scholarly journals Varying Patterns of Mutation: Measuring the Universality of Regional Mutation Rates

Elements ◽  
2008 ◽  
Vol 4 (1) ◽  
Author(s):  
Aleah Fox
Keyword(s):  
Genetic Variation ◽  
Mutation Rates ◽  
Rate Distribution ◽  
Coding Regions ◽  
Uniform Rate ◽  
Sexual Recombination ◽  
Ultimate Source

Mutations are the ultimate source of genetic variation in DNA. The patterns of mutation, however, can vary both within and across genomes. It has previously been shown that several mammals have heterogeneous mutation rates, while four yeasts have been observed to have uniform rates. The generality of these observations has not been known. Here we examine silen tsite substitutions in coding regions of 20 mammals, 27 yeast, and 4 insects, to determine which genomes demonstrate this mosaic rate distribution and which are uniform. Our findings show that mutational heterogeneity occurs in all branches of the mammalian phylogeny, as well as in flies and mosquitoes. All yeasts have a uniform rate across their genomes with the exception of three <em>candida</em> species: <em>c. albicans</em>, <em>c. dubliniensis</em>, and <em>c. tropicalis</em>. We hypothesize that this is due to the lack of sexual recombination in these species, leading to the regional accumulation of mutations.

scholarly journals Evolution of mutation rates in hypermutable populations of Escherichia coli propagated at very small effective population size

2017 ◽  
Vol 13 (3) ◽  
pp. 20160849 ◽  
Author(s):  
Tanya Singh ◽  
Meredith Hyun ◽  
Paul Sniegowski
Keyword(s):  
Escherichia Coli ◽  
Genetic Variation ◽  
Mutation Rate ◽  
Mutation Rates ◽  
Deleterious Mutations ◽  
Effective Population ◽  
Ultimate Source ◽  
Systematic Evolution ◽  
Small Effective Size ◽  
Small Effective Population Size

Mutation is the ultimate source of the genetic variation—including variation for mutation rate itself—that fuels evolution. Natural selection can raise or lower the genomic mutation rate of a population by changing the frequencies of mutation rate modifier alleles associated with beneficial and deleterious mutations. Existing theory and observations suggest that where selection is minimized, rapid systematic evolution of mutation rate either up or down is unlikely. Here, we report systematic evolution of higher and lower mutation rates in replicate hypermutable Escherichia coli populations experimentally propagated at very small effective size—a circumstance under which selection is greatly reduced. Several populations went extinct during this experiment, and these populations tended to evolve elevated mutation rates. In contrast, populations that survived to the end of the experiment tended to evolve decreased mutation rates. We discuss the relevance of our results to current ideas about the evolution, maintenance and consequences of high mutation rates.

scholarly journals The Genome of the Human Pathogen Candida albicans is Shaped by Mutation and Cryptic Sexual Recombination

2018 ◽  
Author(s):  
Joshua M. Wang ◽  
Richard J. Bennett ◽  
Matthew Z. Anderson
Keyword(s):  
Candida Albicans ◽  
Loss Of Heterozygosity ◽  
Diploid Species ◽  
Clinical Isolates ◽  
Base Substitution ◽  
Mitochondrial Genomes ◽  
Genetic Changes ◽  
Coding Regions ◽  
Sexual Recombination ◽  
Species Evolution

ABSTRACTThe opportunistic fungal pathogen Candida albicans lacks a conventional sexual program and is thought to evolve, at least primarily, through the clonal acquisition of genetic changes. Here, we performed an analysis of heterozygous diploid genomes from 21 clinical isolates to determine the natural evolutionary processes acting on the C. albicans genome. Consistent with a model of inheritance by descent, most single nucleotide polymorphisms (SNPs) were shared between closely related strains. However, strain-specific SNPs and insertions/deletions (indels) were distributed non-randomly across the genome. For example, base substitution rates were higher in the immediate vicinity of indels, and heterozygous regions of the genome contained significantly more strain-specific polymorphisms than homozygous regions. Loss of heterozygosity (LOH) events also contributed substantially to genotypic variation, with most long-tract LOH events extending to the ends of the chromosomes suggestive of repair via break-induced replication. Importantly, some isolates contained highly mosaic genomes and failed to cluster closely with other isolates within their assigned clades. Mosaicism is consistent with strains having experienced inter-clade recombination during their evolutionary history and a detailed examination of nuclear and mitochondrial genomes revealed striking examples of recombination. Together, our analyses reveal that both (para)sexual recombination and mitotic mutational processes drive evolution of this important pathogen in nature. To further facilitate the study of genome differences we also introduce an online platform, SNPMap, to examine SNP patterns in sequenced C. albicans genomes.AUTHOR SUMMARYMutations introduce variation into the genome upon which selection can act. Defining the nature of these changes is critical for determining species evolution, as well as for understanding the genetic changes driving important cellular processes such as carcinogenesis. The fungus Candida albicans is a heterozygous diploid species that is both a frequent commensal organism and a prevalent opportunistic pathogen. Prevailing theory is that C. albicans evolves primarily through the gradual build-up of mutations, and a pressing question is whether sexual or parasexual processes also operate within natural populations. Here, we determine the evolutionary patterns of genetic change that have accompanied species evolution in nature by examining genomic differences between clinical isolates. We establish that the C. albicans genome evolves by a combination of base-substitution mutations, insertions/deletion events, and both short-tract and long-tract loss of heterozygosity (LOH) events. These mutations are unevenly distributed across the genome, and reveal that non-coding regions and heterozygous regions are evolving more quickly than coding regions and homozygous regions, respectively. Furthermore, we provide evidence that genetic exchange has occurred between isolates, establishing that sexual or parasexual processes have transpired in C. albicans populations and contribute to the diversity of both nuclear and mitochondrial genomes.

scholarly journals Evidence for Transcriptome-wide RNA Editing Among Sus scrofa PRE-1 SINE Elements

2017 ◽  
Author(s):  
Scott A. Funkhouser ◽  
Juan P. Steibel ◽  
Ronald O. Bates ◽  
Nancy E. Raney ◽  
Darius Schenk ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Transcriptional Regulation ◽  
Rna Editing ◽  
High Throughput ◽  
Sus Scrofa ◽  
Sequence Data ◽  
Rna Sequences ◽  
Editing Event ◽  
Coding Regions ◽  
Dna And Rna

AbstractBackgroundRNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.ResultsHere, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.ConclusionsThus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.

scholarly journals De novo mutations across 1,465 diverse genomes reveal novel mutational insights and reductions in the Amish founder population

2019 ◽  
Author(s):  
Michael D. Kessler ◽  
Douglas P. Loesch ◽  
James A. Perry ◽  
Nancy L. Heard-Costa ◽  
Brian E. Cade ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Mutation Rate ◽  
De Novo ◽  
Population Level ◽  
Mutation Rates ◽  
Founder Population ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Nucleotide Mutation ◽  
Rare Genetic Variation

Abstractde novo Mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) program, we directly estimate and analyze DNM counts, rates, and spectra from 1,465 trios across an array of diverse human populations. Using the resulting call set of 86,865 single nucleotide DNMs, we find a significant positive correlation between local recombination rate and local DNM rate, which together can explain up to 35.5% of the genome-wide variation in population level rare genetic variation from 41K unrelated TOPMed samples. While genome-wide heterozygosity does correlate weakly with DNM count, we do not find significant differences in DNM rate between individuals of European, African, and Latino ancestry, nor across ancestrally distinct segments within admixed individuals. However, interestingly, we do find significantly fewer DNMs in Amish individuals compared with other Europeans, even after accounting for parental age and sequencing center. Specifically, we find significant reductions in the number of T→C mutations in the Amish, which seems to underpin their overall reduction in DNMs. Finally, we calculate near-zero estimates of narrow sense heritability (h2), which suggest that variation in DNM rate is significantly shaped by non-additive genetic effects and/or the environment, and that a less mutagenic environment may be responsible for the reduced DNM rate in the Amish.SignificanceHere we provide one of the largest and most diverse human de novo mutation (DNM) call sets to date, and use it to quantify the genome-wide relationship between local mutation rate and population-level rare genetic variation. While we demonstrate that the human single nucleotide mutation rate is similar across numerous human ancestries and populations, we also discover a reduced mutation rate in the Amish founder population, which shows that mutation rates can shift rapidly. Finally, we find that variation in mutation rates is not heritable, which suggests that the environment may influence mutation rates more significantly than previously realized.

scholarly journals Evolutionary and functional lessons from human-specific amino acid substitution matrices

2021 ◽  
Vol 3 (3) ◽  
Author(s):  
Tair Shauli ◽  
Nadav Brandes ◽  
Michal Linial
Keyword(s):  
Genetic Variation ◽  
Amino Acid ◽  
Human Genetic Variation ◽  
Post Translational Modification ◽  
Functional Protein ◽  
Homologous Proteins ◽  
Specific Amino Acid ◽  
Coding Regions ◽  
Substitution Matrices ◽  
Human Specific

Abstract Human genetic variation in coding regions is fundamental to the study of protein structure and function. Most methods for interpreting missense variants consider substitution measures derived from homologous proteins across different species. In this study, we introduce human-specific amino acid (AA) substitution matrices that are based on genetic variations in the modern human population. We analyzed the frequencies of &gt;4.8M single nucleotide variants (SNVs) at codon and AA resolution and compiled human-centric substitution matrices that are fundamentally different from classic cross-species matrices (e.g. BLOSUM, PAM). Our matrices are asymmetric, with some AA replacements showing significant directional preference. Moreover, these AA matrices are only partly predicted by nucleotide substitution rates. We further test the utility of our matrices in exposing functional signals of experimentally-validated protein annotations. A significant reduction in AA transition frequencies was observed across nine post-translational modification (PTM) types and four ion-binding sites. Our results propose a purifying selection signal in the human proteome across a diverse set of functional protein annotations and provide an empirical baseline for interpreting human genetic variation in coding regions.

scholarly journals Genetic variation of populations of Citrus psorosis virus

2006 ◽  
Vol 87 (10) ◽  
pp. 3097-3102 ◽  
Author(s):  
Susana Martín ◽  
María Laura García ◽  
Antonella Troisi ◽  
Luis Rubio ◽  
Gonzalo Legarreta ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Type Species ◽  
Protein Gene ◽  
Nucleotide Substitutions ◽  
Coding Regions ◽  
Citrus Psorosis Virus ◽  
Selection For ◽  
Genomic Regions ◽  
Two Populations ◽  
Amino Acid Sequence Conservation

Citrus psorosis virus (CPsV), the type species of genus Ophiovirus, has a segmented, negative-stranded RNA genome. We examined the population structure and genetic variation of CPsV in three coding regions located in RNAs 1, 2 and 3, analysing 22 isolates from Argentina, California, Florida, Italy and Spain. Most isolates contained a predominant sequence and some minor variants. Estimations of the genetic diversity and phylogenetic clustering of isolates disclosed two populations, one comprising isolates from Spain, Italy, Florida and California and the other including the Argentinean isolates. Isolate CPV-4 (from Texas) included for comparison was distant from both groups, suggesting that it belongs to a third group. The low ratio between non-synonymous and synonymous nucleotide substitutions indicated strong selection for amino acid sequence conservation, particularly in the coat protein gene. Incongruent phylogenetic relationships in different genomic regions suggested that exchange of genomic segments may have contributed to CPsV evolution.

scholarly journals Mutations and quantitative genetic variation: lessons from Drosophila

2010 ◽  
Vol 365 (1544) ◽  
pp. 1229-1239 ◽  
Author(s):  
Trudy F. C. Mackay
Keyword(s):  
Genetic Variation ◽  
Quantitative Traits ◽  
Genetic Correlations ◽  
Intermediate Frequency ◽  
Mutation Rates ◽  
Stabilizing Selection ◽  
Detailed Knowledge ◽  
Multiple Traits ◽  
Association Analyses ◽  
Specific Effects

A central issue in evolutionary quantitative genetics is to understand how genetic variation for quantitative traits is maintained in natural populations. Estimates of genetic variation and of genetic correlations and pleiotropy among multiple traits, inbreeding depression, mutation rates for fitness and quantitative traits and of the strength and nature of selection are all required to evaluate theoretical models of the maintenance of genetic variation. Studies in Drosophila melanogaster have shown that a substantial fraction of segregating variation for fitness-related traits in Drosophila is due to rare deleterious alleles maintained by mutation–selection balance, with a smaller but significant fraction attributable to intermediate frequency alleles maintained by alleles with antagonistic pleiotropic effects, and late-age-specific effects. However, the nature of segregating variation for traits under stabilizing selection is less clear and requires more detailed knowledge of the loci, mutation rates, allelic effects and frequencies of molecular polymorphisms affecting variation in suites of pleiotropically connected traits. Recent studies in D. melanogaster have revealed unexpectedly complex genetic architectures of many quantitative traits, with large numbers of pleiotropic genes and alleles with sex-, environment- and genetic background-specific effects. Future genome wide association analyses of many quantitative traits on a common panel of fully sequenced Drosophila strains will provide much needed empirical data on the molecular genetic basis of quantitative traits.

scholarly journals Temperature-dependence of spontaneous mutation rates

2020 ◽  
Author(s):  
Ann-Marie Waldvogel ◽  
Markus Pfenninger
Keyword(s):  
Genetic Variation ◽  
Null Hypothesis ◽  
Spontaneous Mutation ◽  
Empirical Support ◽  
Mutation Rates ◽  
Temperature Extremes ◽  
Whole Genome ◽  
Direct Impact ◽  
Species Specific ◽  
Dependent Processes

Mutation is the source of genetic variation and the fundament of evolution. At the interphase of ecology and evolution, temperature has long been suggested to have a direct impact on realised spontaneous mutation rates. The question is whether mutation rates can be a species-specific constant under variable environmental conditions, such as variation of the ambient temperature. By combining mutation accumulation with whole genome sequencing in a multicellular organism, we provide empirical support to reject this null hypothesis. Instead mutation rates depend on temperature in a U-shaped manner with increasing rates towards both temperature extremes. This relation has important implications for mutation dependent processes in molecular evolution, processes shaping the evolution of mutation rates and even the evolution of biodiversity as such.

scholarly journals Genetic variation in heat tolerance of the coral Platygyra daedalea offers the potential for adaptation to ocean warming

2020 ◽  
Author(s):  
Holland Elder ◽  
Virginia Weis ◽  
Jose Montalvo-Proano ◽  
Veronique J.L Mocellin ◽  
Andrew H. Baird ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Heat Stress ◽  
Heat Tolerance ◽  
Nucleotide Polymorphisms ◽  
Narrow Sense Heritability ◽  
Coding Regions ◽  
Genomic Tools ◽  
Coral Reef Ecosystems ◽  
Few Data ◽  
Genomic Regions

AbstractReef-building corals are foundational species in coral reef ecosystems and are threatened by many stressors including rising ocean temperatures. In 2015/16 and 2016/17, corals around the world experienced consecutive bleaching events and most coral populations are projected to experience temperatures above their current bleaching thresholds annually by 2050. Adaptation to higher temperatures is therefore necessary if corals are to persist in a warming future. While many aspects of heat stress have been well studied, few data are available for predicting the capacity for adaptive cross-generational responses in corals. To address this knowledge gap, we quantified the heritability and genetic variation associated with heat tolerance in Platygyra daedalea from the Great Barrier Reef (GBR). We tracked the survival of replicate quantitative genetic crosses (or families) of coral larvae from six parents in a heat stress selection experiment. We also identified allelic shifts in heat-selected survivors versus paired, non-selected controls of the same coral crosses. We estimated narrow sense heritability to be 0.66 and detected a total of 1,069 single nucleotide polymorphisms (SNPs) associated with heat tolerance. An overlap of 148 unique SNPs shared between experimental crosses indicates that specific genomic regions are responsible for heat tolerance of P. daedalea and some of these SNPs fall in coding regions. These findings suggest that this P. daedalea population has the genetic prerequisites for adaptation to increasing temperatures. This study also provides knowledge for the development of high throughput genomic tools to screen for variation within and across populations to harness or enhance adaptation through assisted gene flow and assisted migration.

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