Are Synonymous Sites in Primates and Rodents Functionally Constrained?
Tóm tắt
It has been claimed that synonymous sites in mammals are under selective constraint. Furthermore, in many studies the selective constraint at such sites in primates was claimed to be more stringent than that in rodents. Given the larger effective population sizes in rodents than in primates, the theoretical expectation is that selection in rodents would be more effective than that in primates. To resolve this contradiction between expectations and observations, we used processed pseudogenes as a model for strict neutral evolution, and estimated selective constraint on synonymous sites using the rate of substitution at pseudosynonymous and pseudononsynonymous sites in pseudogenes as the neutral expectation. After controlling for the effects of GC content, our results were similar to those from previous studies, i.e., synonymous sites in primates exhibited evidence for higher selective constraint that those in rodents. Specifically, our results indicated that in primates up to 24 % of synonymous sites could be under purifying selection, while in rodents synonymous sites evolved neutrally. To further control for shifts in GC content, we estimated selective constraint at fourfold degenerate sites using a maximum parsimony approach. This allowed us to estimate selective constraint using mutational patterns that cause a shift in GC content (GT ↔ TG, CT ↔ TC, GA ↔ AG, and CA ↔ AC) and ones that do not (AT ↔ TA and CG ↔ GC). Using this approach, we found that synonymous sites evolve neutrally in both primates and rodents. Apparent deviations from neutrality were caused by a higher rate of C → A and C → T mutations in pseudogenes. Such differences are most likely caused by the shift in GC content experienced by pseudogenes. We conclude that previous estimates according to which 20–40 % of synonymous sites in primates were under selective constraint were most likely artifacts of the biased pattern of mutation.
Tài liệu tham khảo
Akashi H, Eyre-Walker A (1998) Translational selection and molecular evolution. Curr Opin Genet Dev 8:688
Arndt PF, Petrov DA, Hwa T (2003) Distinct changes of genomic biases in nucleotide substitution at the time of Mammalian radiation. Mol Biol Evol 20:1887
Berglund J, Pollard KS, Webster MT (2009) Hotspots of biased nucleotide substitutions in human genes. PLoS Biol 7:e26
Bielawski JP, Dunn KA, Yang Z (2000) Rates of nucleotide substitution and mammalian nuclear gene evolution. Approximate and maximum-likelihood methods lead to different conclusions. Genetics 156:1299
Bustamante CD, Nielsen R, Hartl DL (2002) A maximum likelihood method for analyzing pseudogene evolution: implications for silent site evolution in humans and rodents. Mol Biol Evol 19:110
Caceres EF, Hurst LD (2013) The evolution, impact and properties of exonic splice enhancers. Genome Biol 14:R143
Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, Trembath RC (2004) A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet 13:2361
Chamary JV, Parmley JL, Hurst LD (2006) Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet 7:98
Charlesworth B (2009) Fundamental concepts in genetics: effective population size and patterns of molecular evolution and variation. Nat Rev Genet 10:195
Chen CL, Rappailles A, Duquenne L, Huvet M, Guilbaud G, Farinelli L, Audit B, d’Aubenton-Carafa Y, Arneodo A, Hyrien O, Thermes C (2010) Impact of replication timing on non-CpG and CpG substitution rates in mammalian genomes. Genome Res 20:447
Comeron JM (2006) Weak selection and recent mutational changes influence polymorphic synonymous mutations in humans. Proc Natl Acad Sci USA 103:6940
Coulondre C, Miller JH, Farabaugh PJ, Gilbert W (1978) Molecular basis of base substitution hotspots in Escherichia coli. Nature 274:775
Doherty A, McInerney JO (2013) Translational selection frequently overcomes genetic drift in shaping synonymous codon usage patterns in vertebrates. Mol Biol Evol 30:2263
dos Reis M, Savva R, Wernisch L (2004) Solving the riddle of codon usage preferences: a test for translational selection. Nucleic Acids Res 32:5036
Drummond DA, Wilke CO (2008) Mistranslation-induced protein misfolding as a dominant constraint on coding-sequence evolution. Cell 134:341
Duan J, Wainwright MS, Comeron JM, Saitou N, Sanders AR, Gelernter J, Gejman PV (2003) Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor. Hum Mol Genet 12:205
Duret L (2002) Evolution of synonymous codon usage in metazoans. Curr Opin Genet Dev 12:640
Duret L, Arndt PF (2008) The impact of recombination on nucleotide substitutions in the human genome. PLoS Genet 4:e1000071
Eory L, Halligan DL, Keightley PD (2010) Distributions of selectively constrained sites and deleterious mutation rates in the hominid and murid genomes. Mol Biol Evol 27:177
Fairbrother WG, Holste D, Burge CB, Sharp PA (2004) Single nucleotide polymorphism-based validation of exonic splicing enhancers. PLoS Biol 2:E268
Flicek P, Ahmed I, Amode MR, Barrell D, Beal K, Brent S, Carvalho-Silva D, Clapham P, Coates G, Fairley S, Fitzgerald S, Gil L, Garcia-Giron C, Gordon L, Hourlier T, Hunt S, Juettemann T, Kahari AK, Keenan S, Komorowska M, Kulesha E, Longden I, Maurel T, McLaren WM, Muffato M, Nag R, Overduin B, Pignatelli M, Pritchard B, Pritchard E, Riat HS, Ritchie GR, Ruffier M, Schuster M, Sheppard D, Sobral D, Taylor K, Thormann A, Trevanion S, White S, Wilder SP, Aken BL, Birney E, Cunningham F, Dunham I, Harrow J, Herrero J, Hubbard TJ, Johnson N, Kinsella R, Parker A, Spudich G, Yates A, Zadissa A, Searle SM (2013) Ensembl 2013. Nucleic Acids Res 41:D48
Gojobori T, Li WH, Graur D (1982) Patterns of nucleotide substitution in pseudogenes and functional genes. J Mol Evol 18:360
Graul RC, Sadee W (1997) Evolutionary relationships among proteins probed by an iterative neighborhood cluster analysis (INCA). Alignment of bacteriorhodopsins with the yeast sequence YRO2. Pharm Res 14:1533
Green P (2007) 2x genomes–does depth matter? Genome Res 17:1547
Green P, Ewing B, Miller W, Thomas PJ, Green ED (2003) Transcription-associated mutational asymmetry in mammalian evolution. Nat Genet 33:514
Gu W, Wang X, Zhai C, Xie X, Zhou T (2012) Selection on synonymous sites for increased accessibility around miRNA binding sites in plants. Mol Biol Evol 29:3037
Hellmann I, Ebersberger I, Ptak SE, Paabo S, Przeworski M (2003a) A neutral explanation for the correlation of diversity with recombination rates in humans. Am J Hum Genet 72:1527
Hellmann I, Zollner S, Enard W, Ebersberger I, Nickel B, Paabo S (2003b) Selection on human genes as revealed by comparisons to chimpanzee cDNA. Genome Res 13:831
Hellmann I, Prufer K, Ji H, Zody MC, Paabo S, Ptak SE (2005) Why do human diversity levels vary at a megabase scale? Genome Res 15:1222
Hurst LD (2006) Preliminary assessment of the impact of microRNA-mediated regulation on coding sequence evolution in mammals. J Mol Evol 63:174
Hurst LD, Williams EJ (2000) Covariation of GC content and the silent site substitution rate in rodents: implications for methodology and for the evolution of isochores. Gene 261:107
Hwang DG, Green P (2004) Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. Proc Natl Acad Sci USA 101:13994
Ikemura T (1985) Codon usage and tRNA content in unicellular and multicellular organisms. Mol Biol Evol 2:13
Kanaya S, Yamada Y, Kinouchi M, Kudo Y, Ikemura T (2001) Codon usage and tRNA genes in eukaryotes: correlation of codon usage diversity with translation efficiency and with CG-dinucleotide usage as assessed by multivariate analysis. J Mol Biol 53:290
Katoh K, Misawa K, Kuma K, Miyata T (2002) MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform. Nucleic Acids Res 30:3059
Keightley PD, Halligan DL (2011) Inference of site frequency spectra from high-throughput sequence data: quantification of selection on nonsynonymous and synonymous sites in humans. Genetics 188:931
Keightley PD, Eory L, Halligan DL, Kirkpatrick M (2011) Inference of mutation parameters and selective constraint in mammalian coding sequences by approximate Bayesian computation. Genetics 187:1153
Koren A, Polak P, Nemesh J, Michaelson JJ, Sebat J, Sunyaev SR, McCarroll SA (2012) Differential relationship of DNA replication timing to different forms of human mutation and variation. Am J Hum Genet 91:1033
Kumar S (2005) Molecular clocks: four decades of evolution. Nat Rev Genet 6:654
Kumar S, Subramanian S (2002) Mutation rates in mammalian genomes. Proc Natl Acad Sci USA 99:803
Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, Devon K, Dewar K, Doyle M, FitzHugh W, Funke R, Gage D, Harris K, Heaford A, Howland J, Kann L, Lehoczky J, LeVine R, McEwan P, McKernan K, Meldrim J, Mesirov JP, Miranda C, Morris W, Naylor J, Raymond C, Rosetti M, Santos R, Sheridan A, Sougnez C, Stange-Thomann N, Stojanovic N, Subramanian A, Wyman D, Rogers J, Sulston J, Ainscough R, Beck S, Bentley D, Burton J, Clee C, Carter N, Coulson A, Deadman R, Deloukas P, Dunham A, Dunham I, Durbin R, French L, Grafham D, Gregory S, Hubbard T, Humphray S, Hunt A, Jones M, Lloyd C, McMurray A, Matthews L, Mercer S, Milne S, Mullikin JC, Mungall A, Plumb R, Ross M, Shownkeen R, Sims S, Waterston RH, Wilson RK, Hillier LW, McPherson JD, Marra MA, Mardis ER, Fulton LA, Chinwalla AT, Pepin KH, Gish WR, Chissoe SL, Wendl MC, Delehaunty KD, Miner TL, Delehaunty A, Kramer JB, Cook LL, Fulton RS, Johnson DL, Minx PJ, Clifton SW, Hawkins T, Branscomb E, Predki P, Richardson P, Wenning S, Slezak T, Doggett N, Cheng JF, Olsen A, Lucas S, Elkin C, Uberbacher E, Frazier M, Gibbs RA, Muzny DM, Scherer SE, Bouck JB, Sodergren EJ, Worley KC, Rives CM, Gorrell JH, Metzker ML, Naylor SL, Kucherlapati RS, Nelson DL, Weinstock GM, Sakaki Y, Fujiyama A, Hattori M, Yada T, Toyoda A, Itoh T, Kawagoe C, Watanabe H, Totoki Y, Taylor T, Weissenbach J, Heilig R, Saurin W, Artiguenave F, Brottier P, Bruls T, Pelletier E, Robert C, Wincker P, Smith DR, Doucette-Stamm L, Rubenfield M, Weinstock K, Lee HM, Dubois J, Rosenthal A, Platzer M, Nyakatura G, Taudien S, Rump A, Yang H, Yu J, Wang J, Huang G, Gu J, Hood L, Rowen L, Madan A, Qin S, Davis RW, Federspiel NA, Abola AP, Proctor MJ, Myers RM, Schmutz J, Dickson M, Grimwood J, Cox DR, Olson MV, Kaul R, Shimizu N, Kawasaki K, Minoshima S, Evans GA, Athanasiou M, Schultz R, Roe BA, Chen F, Pan H, Ramser J, Lehrach H, Reinhardt R, McCombie WR, de la Bastide M, Dedhia N, Blocker H, Hornischer K, Nordsiek G, Agarwala R, Aravind L, Bailey JA, Bateman A, Batzoglou S, Birney E, Bork P, Brown DG, Burge CB, Cerutti L, Chen HC, Church D, Clamp M, Copley RR, Doerks T, Eddy SR, Eichler EE, Furey TS, Galagan J, Gilbert JG, Harmon C, Hayashizaki Y, Haussler D, Hermjakob H, Hokamp K, Jang W, Johnson LS, Jones TA, Kasif S, Kaspryzk A, Kennedy S, Kent WJ, Kitts P, Koonin EV, Korf I, Kulp D, Lancet D, Lowe TM, McLysaght A, Mikkelsen T, Moran JV, Mulder N, Pollara VJ, Ponting CP, Schuler G, Schultz J, Slater G, Smit AF, Stupka E, Szustakowski J, Thierry-Mieg D, Thierry-Mieg J, Wagner L, Wallis J, Wheeler R, Williams A, Wolf YI, Wolfe KH, Yang SP, Yeh RF, Collins F, Guyer MS, Peterson J, Felsenfeld A, Wetterstrand KA, Patrinos A, Morgan MJ, de Jong P, Catanese JJ, Osoegawa K, Shizuya H, Choi S, Chen YJ (2001) Initial sequencing and analysis of the human genome. Nature 409:860
Lawrie DS, Petrov DA, Messer PW (2011) Faster than neutral evolution of constrained sequences: the complex interplay of mutational biases and weak selection. Genome Biol Evol 3:383
Lawrie DS, Messer PW, Hershberg R, Petrov DA (2013) Strong purifying selection at synonymous sites in D. melanogaster. PLoS Genet 9:e1003527
Majewski J (2003) Dependence of mutational asymmetry on gene-expression levels in the human genome. Am J Hum Genet 73:688
McVean ATG, Charlesworth B (1999) A population genetic model for the evolution of synonymous codon usage: patterns and predictions. Genet Res 74:145
Meunier J, Duret L (2004) Recombination drives the evolution of GC-content in the human genome. Mol Biol Evol 21:984
Nikolaev SI, Montoya-Burgos JI, Popadin K, Parand L, Margulies EH, Antonarakis SE (2007) Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements. Proc Natl Acad Sci USA 104:20443
Notredame C, Abergel C (2003) Using multiple alignment methods to assess the quality of genomic data analysis. In: Andrade M (ed) Bioinformatics and genomes: current perspectives. Horizon Scientific Press, Wymondham (United Kingdom), pp 30–50
Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205
Ohta T (1973) Slightly deleterious mutant substitutions in evolution. Nature 246:96
Ophir R, Itoh T, Graur D, Gojobori T (1999) A simple method for estimating the intensity of purifying selection in protein-coding genes. Mol Biol Evol 16:49
Pagani F, Baralle FE (2004) Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genet 5:389
Parmley JL, Chamary JV, Hurst LD (2006) Evidence for purifying selection against synonymous mutations in mammalian exonic splicing enhancers. Mol Biol Evol 23:301
Phifer-Rixey M, Bonhomme F, Boursot P, Churchill GA, Pialek J, Tucker PK, Nachman MW (2012) Adaptive evolution and effective population size in wild house mice. Mol Biol Evol 29:2949
Piganeau G, Mouchiroud D, Duret L, Gautier C (2002) Expected relationship between the silent substitution rate and the GC content: implications for the evolution of isochores. J Mol Evol 54:129
Pink CJ, Hurst LD (2010) Timing of replication is a determinant of neutral substitution rates but does not explain slow Y chromosome evolution in rodents. Mol Biol Evol 27:1077
Popadin KY, Nikolaev SI, Junier T, Baranova M, Antonarakis SE (2013) Purifying selection in mammalian mitochondrial protein-coding genes is highly effective and congruent with evolution of nuclear genes. Mol Biol Evol 30:347
Ratnakumar A, Mousset S, Glemin S, Berglund J, Galtier N, Duret L, Webster MT (2010) Detecting positive selection within genomes: the problem of biased gene conversion. Philos Trans R Soc Lond B 365:2571
Rhind N, Gilbert DM (2013) DNA replication timing. Cold Spring Harb Perspect Biol 5:a010132
Romiguier J, Ranwez V, Douzery EJ, Galtier N (2013) Genomic evidence for large, long-lived ancestors to placental mammals. Mol Biol Evol 30:5
Schmegner C, Hameister H, Vogel W, Assum G (2007) Isochores and replication time zones: a perfect match. Cytogenet Genome Res 116:167
Schneider A, Dessimoz C, Gonnet GH (2007) OMA Browser–exploring orthologous relations across 352 complete genomes. Bioinformatics 23:2180
Siepel A, Haussler D (2004) Phylogenetic estimation of context-dependent substitution rates by maximum likelihood. Mol Biol Evol 21:468
Smith NG, Hurst LD (1998) Sensitivity of patterns of molecular evolution to alterations in methodology: a critique of Hughes and Yeager. J Mol Evol 47:493
Stamatoyannopoulos JA, Adzhubei I, Thurman RE, Kryukov GV, Mirkin SM, Sunyaev SR (2009) Human mutation rate associated with DNA replication timing. Nat Genet 41:393
Stergachis AB, Haugen E, Shafer A, Fu W, Vernot B, Reynolds A, Raubitschek A, Ziegler S, LeProust EM, Akey JM, Stamatoyannopoulos JA (2013) Exonic transcription factor binding directs codon choice and affects protein evolution. Science 342:1367
Stoletzki N, Eyre-Walker A (2007) Synonymous codon usage in Escherichia coli: selection for translational accuracy. Mol Biol Evol 24:374
Subramanian S, Kumar S (2003) Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes. Genome Res 13:838
The Chimpanzee Sequencing and Analysis Consortium (2005) Initial sequence of the chimpanzee genome and comparison with the human genome. Nature 437:69
Tyekucheva S, Makova KD, Karro JE, Hardison RC, Miller W, Chiaromonte F (2008) Human-macaque comparisons illuminate variation in neutral substitution rates. Genome Biol 9:R76
Vicoso B, Charlesworth B (2006) Evolution on the X chromosome: unusual patterns and processes. Nat Rev Genet 7:645
Wang Z, Rolish ME, Yeo G, Tung V, Mawson M, Burge CB (2004) Systematic identification and analysis of exonic splicing silencers. Cell 119:831
Wang Z, Xiao X, Van Nostrand E, Burge CB (2006) General and specific functions of exonic splicing silencers in splicing control. Mol Cell 23:61
Wolfe KH, Sharp PM, Li WH (1989) Mutation rates differ among regions of the mammalian genome. Nature 337:283
Woodfine K, Fiegler H, Beare DM, Collins JE, McCann OT, Young BD, Debernardi S, Mott R, Dunham I, Carter NP (2004) Replication timing of the human genome. Hum Mol Genet 13:191
Wright SI, Yau CB, Looseley M, Meyers BC (2004) Effects of gene expression on molecular evolution in Arabidopsis thaliana and Arabidopsis lyrata. Mol Biol Evol 21:1719
Yang Z (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 13:555
Yuan Q, Zhou Z, Lindell SG, Higley JD, Ferguson B, Thompson RC, Lopez JF, Suomi SJ, Baghal B, Baker M, Mash DC, Barr CS, Goldman D (2012) The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human. BMC Genet 13:52
Zhou T, Gu W, Wilke CO (2010) Detecting positive and purifying selection at synonymous sites in yeast and worm. Mol Biol Evol 27:1912