mutation and recombination, upon which selection operates, are fundamental to understand the observed molecular diversity. Unlike nucleotide sequences, the estimation of the recombination rate in protein sequences has been little explored, neither implemented in evolutionary frameworks, despite protein seque...

The COVID‐19 pandemic is promoting online education. In this concern, not only online teaching of wet laboratory practices is being challenging, but also online teaching of practices in bioinformatics. Here, I discuss the problematic of online teaching practices in bioinformatics and provide fundamental guidelines, especially oriented for beginner...

DNA topoisomerase III beta (TOP3B) is unique by operating on both DNA and RNA substrates to regulate gene expression and genomic stability. Mutations in human TOP3B are linked to neurodevelopmental and cognitive disorders, highlighting its relevance for human health. Despite the emerging importance of TOP3B, its precise cellular functions and evolu...

Recombination between the X and Y human sex chromosomes is limited to the two pseudoautosomal regions (PARs) that present quite distinct evolutionary origins. Despite the crucial importance for male meiosis, genetic diversity patterns and evolutionary dynamics of these regions are poorly understood. In the present study, we analyzed and compared th...

The history of modern humans in the Iberian Peninsula includes a variety of population arrivals sometimes presenting admixture with resident populations. Genetic data from current Iberian populations revealed an overall east - west genetic gradient that some authors interpreted as a direct consequence of the Reconquista, where Catholic Kingdoms exp...

Background: Dementia due to Alzheimer's disease (AD) is a complex neurodegenerative disorder, which much of heritability remains unexplained. At the clinical level, one of the most common physiological alterations is the slowing of oscillatory brain activity, measurable by electroencephalography (EEG). Relative power (RP) at the conventional frequ...

The evolution of protein-coding genes is usually driven by selective processes, which favor some evolutionary trajectories over others, optimizing the subsequent protein stability and activity. The analysis of selection in this type of genetic data is broadly performed with the metric nonsynonymous/synonymous substitution rate ratio (dN/dS). Howeve...

Brain waves, measured by electroencephalography (EEG), are a powerful tool in the investigation of neurophysiological traits and a noninvasive and cost-effective alternative in the diagnostic of some neurological diseases. In order to identify novel Quantitative Trait Loci (QTLs) for brain wave relative power (RP), we collected resting state EEG da...

Pulmonary Arterial Hypertension (PAH) is a rare and fatal disease where knowledge about its genetic basis continues to increase. In this study, we used targeted panel sequencing in a cohort of 624 adult and pediatric patients from the Spanish PAH registry. We identified 11 rare variants in the ATP‑binding Cassette subfamily C member 8 (ABCC8) gene,...

Proteins are commonly used as molecular targets against pathogens such as viruses and bacteria. However, pathogens can evolve rapidly permitting their populations to increase in protein diversity over time and thus escape to the activity of a molecular therapy. Subsequently, in order to design more durable and robust therapies as well as to underst...

Cavalli‐Sforza and coauthors originally explored the genetic variation of modern humans throughout the world and observed an overall east‐west genetic gradient in Asia. However, the specific environmental and population genetics processes causing this gradient were not formally investigated and promoted discussion in recent studies. Here we studied...

Despite the efforts made to reconstruct the history of modern humans, there are still poorly explored regions that are key for understanding the phylogeography of our species. One of them is the Philippines, which is crucial to unravel the colonization of Southeast Asia and Oceania but where little is known about when and how the first humans arriv...

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease associated with cognitive decline. It is one of the most severe brain disorders affecting the elderly population, being secondary to the increase of life expectancy. Although multi-factorial, the primarily genetic risk factor for late-onset AD is the Apolipoprotein E (APOE) e4 alle...

The development of High-Throughput Sequencing (HTS) technologies is having a major impact on the genomic analysis of viral populations. Current HTS platforms can capture nucleic acid variation across millions of genes for both selected amplicons and full viral genomes. HTS has already facilitated the discovery of new viruses, hinted new taxonomic c...

Recombination drives evolution in diverse viruses by creating new genetic variants upon which selection operates. These recombinant variants can exhibit resistance to drug therapies, increase viral fitness and favor the emergence of epidemic outbreaks, among others. In addition, recombination influences evolutionary analyses based on phylogenetic t...

1. The ancestral sequence reconstruction (ASR) is a molecular evolution technique that provides applications to a variety of fields such as biotechnology and biomedicine. In order to infer ancestral sequences with realistic biological properties, the accuracy of ASR methods is crucial. We previously developed an ASR framework for proteins, called P...

Alzheimer’s disease is a progressive neurodegenerative disease associated with cognitive decline. It is one of the most severe brain disorders and a widened public heath issue due to the increase of life expectancy. It is estimated that by 2030 around 74.7 million people worldwide may be affected with the pathology. Although multifactorial, the pri...

Alzheimer’s disease is a progressive neurodegenerative disease associated with cognitive decline. It is one of the most severe brain disorders and a widened public heath issue due to the increase of life expectancy. It is estimated that by 2030 around 74.7 million people worldwide may be affected with the pathology. Although multifactorial, the pri...

The aim of this project is the development of a bioinformatics tool to aid in the diagnosis of Alzheimer's disease, allowing an early detection and a better characterization of its different stages. This tool will combine genetic data and brain activity. The tool will base its accuracy on the correlation between the genetic information and the elec...

The location of the high mountains of southern Europe has been crucial in the phylogeography of most European species, but how extrinsic (topography of sky islands) and intrinsic features (dispersal dynamics) have interacted to shape the genetic structure in alpine restricted species is still poorly known. Here we investigated the mechanisms explai...

Motivation: The nonsynonymous/synonymous substitution rate ratio (dN/dS) is a commonly used parameter to quantify molecular adaptation in protein-coding data. It is known that the estimation of dN/dS can be biased if some evolutionary processes are ignored. In this concern, common ML methods to estimate dN/dS assume invariable codon frequencies am...

The Iberian Peninsula is a well-delimited geographic region with a rich and complex human history. However, the causes of its genetic structure and past migratory dynamics are not yet fully understood. In order to shed light on them, here we evaluated the gene flow and genetic structure throughout the Iberian Peninsula with spatially explicit model...

SPLATCHE3 simulates genetic data under a variety of spatially explicit evolutionary scenarios, extending previous versions of the framework. The new capabilities include long-distance migration, spatially and temporally heterogeneous short-scale migrations, alternative hybridization models, simulation of serial samples of genetic data and a large v...

The molecular clock hypothesis, which states that substitutions accumulate in protein sequences at a constant rate, plays a fundamental role in molecular evolution but it is violated when selective or mutational processes vary with time. Such violations of the molecular clock have been widely investigated for protein sequences, but not yet for prot...

Phylogenetic inference from protein data is traditionally based on empirical substitution models of evolution that assume that protein sites evolve independently of each other and under the same substitution process. However, it is well known that the structural properties of a protein site in the native state affect its evolution, in particular th...

Selecting among alternative scenarios of human evolution is nowadays a common methodology to investigate the history of our species. This strategy is usually based on computer simulations of genetic data under different evolutionary scenarios, followed by a fitting of the simulated data with the real data. A recent trend in the investigation of anc...

The number of amino acids that occupy a given protein site during evolution reflects the selective constraints operating on the site. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, whil...

Source codes of the program Prot_Evol The source code (in C programming language) can be compiled and run as explained in the README file included in the package.

Site-specific substitution rate versus sequence entropy for all sites of nine randomly chosen proteins. The selection model is WT, the mutation model is based on the empirical flux Each point represents the substitution rate versus the sequence entropy for all sites of the protein with PDB code indicated in the plot. One can spot two branches, corr...

Site-specific substitution rate versus sequence entropy for all sites of nine randomly chosen proteins. The selection model is MF, the mutation model is based on the empirical flux Each point represents the substitution rate versus the sequence entropy for all sites of the protein with PDB code indicated in the plot. One can spot two branches, corr...

Site-specific substitution rate versus sequence entropy for all sites of 9 proteins. The selection model is MF, the mutation model is codon-based, with parameters optimized for each protein separately Each point represents the substitution rate versus the sequence entropy for all sites of the protein with PDB code indicated in the plot. White circl...

Site-specific substitution rate versus sequence entropy for all sites of 9 proteins. The selection model is WT, the mutation model is codon-based, with parameters separately optimized for each protein Each point represents the substitution rate versus the sequence entropy for all sites of the protein with PDB code indicated in the plot. White circl...

European genetic gradients of modern humans were initially interpreted as a consequence of the demic diffusion of expanding Neolithic farmers. However, recent studies showed that these gradients may also be influenced by other evolutionary processes such as population admixture or range contractions. Genetic gradients were observed in the Americas,...

Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, whi...

Protein sites present different amino acids during their evolution, whose number reflects the selective constraints operating on them. This evolutionary variability is strongly influenced by the structural properties of the site in the native structure, and it is quantified either through sequence entropy or through substitution rates. However, whi...

Since 1998 multilocus sequence typing (MLST) has been widely used for molecular characterization of bacteria and fungi because of its molecular and technical advantages. MLST data are highly variable and informative, universally comparable, easily validated, accessible through the Internet, and transferable across researchers. MLST data are current...

Protein structures strongly influence molecular evolution. In particular, the evolutionary rate of a protein site depends on the number of its native contacts. Stability constrained models of protein evolution consider this influence of protein structure on evolution by predicting the effect of mutations on the stability of the native state, but th...

Significance and impact of the study: The knowledge on the composition of the phyllosphere microbial community is still limited, especially when fungi are concerned. These micro-organisms not only play a crucial role in crop health and productivity but also interact with the winemaking process, determining the safety and quality of grape and grape...

The spotted catshark (Scyliorhinus canicula) and the blackmouth catshark (Galeus melastomus) are demersal sharks showing a distinct bathymetric distribution in the western Mediterranean. Together, both species represent more than 85% of the total abundance of demersal chondrichthyans in this Mediterranean basin. Our study provides a complete analys...

During the Neolithic, human populations underwent cultural and technological developments that led to an agricultural revolution. Although the population genetics and evolution of European Neolithic populations have been extensively studied, little is known regarding the Neolithic expansion in North Africa with respect to Europe. One could expect t...

While traditional forensic genetics has been oriented towards using human DNA in criminal investigation and civil court cases, it currently presents a much wider application range, including not only legal situations sensu stricto but also and, increasingly often, to preemptively avoid judicial processes. Despite some difficulties, current forensic...

Illustrative examples of scenarios of nonhuman genetic material (NHGM) for main evidence in litigations not related with human identification. (PDF)

Illustrative examples of scenarios using nonhuman genetic material (NHGM) for auxiliary evidence in litigations related with human identification. (PDF)

Literature cited in the supplementary material. (PDF)

Next-generation sequencing (NGS), also known as high-throughput sequencing, is changing the field of microbial genomics research. NGS allows for a more comprehensive analysis of the diversity, structure and composition of microbial genes and genomes compared to the traditional automated Sanger capillary sequencing at a lower cost. NGS strategies ha...

Mutation and recombination drive the evolution of most pathogens by generating the genetic variants upon which selection operates. Those variants can, for example, confer resistance to host immune systems and drug therapies or lead to epidemic outbreaks. Given their importance, diverse evolutionary studies have investigated the abundance and conseq...

The rapid evolution of Hepatitis B virus (HBV) through both evolutionary forces, mutation and recombination, allows this virus to generate a large variety of adapted variants at both intra and inter-host levels. It can, for instance, generate drug resistance or the diverse viral genotypes that currently exist in the HBV epidemics. Concerning the la...

The computational reconstruction of ancestral proteins provides information on past biological events and has practical implications for biomedicine and biotechnology. Currently available tools for ancestral sequence reconstruction (ASR) are often based on empirical amino acid substitution models that assume that all sites evolve at the same rate a...

This chapter describes the influences of diverse evolutionary phenomena on phylogenetic tree reconstruction and provides strategies to consider such phenomena. Three main approaches are currently applied to reconstruct phylogenetic trees, namely, distance-based methods (Neighbor-Joining (NJ)), maximum likelihood (ML) methods, and Bayesian methods....

Most previous attempts at reconstructing the past history of human populations did not explicitly take geography into account or considered very simple scenarios of migration and ignored environmental information. However, it is likely that the last glacial maximum (LGM) affected the demography and the range of many species, including our own. More...

Substitution models of evolution describe the process of genetic variation through fixed mutations and constitute the basis of the evolutionary analysis at the molecular level. Almost 40 years after the development of first substitution models, highly sophisticated, and data-specific substitution models continue emerging with the aim of better mimi...

RNA viruses exist as complex mixtures of genotypes, known as quasispecies, where the evolution potential resides in the whole community of related genotypes. Quasispecies structure and dynamics have been studied in detail for virus infecting animals and plants but remain unexplored for those infecting microorganisms in environmental samples. We rep...

A variety of enzyme inhibitors have been developed in combating HIV-1, however the fast evolutionary rate of this virus commonly leads to the emergence of resistance mutations that finally allows the mutant virus to survive. This review explores the main genetic consequences of HIV-1 molecular evolution during antiviral therapies, including the vir...

Figure S1. Nucleotide diversity variation. Figure S2. Histogram on the distribution of the significant nonsynonymous substitutions (95% CI), induced by the studied PIs, along the PR coding gene. Table S1. Estimates of overall mean distance with MEGA. Table S2. Estimates of nucleotide genetic diversity. Table S3. Estimates of molecular adaptation wi...

Despite intense work, incorporating constraints on protein native structures into the mathematical models of molecular evolution remains difficult, since most models and programs assume that protein sites evolve independently whereas protein stability is maintained by interactions between sites. Here we address this problem by developing a new mean...

NGS technologies present a fast and cheap generation of genomic data. Nevertheless, ancestral genome inference is not so straightforward due to complex evolutionary processes acting on this material such as inversions, translocations, and other genome rearrangements that, in addition to their implicit complexity, can co-occur and confound ancestral...