Minor Mutations Affecting a Metrical Trait
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Weak Selection Revealed by the Whole-Genome Comparison of the X Chromosome and Autosomes of Human and Chimpanzee
Weak selection revealed by the whole-genome comparison of the X chromosome and autosomes of human and chimpanzee Jian Lu and Chung-I Wu* Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637 Communicated by Tomoko Ohta, National Institute of Genetics, Mishima, Japan, January 19, 2005 (received for review November 22, 2004) The effect of weak selection driving genome evolution has at- An alternative approach to measuring the extent and strength tracted much attention in the last decade, but the task of measur- of selection, both positive and negative, is to contrast the ing the strength of such selection is particularly difficult. A useful evolution of X-linked and autosomal genes (18, 19). If the fitness approach is to contrast the evolution of X-linked and autosomal effect of a mutation is (partially) recessive, then this effect can genes in two closely related species in a whole-genome analysis. If be more readily manifested on the X chromosome than on the the fitness effect of mutations is recessive, X-linked genes should autosomes (20). When the recessive mutations are still rare, they evolve more rapidly than autosomal genes when the mutations are will nonetheless be expressed in the hemizygous males of the XY advantageous, and they should evolve more slowly than autoso- system. On the other hand, autosomal mutations have to become mal genes when the mutations are deleterious. We found synon- sufficiently frequent to form homozygotes to be influenced by ymous substitutions on the X chromosome of human and chim- natural selection under random mating. Therefore, if recessive panzee to be less frequent than those on the autosomes. -
Demography and Weak Selection Drive Patterns of Transposable Element Diversity in Natural Populations of Arabidopsis Lyrata
Demography and weak selection drive patterns of transposable element diversity in natural populations of Arabidopsis lyrata Steven Lockton, Jeffrey Ross-Ibarra, and Brandon S. Gaut* Department of Ecology and Evolutionary Biology, University of California, Irvine, CA 92697 Edited by M. T. Clegg, University of California, Irvine, CA, and approved June 25, 2008 (received for review May 13, 2008) Transposable elements (TEs) are the major component of most approximately 6,000 TEs within the A. thaliana genome have been plant genomes, and characterizing their population dynamics is well characterized (4, 19). A. lyrata diverged from A. thaliana Ϸ5 key to understanding plant genome complexity. Yet there have million years ago (20) and has become a model system for plant been few studies of TE population genetics in plant systems. To molecular population genetics (21). A. lyrata is a predominantly study the roles of selection, transposition, and demography in self-incompatible, perennial species distributed across northern and shaping TE population diversity, we generated a polymorphism central Europe, Asia, and North America. A. lyrata consists of large, dataset for six TE families in four populations of the flowering stable populations, particularly in Central Europe where popula- plant Arabidopsis lyrata. The TE data indicated significant differ- tions are hypothesized to have served as Pleistocene refugia (21– entiation among populations, and maximum likelihood procedures 23). Importantly, Ross-Ibarra et al. (24) modeled the demographic suggested weak selection. For strongly bottlenecked populations, history of six natural A. lyrata populations based on single- the observed TE band-frequency spectra fit data simulated under nucleotide polymorphism (SNP) data from 77 nuclear genes. -
DNA Repair and Synthetic Lethality
Int J Oral Sci (2011) 3:176-179. www.ijos.org.cn REVIEW DNA repair and synthetic lethality Gong-she Guo1, Feng-mei Zhang1, Rui-jie Gao2, Robert Delsite4, Zhi-hui Feng1,3*, Simon N. Powell4* 1School of Public Health, Shandong University, Jinan 250012, China; 2Second People’s Hospital of Weifang, Weifang 261041, China; 3Department of Radiation Oncology, Washington University in St Louis, St Louis MO 63108, USA; 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York NY 10065, USA Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells. Keywords: DNA repair; homologous recombination; synthetic lethality; BRCA; Rad52 International Journal of Oral Science (2011) 3: 176-179. doi: 10.4248/IJOS11064 Introduction polymerase (PARP) inhibitors are specifically toxic to homologous recombination (HR)-defective cells [3-4]. Synthetic lethality is defined as a genetic combination Playing a key role in maintaining genetic stability, HR is of mutations in two or more genes that leads to cell a major repair pathway for double-strand breaks (DSBs) death, whereas a mutation in any one of the genes does utilizing undamaged homologous DNA sequence [5-6]. -
A Gain-Of-Function P53-Mutant Oncogene Promotes Cell Fate Plasticity and Myeloid Leukemia Through the Pluripotency Factor FOXH1
Published OnlineFirst May 8, 2019; DOI: 10.1158/2159-8290.CD-18-1391 RESEARCH ARTICLE A Gain-of-Function p53-Mutant Oncogene Promotes Cell Fate Plasticity and Myeloid Leukemia through the Pluripotency Factor FOXH1 Evangelia Loizou1,2, Ana Banito1, Geulah Livshits1, Yu-Jui Ho1, Richard P. Koche3, Francisco J. Sánchez-Rivera1, Allison Mayle1, Chi-Chao Chen1, Savvas Kinalis4, Frederik O. Bagger4,5, Edward R. Kastenhuber1,6, Benjamin H. Durham7, and Scott W. Lowe1,8 Downloaded from cancerdiscovery.aacrjournals.org on September 27, 2021. © 2019 American Association for Cancer Research. Published OnlineFirst May 8, 2019; DOI: 10.1158/2159-8290.CD-18-1391 ABSTRACT Mutations in the TP53 tumor suppressor gene are common in many cancer types, including the acute myeloid leukemia (AML) subtype known as complex karyotype AML (CK-AML). Here, we identify a gain-of-function (GOF) Trp53 mutation that accelerates CK-AML initiation beyond p53 loss and, surprisingly, is required for disease maintenance. The Trp53 R172H muta- tion (TP53 R175H in humans) exhibits a neomorphic function by promoting aberrant self-renewal in leu- kemic cells, a phenotype that is present in hematopoietic stem and progenitor cells (HSPC) even prior to their transformation. We identify FOXH1 as a critical mediator of mutant p53 function that binds to and regulates stem cell–associated genes and transcriptional programs. Our results identify a context where mutant p53 acts as a bona fi de oncogene that contributes to the pathogenesis of CK-AML and suggests a common biological theme for TP53 GOF in cancer. SIGNIFICANCE: Our study demonstrates how a GOF p53 mutant can hijack an embryonic transcrip- tion factor to promote aberrant self-renewal. -
A Role for Genetic Accommodation in Evolution? Christian Braendle1* and Thomas Flatt2
What the papers say A role for genetic accommodation in evolution? Christian Braendle1* and Thomas Flatt2 Summary lowered. Third, selection in the presence of the environmental Whether evolutionary change can occur by genetic factor enriches the previously cryptic alleles determining assimilation, or more generally by genetic accommoda- tion, remains controversial. Here we examine some of the the trait. Eventually, these alleles become so frequent that experimental evidence for both phenomena. Several the expression of the trait overcomes the higher threshold in experiments in Drosophila suggest that assimilation is the absence of the environmental stimulus.(9,20) Thus, genetic (1) possible, and a new paper shows that a color poly- assimilation transforms an environmentally induced (pheno- phenism in the tobacco hornworm, Manduca sexta, can typically plastic) trait into a phenotype which is stably evolve by genetic accommodation. We argue that genetic accommodation, including assimilation, is a plausible expressed without the eliciting environmental stimulus: the mechanism in evolution; however, more work is required genetically assimilated phenotype is no longer plastic, but to test how this mechanism acts and how often it is exhibits a genetically fixed response independent of the involved in evolutionary change. BioEssays 28:868– environmental conditions,(2,9,14,16) a phenomenon called 873, 2006. ß 2006 Wiley Periodicals, Inc. canalization.(20) Genetic assimilation is a special case of a more general Genetic assimilation and accommodation phenomenon, called genetic accommodation, most promi- (2–9) Whether the processes of genetic assimilation and nently proposed by Mary Jane West-Eberhard in 2003.(10) This (1,10) accommodation can explain evolutionary change and scenario of phenotypic evolution posits that (1) a mutation or phenotypic novelty is a controversial issue among evolutionary environmental change triggers the expression of a novel, herit- biologists (for example Refs 11–16). -
Codon Usage Bias in the Model Moss Physcomitrella Patens
GBE Selfing in Haploid Plants and Efficacy of Selection: Codon Usage Bias in the Model Moss Physcomitrella patens Pe´ ter Szo¨ve´nyi,1,* Kristian K. Ullrich,2,7 Stefan A. Rensing,2,3 Daniel Lang,4 Nico van Gessel,5 Hans K. Stenøien,6 Elena Conti,1 and Ralf Reski3,5 1Department of Systematic and Evolutionary Botany, University of Zurich, Switzerland 2Plant Cell Biology, Faculty of Biology, University of Marburg, Germany 3BIOSS—Centre for Biological Signalling Studies, University of Freiburg, Germany 4Plant Genome and Systems Biology, Helmholtz Zentrum Mu¨ nchen, German Research Center for Environmental Health, Neuherberg, Germany 5Plant Biotechnology, Faculty of Biology, University of Freiburg, Germany 6NTNU University Museum, Trondheim, Norway 7Present address: Max-Planck-Insitut fu¨ r Evolutionsbiologie, Plo¨n,Germany *Corresponding author: E-mail: [email protected]. Accepted: May 25, 2017 Data deposition: This project has been deposited at EMBL ENA under the accession PRJEB8683. Abstract A long-term reduction in effective population size will lead to major shift in genome evolution. In particular, when effective population size is small, genetic drift becomes dominant over natural selection. The onset of self-fertilization is one evolutionary event considerably reducing effective size of populations. Theory predicts that this reduction should be more dramatic in organ- isms capable for haploid than for diploid selfing. Although theoretically well-grounded, this assertion received mixed experimen- tal support. Here, we test this hypothesis by analyzing synonymous codon usage bias of genes in the model moss Physcomitrella patens frequently undergoing haploid selfing. In line with population genetic theory, we found that the effect of natural selection on synonymous codon usage bias is very weak. -
Degeneracy and Genetic Assimilation in RNA Evolution Reza Rezazadegan1* and Christian Reidys1,2
Rezazadegan and Reidys BMC Bioinformatics (2018) 19:543 https://doi.org/10.1186/s12859-018-2497-3 RESEARCH ARTICLE Open Access Degeneracy and genetic assimilation in RNA evolution Reza Rezazadegan1* and Christian Reidys1,2 Abstract Background: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations. However adaptive pressure eventually leads to changes in phenotype that involve non-neutral mutations. The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation. We propose quasineutral mutations, i.e. mutations which preserve an element of the phenotype set, as minimal mutations and study their properties. We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences. Results: We show that degenerate sequences i.e. sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation. Degenerate sequences also tend to cluster together in the sequence space. The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e. regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space. We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary. -
Recombination, Dominance and Selection on Amino Acid Polymorphism in the Drosophila Genome: Contrasting Patterns on the X and Fourth Chromosomes
Copyright 2003 by the Genetics Society of America Recombination, Dominance and Selection on Amino Acid Polymorphism in the Drosophila Genome: Contrasting Patterns on the X and Fourth Chromosomes Lea A. Sheldahl, Daniel M. Weinreich and David M. Rand1 Department of Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island 02912 Manuscript received December 14, 2002 Accepted for publication June 27, 2003 ABSTRACT Surveys of nucleotide polymorphism and divergence indicate that the average selection coefficient on Drosophila proteins is weakly positive. Similar surveys in mitochondrial genomes and in the selfing plant Arabidopsis show that weak negative selection has operated. These differences have been attributed to the low recombination environment of mtDNA and Arabidopsis that has hindered adaptive evolution through the interference effects of linkage. We test this hypothesis with new sequence surveys of proteins lying in low recombination regions of the Drosophila genome. We surveyed Ͼ3800 bp across four proteins at the tip of the X chromosome and Ͼ3600 bp across four proteins on the fourth chromosome in 24 strains of D. melanogaster and 5 strains of D. simulans. This design seeks to study the interaction of selection and linkage by comparing silent and replacement variation in semihaploid (X chromosome) and diploid (fourth chromosome) environments lying in regions of low recombination. While the data do indicate very low rates of exchange, all four gametic phases were observed both at the tip of the X and across the ϭ fourth chromosome. Silent variation is very low at the tip of the X ( S 0.0015) and on the fourth ϭ chromosome ( S 0.0002), but the tip of the X shows a greater proportional loss of variation than the fourth shows relative to normal-recombination regions. -
701.Full.Pdf
THE AVERAGE NUMBER OF GENERATIONS UNTIL EXTINCTION OF AN INDIVIDUAL MUTANT GENE IN A FINITE POPULATION MOT00 KIMURA' AND TOMOKO OHTA Department of Biology, Princeton University and National Institute of Genetics, Mishima, Japan Received June 13, 1969 AS pointed out by FISHER(1930), a majority of mutant genes which appear in natural populations are lost by chance within a small number of genera- tions. For example, if the mutant gene is selectively neutral, the probability is about 0.79 that it is lost from the population during the first 7 generations. With one percent selective advantage, this probability becomes about 0.78, namely, it changes very little. In general, the probability of loss in early generations due to random sampling of gametes is very high. The question which naturally follows is how long does it take, on the average, for a single mutant gene to become lost from the population, if we exclude the cases in which it is eventually fixed (established) in the population. In the present paper, we will derive some approximation formulas which are useful to answer this question, based on the theory of KIMURAand OHTA(1969). Also, we will report the results of Monte Carlo experiments performed to check the validity of the approximation formulas. APPROXIMATION FORMULAS BASED ON DIFFUSION MODELS Let us consider a diploid population, and denote by N and Ne, respectively, its actual and effective sizes. The following treatment is based on the diffusion models of population genetics (cf. KIMURA1964). As shown by KIMURAand OHTA (1969), if p is the initial frequency of the mutant gene, the average number of generations until loss of the mutant gene (excluding the cases of its eventual fixation) is - In this formula, 1 On leave from the National Institute of Genetics, Mishima, Japan. -
Extinction Dynamics of Age-Structured Populations in A
Proc. Nadl. Acad. Sci. USA Vol. 85, pp. 7418-7421, October 1988 Population Biology Extinction dynamics of age-structured populations in a fluctuating environment (demography/ecology/life history/stochastic model/diffusion process) RUSSELL LANDE AND STEVEN HECHT ORZACK Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637 Communicated by David M. Raup, June 3, 1988 (received for review February 2, 1988) ABSTRACT We model density-independent growth of an a recursion formula for the numbers of individuals in each age- (or stage-) structured population, assuming that mortality age class or developmental stage at time t + 1 in terms of and reproductive rates fluctuate as stationary time series. An- those at the previous time t, alytical formulas are derived for the distribution of time to extinction and the cumulative probability of extinction before n(t + 1) = A(t)n(t), [1] a certain time, which are determined by the initial age distri- bution, and by the infinitesimal mean and variance, # and a2, where n(t) is a column vector with entries representing the of a diffusion approximation for the logarithm of total popula- numbers of (female) individuals of each type at time t and tion size. These parameters can be estimated from the average A(t) is a square projection matrix with nonnegative entries life history and the pattern of environmental fluctuations in Aij(t) that determine the number of individuals of type i pro- the vital rates. We also show that the distribution of time to duced at time t + 1 per individual of type j at time t. -
Maintenance of Quantitative Genetic Variance Under Partial Self-Fertilization, with Implications for Evolution of Selfing
GENETICS | INVESTIGATION Maintenance of Quantitative Genetic Variance Under Partial Self-Fertilization, with Implications for Evolution of Selfing Russell Lande*,1 and Emmanuelle Porcher† *Department of Life Sciences, Imperial College London, Silwood Park Campus, Ascot, Berkshire SL5 7PY, United Kingdom, and †Centre d’Ecologie et des Sciences de la Conservation (UMR7204), Sorbonne Universités, MNHN, Centre National de la Recherche Scientifique, UPMC, 75005 Paris, France ABSTRACT We analyze two models of the maintenance of quantitative genetic variance in a mixed-mating system of self-fertilization and outcrossing. In both models purely additive genetic variance is maintainedbymutationandrecombinationunder stabilizing selection on the phenotype of one or more quantitative characters. The Gaussian allele model (GAM) involves a finite number of unlinked loci in an infinitely large population, with a normal distribution of allelic effects at each locus within lineages selfed for t consecutive generations since their last outcross. The infinitesimal model for partial selfing (IMS) involves an infinite number of loci in a large but finite population, with a normal distribution of breeding values in lineages of selfing age t. In both models a stable equilibrium genetic variance exists, the outcrossed equilibrium, nearly equal to that under random mating, for all selfing rates, r, up to critical value,^r;the purging threshold, which approximately equals the mean fitness under random mating relative to that under complete selfing. In the GAM a second stable equilibrium, the purged equilibrium, exists for any positive selfing rate, with genetic variance less than or equal to that under pure selfing; as r increases above ^r the outcrossed equilibrium collapses sharply to the purged equilibrium genetic variance. -
A Complete Bibliography of Publications in the Journal of Theoretical Biology: 1990–1999
A Complete Bibliography of Publications in the Journal of Theoretical Biology: 1990{1999 Nelson H. F. Beebe University of Utah Department of Mathematics, 110 LCB 155 S 1400 E RM 233 Salt Lake City, UT 84112-0090 USA Tel: +1 801 581 5254 FAX: +1 801 581 4148 E-mail: [email protected], [email protected], [email protected] (Internet) WWW URL: http://www.math.utah.edu/~beebe/ 01 June 2019 Version 1.00 Title word cross-reference 2 [SOR91]. 3 [LBND98, Mar92b, SL91a, Van91]. 4 [Lac90]. 6 [RP99]. > [Hir93]. + [BS92, Cla95, Joh93, NK90]. 2+ [AH90, Cha90, CJMBM92, HP97a, ◦ KD94, Kum91, LF95, LC97, LH91, LR94c, SW91]. [Fli99]. 0 [O'N91]. 1 [O'N91]. 2 [CLY99]. 3 [KD94, LR94c, WBC99]. cmax [WBC99]. i [LR94c]. ml + [WBC99]. α [LBDDG90, MGL 95, Nak95, SST91, TSC90]. b1 [Yar96]. β [Iid90, Rad91, TSC90]. · [SST91, Spe90]. ∆ [Fri98]. [Boe90]. g [MNB97]. Km [RP96]. L = C [Hes90]. µ [RSB92]. N [Dug90, Bla97]. p [DGSK99, Khr98]. Φ [N¨ol98, N¨ol99]. ΦF (0) [PN98]. ! [MR98, O'N91]. -1 [LBND98]. -Adic [DGSK99, Khr98]. -amylase-catalyzed [Nak95]. -ATPase [BS92]. -azaadenine [SOR91]. -chymotrypsin [LBDDG90]. -D [Mar92b, SL91a, Van91]. -dependent [MNB97, CJMBM92]. -globin [Boe90, Iid90]. -helix [TSC90]. -induced [KD94]. -morphogen [Lac90]. -person [Dug90]. -phosphogluconolactone [RP99]. -player [Bla97]. -sarcin [MGL+95]. -sarcin-membrane [MGL+95]. -structure [TSC90]. 1 2 -structures [Rad91]. -thalassemia [Iid90]. -values [N¨ol98, N¨ol99]. [Boe90]. /K [BS92]. 1 [Fin92b, Ham93, Mel93a, TCZ95, TL98, WDP98]. 1-dimenthylurea [LBND98]. 100 [CF94b]. 100-A˚ [CF94b]. 16S [AIK99]. 185 [BBM+13a, BBM+13b]. 19th [Ano99c]. 2 [MK93, SST91]. 2- [RSB92]. 2nd [Ano99a]. 353-379 [Ano92-29].