Critical Mutation Rate has an Exponential Dependence on Population Size for Eukaryotic-length Genomes with Crossover

The critical mutation rate (CMR) determines the shift between survival-of-the-fittest and survival of individuals with greater mutational robustness (“flattest”). We identify an inverse relationship between CMR and sequence length in an in silico system with a two-peak fitness landscape; CMR decreases to no more than five orders of magnitude above estimates of eukaryotic per base mutation rate. We confirm the CMR reduces exponentially at low population sizes, irrespective of peak radius and distance, and increases with the number of genetic crossovers. We also identify an inverse relationship between CMR and the number of genes, confirming that, for a similar number of genes to that for the plant Arabidopsis thaliana (25,000), the CMR is close to its known wild-type mutation rate; mutation rates for additional organisms were also found to be within one order of magnitude of the CMR. This is the first time such a simulation model has been assigned input and produced output within range for a given biological organism. The decrease in CMR with population size previously observed is maintained; there is potential for the model to influence understanding of populations undergoing bottleneck, stress, and conservation strategy for populations near extinction.

[1]  C. Pál,et al.  Metabolic network analysis of the causes and evolution of enzyme dispensability in yeast , 2004, Nature.

[2]  I. Chelo,et al.  Evolution of Outcrossing in Experimental Populations of Caenorhabditis elegans , 2012, PloS one.

[3]  M. Nowak Evolutionary Dynamics: Exploring the Equations of Life , 2006 .

[4]  D. Bartel,et al.  Long noncoding RNAs in C. elegans , 2012, Genome research.

[5]  Meredith V. Trotter,et al.  Robustness and evolvability. , 2010, Trends in genetics : TIG.

[6]  M. Huynen,et al.  Neutral evolution of mutational robustness. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  M. Lynch Rate, molecular spectrum, and consequences of human mutation , 2010, Proceedings of the National Academy of Sciences.

[8]  R. Lande Genetics and demography in biological conservation. , 1988, Science.

[9]  M. Nowak,et al.  Viral quasi-species and recombination , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[10]  Manolis Kellis,et al.  Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions , 2012, Science.

[11]  C. Simon,et al.  Evolutionary ecology of periodical insects. , 1994, Trends in ecology & evolution.

[12]  E. Domingo,et al.  The 30th anniversary of quasispecies , 2009, EMBO reports.

[13]  Roman V. Belavkin,et al.  Critical mutation rate in a population with horizontal gene transfer , 2017, ECAL.

[14]  D. Krakauer,et al.  Redundancy, antiredundancy, and the robustness of genomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Profile of Michael Lynch , 2010, Proceedings of the National Academy of Sciences.

[16]  H. A. Orr,et al.  The population genetics of beneficial mutations , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[17]  M. P. Cummings,et al.  Nucleotide sequence diversity at the alcohol dehydrogenase 1 locus in wild barley (Hordeum vulgare ssp. spontaneum): an evaluation of the background selection hypothesis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  M. Eigen,et al.  What is a quasispecies? , 2006, Current topics in microbiology and immunology.

[19]  M. Nachman,et al.  Estimate of the mutation rate per nucleotide in humans. , 2000, Genetics.

[20]  H. Mori,et al.  Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection , 2006, Molecular systems biology.

[21]  C. Wilke,et al.  Evolution of mutational robustness. , 2003, Mutation research.

[22]  B. De Baets,et al.  Genome analysis of the smallest free-living eukaryote Ostreococcus tauri unveils many unique features. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[23]  P. Phillips Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems , 2008, Nature Reviews Genetics.

[24]  D. Halligan,et al.  Estimation of the Spontaneous Mutation Rate per Nucleotide Site in a Drosophila melanogaster Full-Sib Family , 2013, Genetics.

[25]  Claus O. Wilke,et al.  Adaptive evolution on neutral networks , 2001, Bulletin of mathematical biology.

[26]  T. Jukes,et al.  The neutral theory of molecular evolution. , 2000, Genetics.

[27]  Roman V. Belavkin,et al.  Critical Mutation Rate has an Exponential Dependence on Population Size for Eukaryotic-Length Genomes , 2016, ALIFE.

[28]  Michael Lachmann,et al.  Quasispecies Made Simple , 2005, PLoS Comput. Biol..

[29]  Claus O Wilke,et al.  Quasispecies theory in the context of population genetics , 2005, BMC Evolutionary Biology.

[30]  Vineet K. Sharma,et al.  (TG/CA)n repeats in human gene families: abundance and selective patterns of distribution according to function and gene length , 2005, BMC Genomics.

[31]  Vikas Rai Role of Space , 2013 .

[32]  Thomas G. Doak,et al.  Drift-barrier hypothesis and mutation-rate evolution , 2012, Proceedings of the National Academy of Sciences.

[33]  O. Martin,et al.  Genome-Wide Crossover Distribution in Arabidopsis thaliana Meiosis Reveals Sex-Specific Patterns along Chromosomes , 2011, PLoS genetics.

[34]  Erich Bornberg-Bauer,et al.  Robustness versus evolvability: A paradigm revisited , 2010, HFSP journal.

[35]  Inman Harvey,et al.  Recombination and Error Thresholds in Finite Populations , 1998, FOGA.

[37]  M. Lynch Evolution of the mutation rate. , 2010, Trends in genetics : TIG.

[38]  M. Kimura,et al.  The mutational load with epistatic gene interactions in fitness. , 1966, Genetics.

[39]  A. W. F. Edwards,et al.  The statistical processes of evolutionary theory , 1963 .

[40]  R. Solé,et al.  Simple quasispecies models for the survival-of-the-flattest effect: The role of space. , 2008, Journal of theoretical biology.

[41]  F. Montero,et al.  The relationship between the error catastrophe, survival of the flattest, and natural selection , 2011, BMC Evolutionary Biology.

[42]  The Arabidopsis Genome Initiative Analysis of the genome sequence of the flowering plant Arabidopsis thaliana , 2000, Nature.

[43]  Huanming Yang,et al.  Human Y Chromosome Base-Substitution Mutation Rate Measured by Direct Sequencing in a Deep-Rooting Pedigree , 2009, Current Biology.

[44]  Karsten M. Borgwardt,et al.  Whole-genome sequencing of multiple Arabidopsis thaliana populations , 2011, Nature Genetics.

[45]  Data production leads,et al.  An integrated encyclopedia of DNA elements in the human genome , 2012 .

[46]  R. B. Azevedo,et al.  On the Immortality of Television Sets: “Function” in the Human Genome According to the Evolution-Free Gospel of ENCODE , 2013, Genome biology and evolution.

[47]  J. Drake,et al.  Rates of spontaneous mutation. , 1998, Genetics.

[48]  Claus O. Wilke,et al.  SELECTION FOR FITNESS VERSUS SELECTION FOR ROBUSTNESS IN RNA SECONDARY STRUCTURE FOLDING , 2001, Evolution; international journal of organic evolution.

[49]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[50]  P. Sniegowski,et al.  Mutation Rates: How Low Can You Go? , 2013, Current Biology.

[51]  F. Welch,et al.  Causes and Consequences , 2017, Nature.

[52]  R. Tarchini,et al.  A Single Amino Acid Difference Distinguishes Resistant and Susceptible Alleles of the Rice Blast Resistance Gene Pi-ta , 2000, Plant Cell.

[53]  E. Koonin,et al.  Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. , 2002, Genome research.

[54]  Circadian clocks of faster developing fruit fly populations also age faster , 2014, Biogerontology.

[55]  Sudhir Kumar,et al.  Mutation rates in mammalian genomes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[56]  A. Channon,et al.  Critical Mutation Rate Has an Exponential Dependence on Population Size in Haploid and Diploid Populations , 2013, PloS one.

[57]  Alpan Raval,et al.  Evolution favors protein mutational robustness in sufficiently large populations , 2007 .

[58]  Michael Lynch,et al.  Direct Estimation of the Mitochondrial DNA Mutation Rate in Drosophila melanogaster , 2008, PLoS biology.

[59]  D. Hartl,et al.  Principles of population genetics , 1981 .

[60]  M. Sachs,et al.  Two Alleles of Maize ALCOHOL DEHYDROGENASE 1 Have 3' Structural and Poly(a) Addition Polymorphisms. , 1986, Genetics.

[61]  W. J. Dickinson,et al.  A genome-wide view of the spectrum of spontaneous mutations in yeast , 2008, Proceedings of the National Academy of Sciences.

[62]  Michael Ashburner,et al.  Drosophila melanogaster: a case study of a model genomic sequence and its consequences. , 2005, Genome research.

[63]  D. Altshuler,et al.  A map of human genome variation from population-scale sequencing , 2010, Nature.

[64]  M. Bevan,et al.  The Arabidopsis genome: a foundation for plant research. , 2005, Genome research.

[65]  Ó. Crosbie,et al.  Hepatitis C quasispecies adaptation in the setting of a variable fidelity polymerase , 2012 .

[66]  James C. Frauenthal,et al.  Stable Points, Stable Cycles and Chaos , 1979 .

[67]  Richard M. Clark,et al.  The Rate and Molecular Spectrum of Spontaneous Mutations in Arabidopsis thaliana , 2010, Science.

[68]  Marian Thomson,et al.  Analysis of the genome sequences of three Drosophila melanogaster spontaneous mutation accumulation lines. , 2009, Genome research.

[69]  Inman Harvey,et al.  Optimal Mutation Rates and Selection Pressure in Genetic Algorithms , 2000, GECCO.

[70]  M. Nowak,et al.  Error thresholds of replication in finite populations mutation frequencies and the onset of Muller's ratchet. , 1989, Journal of theoretical biology.

[71]  Gabriela Ochoa,et al.  Error Thresholds in Genetic Algorithms , 2006, Evolutionary Computation.

[72]  M. Eigen,et al.  The Hypercycle , 2004, Naturwissenschaften.

[73]  L. Kvist,et al.  Low population viability in small endangered orchid populations: Genetic variation, seedling recruitment and stochasticity , 2017 .

[74]  Dee R. Denver,et al.  High mutation rate and predominance of insertions in the Caenorhabditis elegans nuclear genome , 2004, Nature.

[75]  Xiaowei Wu,et al.  Branching Processes with Biological Applications , 2010 .

[76]  C. Wilke SELECTION FOR FITNESS VERSUS SELECTION FOR ROBUSTNESS IN RNA SECONDARY STRUCTURE FOLDING , 2001, Evolution; international journal of organic evolution.

[77]  N. Ellstrand,et al.  POPULATION GENETIC CONSEQUENCES OF SMALL POPULATION SIZE: Implications for Plant Conservation , 1993 .

[78]  Terence Soule,et al.  Comparing genetic robustness in generational vs. steady state evolutionary algorithms , 2006, GECCO.

[79]  Jeffrey E. Barrick,et al.  Balancing Robustness and Evolvability , 2006, PLoS biology.

[80]  Andrés Moya,et al.  Validating viral quasispecies with digital organisms: a re-examination of the critical mutation rate , 2005, BMC Evolutionary Biology.

[81]  Kei-Hoi Cheung,et al.  A Statistical Framework to Predict Functional Non-Coding Regions in the Human Genome Through Integrated Analysis of Annotation Data , 2015, Scientific Reports.

[82]  Raymond K. Auerbach,et al.  An Integrated Encyclopedia of DNA Elements in the Human Genome , 2012, Nature.

[83]  M. Miyamoto,et al.  Mutation rate variation in multicellular eukaryotes: causes and consequences , 2007, Nature Reviews Genetics.

[84]  P. Hogeweg,et al.  Error-threshold exists in fitness landscapes with lethal mutants , 2007, BMC Evolutionary Biology.

[85]  R M May,et al.  Biological Populations with Nonoverlapping Generations: Stable Points, Stable Cycles, and Chaos , 1974, Science.

[86]  C. Ofria,et al.  Evolution of digital organisms at high mutation rates leads to survival of the flattest , 2001, Nature.

[87]  Emmanuel Tannenbaum,et al.  Solution of the quasispecies model for an arbitrary gene network. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[88]  M. Cargill Characterization of single-nucleotide polymorphisms in coding regions of human genes , 1999, Nature Genetics.