Search results for "epistasis"
showing 10 items of 37 documents
Temperature-dependent mutational robustness can explain faster molecular evolution at warm temperatures, affecting speciation rate and global pattern…
2015
Distribution of species across the Earth shows strong latitudinal and altitudinal gradients with the number of species decreasing with declining temperatures. While these patterns have been recognized for well over a century, the mechanisms generating and maintaining them have remained elusive. Here, we propose a mechanistic explanation for temperature-dependent rates of molecular evolution that can influence speciation rates and global biodiversity gradients. Our hypothesis is based on the effects of temperature and temperature-adaptation on stability of proteins and other catalytic biomolecules. First, due to the nature of physical forces between biomolecules and water, stability of biomo…
The roles of whole-genome and small-scale duplications in the functional specialization of Saccharomyces cerevisiae genes
2013
Researchers have long been enthralled with the idea that gene duplication can generate novel functions, crediting this process with great evolutionary importance. Empirical data shows that whole-genome duplications (WGDs) are more likely to be retained than small-scale duplications (SSDs), though their relative contribution to the functional fate of duplicates remains unexplored. Using the map of genetic interactions and the re-sequencing of 27 Saccharomyces cerevisiae genomes evolving for 2,200 generations we show that SSD-duplicates lead to neo-functionalization while WGD-duplicates partition ancestral functions. This conclusion is supported by: (a) SSD-duplicates establish more genetic i…
A Network Model for the Correlation between Epistasis and Genomic Complexity
2008
The study of genetic interactions (epistasis) is central to the understanding of genome organization and evolution. A general correlation between epistasis and genomic complexity has been recently shown, such that in simpler genomes epistasis is antagonistic on average (mutational effects tend to cancel each other out), whereas a transition towards synergistic epistasis occurs in more complex genomes (mutational effects strengthen each other). Here, we use a simple network model to identify basic features explaining this correlation. We show that, in small networks with multifunctional nodes, lack of redundancy, and absence of alternative pathways, epistasis is antagonistic on average. In c…
Effect of gene-gene and gene-environment interactions associated with antituberculosis drug-induced hepatotoxicity.
2017
This study evaluated the association between environmental factors and genetic variations in enzymes that metabolize antituberculosis (anti-TB) drugs [arylamine N-acetyltransferase 2, cytochrome P450 2E1 (CYP2E1), glutathione S-transferase theta 1 (GSTT1), and glutathione S-transferase mu 1] with antituberculosis drug-induced hepatotoxicity (ATDH). We also investigated the potential gene-gene and gene-environment interactions as well as their association with ATDH development in a population of hospitalized TB patients from Buenos Aires.We investigated 364 TB patients who received anti-TB drugs. Physicians collected demographic and clinical data to identify environmental risk factors for AT…
Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function
2016
Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarke…
Increased RNA virus population diversity improves adaptability
2021
The replication machinery of most RNA viruses lacks proofreading mechanisms. As a result, RNA virus populations harbor a large amount of genetic diversity that confers them the ability to rapidly adapt to changes in their environment. In this work, we investigate whether further increasing the initial population diversity of a model RNA virus can improve adaptation to a single selection pressure, thermal inactivation. For this, we experimentally increased the diversity of coxsackievirus B3 (CVB3) populations across the capsid region. We then compared the ability of these high diversity CVB3 populations to achieve resistance to thermal inactivation relative to standard CVB3 populations in an…
A generalization of Kingman's model of selection and mutation and the Lenski experiment.
2017
Kingman’s model of selection and mutation studies the limit type value distribution in an asexual population of discrete generations and infinite size undergoing selection and mutation. This paper generalizes the model to analyze the long-term evolution of Escherichia. coli in Lenski experiment. Weak assumptions for fitness functions are proposed and the mutation mechanism is the same as in Kingman’s model. General macroscopic epistasis are designable through fitness functions. Convergence to the unique limit type distribution is obtained.
Ultra-Fast Detection of Higher-Order Epistatic Interactions on GPUs
2017
Detecting higher-order epistatic interactions in Genome-Wide Association Studies (GWAS) remains a challenging task in the fields of genetic epidemiology and computer science. A number of algorithms have recently been proposed for epistasis discovery. However, they suffer from a high computational cost since statistical measures have to be evaluated for each possible combination of markers. Hence, many algorithms use additional filtering stages discarding potentially non-interacting markers in order to reduce the overall number of combinations to be examined. Among others, Mutual Information Clustering (MIC) is a common pre-processing filter for grouping markers into partitions using K-Means…
Testing the Domino Theory of Gene Loss in Buchnera aphidicola: The Relevance of Epistatic Interactions
2018
The domino theory of gene loss states that when some particular gene loses its function and cripples a cellular function, selection will relax in all functionally related genes, which may allow for the non-functionalization and loss of these genes. Here we study the role of epistasis in determining the pattern of gene losses in a set of genes participating in cell envelope biogenesis in the endosymbiotic bacteria Buchnera aphidicola. We provide statistical evidence indicating pairs of genes in B. aphidicola showing correlated gene loss tend to have orthologs in Escherichia coli known to have alleviating epistasis. In contrast, pairs of genes in B. aphidicola not showing correlated gene loss…
DLG5 variants do not influence susceptibility to inflammatory bowel disease in the Scottish population
2005
Introduction: Recent data have suggested that specific haplotypic variants of the DLG5 gene on chromosome 10q23 may be associated with susceptibility to inflammatory bowel disease (IBD) in Germany. Haplotype D, notably characterised by the presence of a G→A substitution at nucleotide 113, was associated with susceptibility to Crohn’s disease (CD) whereas an extended haplotype A conferred protection. Aims: Association of DLG5 haplotypic variants with disease susceptibility, genotype-phenotype relationships, and epistasis with CARD15 was investigated in the Scottish population. Patients and methods: A total of 374 CD, 305 ulcerative colitis (UC), and 294 healthy controls (HC) were studied. Ge…