A millifluidic study of cell-to-cell heterogeneity in growth-rate and cell-division capability in populations of isogenic cells of Chlamydomonas reinhardtii

PLoS ONE

Volumn 10, Issue 3, 2015, Pages

  Damodaran, Shima P ^a   Eberhard, Stephan ^b,d   Boitard, Laurent ^a   Rodriguez, Jairo Garnica ^a   Wang, Yuxing ^a,c   Bremond, Nicolas ^a   Baudry, Jean ^a   Bibette, Jérôme ^a   Wollman, Francis André ^b  

^a PSL RESEARCH UNIVERSITY   (France)

^b National de la Recherche Scientifique Université Pierre et Marie Curie   (France)

^c Optical Science and Engineering Research Center Department of Physics and Astronomy   (China)

^d SORBONNE UNIVERSITÉ   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AGAR;

ARTICLE; CELL AGING; CELL COUNT; CELL DIVISION; CELL GROWTH; CELL HETEROGENEITY; CELL POPULATION; CELL SUBPOPULATION; CELL SYNCHRONIZATION; CHEMICAL ANALYSIS; CHLAMYDOMONAS REINHARDTII; CONTROLLED STUDY; EUKARYOTE; GENE MUTATION; GROWTH RATE; MACROMOLECULE; MILLIFLUIDIC ANALYSIS; MIXOTROPH; NONHUMAN; PROKARYOTE; STEM CELL; CELL CULTURE; CELL PROLIFERATION; CULTURE TECHNIQUE; CYTOLOGY; DEVICES; GROWTH, DEVELOPMENT AND AGING; LAB ON A CHIP;

ALGAE; CHLAMYDOMONAS REINHARDTII; PROKARYOTA;

CELL CULTURE TECHNIQUES; CELL DIVISION; CELL PROLIFERATION; CELLS, CULTURED; CHLAMYDOMONAS REINHARDTII; LAB-ON-A-CHIP DEVICES;

EID: 84924587609     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0118987     Document Type: Article

References (123)

1. Maloney PC, Rotman B. Distribution of Suboptimally Induced beta-D-Galactosidase in Escherichia coli. The Enzyme Content of Individual Cells. J Mol Biol. 1973; 73: 77-91 PMID: 4570383
2. Spudich JL, Koshland DE Jr. Non-genetic individuality: chance in the single cell. Nature. 1976; 262: 467-471 PMID: 958399
3. Schaeffer P, Millet J, Aubert JP. Catabolic repression of bacterial sporulation. Proc Natl Acad Sci U S A. 1965; 54: 704-711 PMID: 4956288
4. Haijema B-J, Hahn J, Haynes J, Dubnau D. A ComGA-dependent checkpoint limits growth during the escape from competence. Mol Microbiol. 2001; 40: 52-64 PMID: 11298275
5. Brehm-Stecher BF, Johnson EA. Single-cell microbiology: tools, technologies, and applications. Microbiol Mol Biol Rev. 2004; 68: 538-559, table of contents PMID: 15353569
6. Lidstrom ME, Konopka MC. The role of physiological heterogeneity in microbial population behavior. Nat Chem Biol. 2010; 6: 705-712 doi: 10.1038/nchembio.436 PMID: 20852608
7. Loewer A, Lahav G. We are all individuals: causes and consequences of non-genetic heterogeneity in mammalian cells. Curr Opin Genet Dev. 2011; 21: 753-758 doi: 10.1016/j.gde.2011.09.010 PMID: 22005655
8. Levchenko A, Nemenman I. Cellular noise and information transmission. Curr Opin Biotechnol. 2014;28C: 156-164
9. Capp JP. Noise-driven heterogeneity in the rate of genetic-variant generation as a basis for evolvability. Genetics. 2010; 185: 395-404 doi: 10.1534/genetics.110.118190 PMID: 20606014
10. Sanchez A, Choubey S, Kondev J. Regulation of noise in gene expression. Annu Rev Biophys. 2013; 42: 469-491 doi: 10.1146/annurev-biophys-083012-130401 PMID: 23527780
11. McAdams HH, Arkin A. Stochastic mechanisms in gene expression. Proc Natl Acad Sci U S A. 1997; 94: 814-819 PMID: 9023339
12. Skommer J, Raychaudhuri S, Wlodkowic D. Timing is everything: stochastic origins of cell-to-cell variability in cancer cell death. Front Biosci (Landmark Ed). 2011; 16: 307-314 PMID: 21196172
13. Wu J, Tzanakakis ES. Deconstructing stem cell population heterogeneity: single-cell analysis and modeling approaches. Biotechnol Adv. 2013; 31: 1047-1062 doi: 10.1016/j.biotechadv.2013.09.001 PMID: 24035899
14. Huang S. Non-genetic heterogeneity of cells in development: more than just noise. Development. 2009; 136: 3853-3862 doi: 10.1242/dev.035139 PMID: 19906852
15. Colman-Lerner A, Gordon A, Serra E, Chin T, Resnekov O, Endy D, et al. Regulated cell-to-cell variation in a cell-fate decision system. Nature. 2005; 437: 699-706 PMID: 16170311
16. Mortimer RK, Johnston JR. Life span of individual yeast cells. Nature. 1959; 183: 1751-1752 PMID: 13666896
17. Wright WE, Shay JW. Historical claims and current interpretations of replicative aging. Nat Biotechnol. 2002; 20: 682-688 PMID: 12089552
18. Steinkraus KA, Kaeberlein M, Kennedy BK. Replicative aging in yeast: the means to the end. Annu Rev Cell Dev Biol. 2008; 24: 29-54 doi: 10.1146/annurev.cellbio.23.090506.123509 PMID: 18616424
19. Longo VD, Fabrizio P. Chronological Aging in Saccharomyces cerevisiae. Subcell Biochem. 2012; 57: 101-121 doi: 10.1007/978-94-007-2561-4-5 PMID: 22094419
20. Pan Y. Mitochondria, reactive oxygen species, and chronological aging: a message from yeast. Exp Gerontol. 2011; 46: 847-852 doi: 10.1016/j.exger.2011.08.007 PMID: 21884780
21. Longo VD, Shadel GS, Kaeberlein M, Kennedy B. Replicative and chronological aging in Saccharomyces cerevisiae. Cell Metab. 2012; 16: 18-31 doi: 10.1016/j.cmet.2012.06.002 PMID: 22768836
22. Roux AE, Chartrand P, Ferbeyre G, Rokeach LA. Fission yeast and other yeasts as emergent models to unravel cellular aging in eukaryotes. J Gerontol A Biol Sci Med Sci. 2010; 65: 1-8 doi: 10.1093/ gerona/glp152 PMID: 19875745
23. Vachova L, Cap M, Palkova Z. Yeast colonies: a model for studies of aging, environmental adaptation, and longevity. Oxid Med Cell Longev. 2012; 2012: 601836 doi: 10.1155/2012/601836 PMID: 22928081
24. Barker MG, Walmsley RM. Replicative ageing in the fission yeast Schizosaccharomyces pombe. Yeast. 1999; 15: 1511-1518 PMID: 10514568
25. Amann R, Fuchs BM. Single-cell identification in microbial communities by improved fluorescence in situ hybridization techniques. Nat Rev Microbiol. 2008; 6: 339-348 doi: 10.1038/nrmicro1888 PMID: 18414500
26. Boedicker JQ, Vincent ME, Ismagilov RF. Microfluidic confinement of single cells of bacteria in small volumes initiates high-density behavior of quorum sensing and growth and reveals its variability. Angew Chem Int Ed Engl. 2009; 48: 5908-5911 doi: 10.1002/anie.200901550 PMID: 19565587
27. Boitard L, Cottinet D, Kleinschmitt C, Bremond N, Baudry J, Yvert G, et al. Monitoring single-cell bioenergetics via the coarsening of emulsion droplets. Proc Natl Acad Sci U S A. 2012; 109: 7181-7186 doi: 10.1073/pnas.1200894109 PMID: 22538813
28. Czechowska K, Johnson DR, van der Meer JR. Use of flow cytometric methods for single-cell analysis in environmental microbiology. Current Opinion in Microbiology. 2008; 11: 205-212 doi: 10.1016/j. mib.2008.04.006 PMID: 18562243
29. Dichosa AE, Daughton AR, Reitenga KG, Fitzsimons MS, Han CS. Capturing and cultivating single bacterial cells in gel microdroplets to obtain near-complete genomes. Nat Protoc. 2014; 9: 608-621 doi: 10.1038/nprot.2014.034 PMID: 24525754
30. Garay LA, Boundy-Mills KL, German JB. Accumulation of high value lipids in single cell microorganisms: A mechanistic approach and future perspectives. J Agric Food Chem. 2014;
31. Garz A, Sandmann M, Rading M, Ramm S, Menzel R, Steup M. Cell-to-cell diversity in a synchronized Chlamydomonas culture as revealed by single-cell analyses. Biophys J. 2012; 103: 1078-1086 PMID: 23009858
32. Grunberger A, Wiechert W, Kohlheyer D. Single-cell microfluidics: opportunity for bioprocess development. Curr Opin Biotechnol. 2014; 29C: 15-23
33. Hofer U. Environmental microbiology: Exploring diversity with single-cell genomics. Nat Rev Microbiol. 2013; 11: 598 doi: 10.1038/nrmicro3094 PMID: 23893104
34. Matsumura K, Yagi T, Hattori A, Soloviev M, Yasuda K. Using single cell cultivation system for on-chip monitoring of the interdivision timer in Chlamydomonas reinhardtii cell cycle. J Nanobiotechnology. 2010; 8: 23 doi: 10.1186/1477-3155-8-23 PMID: 20868509
35. Shapiro E, Biezuner T, Linnarsson S. Single-cell sequencing-based technologies will revolutionize whole-organism science. Nat Rev Genet. 2013; 14: 618-630 doi: 10.1038/nrg3542 PMID: 23897237
36. Stepanauskas R. Single cell genomics: an individual look at microbes. Current Opinion in Microbiology. 2012; 15: 613-620 doi: 10.1016/j.mib.2012.09.001 PMID: 23026140
37. Yin H, Marshall D. Microfluidics for single cell analysis. Curr Opin Biotechnol. 2012; 23: 110-119 doi: 10.1016/j.copbio.2011.11.002 PMID: 22133547
38. Eun YJ, Utada AS, Copeland MF, Takeuchi S,Weibel DB. Encapsulating bacteria in agarose microparticles using microfluidics for high-throughput cell analysis and isolation. ACS Chem Biol. 2011; 6: 260-266 doi: 10.1021/cb100336p PMID: 21142208
39. Hoeck C (1995) Algae: an introduction to phycology: Cambridge University Press.
40. Richmond A (2008) Handbook of microalgal culture: biotechnology and applied phycology: John Wiley & Sons.
41. Leon R, Galvan A, Fernandez E (2007) Transgenic Microalgae as Green Cell Factories. Springer Science and Business Media, New-York, USA: Landes Bioscience.
42. Gimpel JA, Specht EA, Georgianna DR, Mayfield SP. Advances in microalgae engineering and synthetic biology applications for biofuel production. Curr Opin Chem Biol. 2013; 17: 489-495 doi: 10. 1016/j.cbpa.2013.03.038 PMID: 23684717
43. Jones CS, Mayfield SP. Algae biofuels: versatility for the future of bioenergy. Curr Opin Biotechnol. 2012; 23: 346-351 doi: 10.1016/j.copbio.2011.10.013 PMID: 22104720
44. Esquivel MG, Amaro HM, Pinto TS, Fevereiro PS, Malcata FX. Efficient H2 production via Chlamydomonas reinhardtii. Trends Biotechnol. 2011; 29: 595-600 doi: 10.1016/j.tibtech.2011.06.008 PMID: 21794941
45. Ghysels B, Franck F. Hydrogen photo-evolution upon S deprivation stepwise: an illustration of microalgal photosynthetic and metabolic flexibility and a step stone for future biotechnological methods of renewable H(2) production. Photosynth Res. 2010; 106: 145-154 doi: 10.1007/s11120-010-9582-4 PMID: 20658193
46. Rupprecht J. From systems biology to fuel-Chlamydomonas reinhardtii as a model for a systems biology approach to improve biohydrogen production. J Biotechnol. 2009; 142: 10-20 doi: 10.1016/j. jbiotec.2009.02.008 PMID: 19480943
47. Scott SA, Davey MP, Dennis JS, Horst I, Howe CJ, Lea-Smith DJ, et al. Biodiesel from algae: challenges and prospects. Curr Opin Biotechnol. 2010; 21: 277-286 doi: 10.1016/j.copbio.2010.03.005 PMID: 20399634
48. Brennan L, Owende P. Biofuels from microalgae-A review of technologies for production, processing, and extractions of biofuels and co-products. Renewable and Sustainable Energy Reviews. 2010; 14: 557-577
49. Bae S, Kim CW, Choi JS, Yang JW, Seo TS. An integrated microfluidic device for the high-throughput screening of microalgal cell culture conditions that induce high growth rate and lipid content. Anal Bioanal Chem. 2013; 405: 9365-9374 doi: 10.1007/s00216-013-7389-9 PMID: 24170268
50. Yu WL, AnsariW, Schoepp NG, Hannon MJ, Mayfield SP, Burkart MD. Modifications of the metabolic pathways of lipid and triacylglycerol production in microalgae. Microb Cell Fact. 2011; 10: 91 doi: 10. 1186/1475-2859-10-91 PMID: 22047615
51. Blaby IK, Blaby-Haas CE, Tourasse N, Hom EF, Lopez D, Aksoy M, et al. The Chlamydomonas genome project: a decade on. Trends Plant Sci. 2014;
52. Proschold T, Harris EH, Coleman AW. Portrait of a species: Chlamydomonas reinhardtii. Genetics. 2005; 170: 1601-1610 PMID: 15956662
53. Harris EH. Chlamydomonas as a model organism. Annual Review of Plant Physiology and Plant Molecular Biology. 2001; 52: 363-406 PMID: 11337403
54. Rochaix JD. Chlamydomonas, a model system for studying the assembly and dynamics of photosynthetic complexes. FEBS Lett. 2002; 529: 34-38 PMID: 12354609
55. Rochaix JD. The three genomes of Chlamydomonas. Photosynth Res. 2002; 73: 285-293 PMID: 16245133
56. Hippler M, Redding K, Rochaix JD. Chlamydomonas genetics, a tool for the study of bioenergetic pathways. Biochim Biophys Acta. 1998; 1367: 1-62 PMID: 9784589
57. Rochaix JD. Chlamydomonas reinhardtii as the photosynthetic yeast. Annu Rev Genet. 1995; 29: 209-230 PMID: 8825474
58. Harris EH (2009) The Chlamydomonas Sourcebook (Second Edition). Canada: Elsevier Academic Press.
59. Merchant SS, Prochnik SE, Vallon O, Harris EH, Karpowicz SJ, Witman GB, et al. The Chlamydomonas genome reveals the evolution of key animal and plant functions. Science. 2007; 318: 245-250 PMID: 17932292
60. Grossman AR, Harris EE, Hauser C, Lefebvre PA, Martinez D, Rokhsar D, et al. Chlamydomonas reinhardtii at the crossroads of genomics. Eukaryot Cell. 2003; 2: 1137-1150 PMID: 14665449
61. Grossman AR. Chlamydomonas reinhardtii and photosynthesis: genetics to genomics. Curr Opin Plant Biol. 2000; 3: 132-137 PMID: 10712957
62. Eberhard S, Finazzi G, Wollman FA. The dynamics of photosynthesis. Annu Rev Genet. 2008; 42: 463-515 doi: 10.1146/annurev.genet.42.110807.091452 PMID: 18983262
63. Wollman FA, Minai L, Nechushtai R. The biogenesis and assembly of photosynthetic proteins in thylakoid membranes1. Biochim Biophys Acta. 1999; 1411: 21-85 PMID: 10216153
64. Silflow CD, Lefebvre PA. Assembly and motility of eukaryotic cilia and flagella. Lessons from Chlamydomonas reinhardtii. Plant Physiol. 2001; 127: 1500-1507 PMID: 11743094
65. Snell WJ, Pan J, Wang Q. Cilia and flagella revealed: from flagellar assembly in Chlamydomonas to human obesity disorders. Cell. 2004; 117: 693-697 PMID: 15186771
66. Lee L. Mechanisms of mammalian ciliary motility: Insights from primary ciliary dyskinesia genetics. Gene. 2011; 473: 57-66 doi: 10.1016/j.gene.2010.11.006 PMID: 21111794
67. Pan J, Wang Q, Snell WJ. Cilium-generated signaling and cilia-related disorders. Lab Invest. 2005; 85: 452-463 PMID: 15723088
68. Rosales-Mendoza S, Paz-Maldonado LM, Soria-Guerra RE. Chlamydomonas reinhardtii as a viable platform for the production of recombinant proteins: current status and perspectives. Plant Cell Rep. 2012; 31: 479-494 doi: 10.1007/s00299-011-1186-8 PMID: 22080228
69. Mayfield SP, Manuell AL, Chen S, Wu J, Tran M, Siefker D, et al. Chlamydomonas reinhardtii chloroplasts as protein factories. Curr Opin Biotechnol. 2007; 18: 126-133 PMID: 17317144
70. Specht EA, Mayfield SP. Algae-based oral recombinant vaccines. Front Microbiol. 2014; 5: 60 doi: 10.3389/fmicb.2014.00060 PMID: 24596570
71. Spolaore P, Joannis-Cassan C, Duran E, Isambert A. Commercial applications of microalgae. J Biosci Bioeng. 2006; 101: 87-96 PMID: 16569602
72. Skjanes K, Rebours C, Lindblad P. Potential for green microalgae to produce hydrogen, pharmaceuticals and other high value products in a combined process. Crit Rev Biotechnol. 2013; 33: 172-215 doi: 10.3109/07388551.2012.681625 PMID: 22765907
73. Velmurugan N, Sung M, Yim SS, Park MS, Yang JW, Jeong KJ. Evaluation of intracellular lipid bodies in Chlamydomonas reinhardtii strains by flow cytometry. Bioresour Technol. 2013; 138: 30-37 doi: 10.1016/j.biortech.2013.03.078 PMID: 23612159
74. Lee DH, Bae CY, Han JI, Park JK. In situ analysis of heterogeneity in the lipid content of single green microalgae in alginate hydrogel microcapsules. Anal Chem. 2013; 85: 8749-8756 doi: 10.1021/ ac401836j PMID: 24007509
75. Pan J, Stephenson AL, Kazamia E, Huck WT, Dennis JS, Smith AG, et al. Quantitative tracking of the growth of individual algal cells in microdroplet compartments. Integr Biol (Camb). 2011; 3: 1043-1051 doi: 10.1039/c1ib00033k PMID: 21863189
76. Dewan A, Kim J, McLean RH, Vanapalli SA, Karim MN. Growth kinetics of microalgae in microfluidic static droplet arrays. Biotechnol Bioeng. 2012; 109: 2987-2996 doi: 10.1002/bit.24568 PMID: 22711504
77. Baraban L, Bertholle F, Salverda ML, Bremond N, Panizza P, Baudry J, et al. Millifluidic droplet analyser for microbiology. Lab Chip. 2011; 11: 4057-4062 doi: 10.1039/c1lc20545e PMID: 22012599
78. Harris EH (1989) The Chlamydomonas Sourcebook. A Comprehensive Guide to Biology and Laboratory Use; Press A, editor. San Diego, CA, USA. PMID: 17756009
79. Fischer BB, Wiesendanger M, Eggen RI. Growth condition-dependent sensitivity, photodamage and stress response of Chlamydomonas reinhardtii exposed to high light conditions. Plant Cell Physiol. 2006; 47: 1135-1145 PMID: 16857695
80. Spudich JL, Sager R. Regulation of the Chlamydomonas cell cycle by light and dark. J Cell Biol. 1980; 85: 136-145 PMID: 6767730
81. Lemaire SD, Hours M, Gerard-Hirne C, Trouabal A, Roche O, Jacquot JP. Analysis of light/dark synchronization of cell-wall-less Chlamydomonas reinhardtii (Chlorophyta) cells by flow cytometry. Eur J Phycol. 1999; 34: 279-286
82. Kürsten D, Cao J, Funfak A, Müller P, Köhler JM. Cultivation of Chlorella vulgaris in microfluid segments and microtoxicological determination of their sensitivity against CuCl2 in the nanoliter range. Engineering in Life Sciences. 2011; 11: 580-587
83. Ratcliff WC, Herron MD, Howell K, Pentz JT, Rosenzweig F, Travisano M. Experimental evolution of an alternating uni- and multicellular life cycle in Chlamydomonas reinhardtii. Nat Commun. 2013; 4: 2742 doi: 10.1038/ncomms3742 PMID: 24193369
84. Strovas TJ, Sauter LM, Guo X, Lidstrom ME. Cell-to-cell heterogeneity in growth rate and gene expression in Methylobacterium extorquens AM1. J Bacteriol. 2007; 189: 7127-7133 PMID: 17644598
85. Gerdes K, Maisonneuve E. Bacterial persistence and toxin-antitoxin loci. Annu Rev Microbiol. 2012; 66: 103-123 doi: 10.1146/annurev-micro-092611-150159 PMID: 22994490
86. Maisonneuve E, Castro-Camargo M, Gerdes K. (p)ppGpp controls bacterial persistence by stochastic induction of toxin-antitoxin activity. Cell. 2013; 154: 1140-1150 doi: 10.1016/j.cell.2013.07.048 PMID: 23993101
87. Joers A, Kaldalu N, Tenson T. The frequency of persisters in Escherichia coli reflects the kinetics of awakening from dormancy. J Bacteriol. 2010; 192: 3379-3384 doi: 10.1128/JB.00056-10 PMID: 20435730
88. Moyed HS, Bertrand KP. hipA, a newly recognized gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis. J Bacteriol. 1983; 155: 768-775 PMID: 6348026
89. Claudi B, Sprote P, Chirkova A, Personnic N, Zankl J, Schurmann N, et al. Phenotypic variation of Salmonella in host tissues delays eradication by antimicrobial chemotherapy. Cell. 2014; 158: 722-733 doi: 10.1016/j.cell.2014.06.045 PMID: 25126781
90. Helaine S, Thompson JA, Watson KG, Liu M, Boyle C, Holden DW. Dynamics of intracellular bacterial replication at the single cell level. Proc Natl Acad Sci U S A. 2010; 107: 3746-3751 doi: 10.1073/ pnas.1000041107 PMID: 20133586
91. Helaine S, Holden DW. Heterogeneity of intracellular replication of bacterial pathogens. Curr Opin Microbiol. 2013; 16: 184-191 doi: 10.1016/j.mib.2012.12.004 PMID: 23485258
92. Demets R, Tomson AM, Ran ETH, Sigon CAM, Stegwee D, van den Ende H. Synchronization of the Cell Division Cycle of Chlamydomonas eugametos. Journal of General Microbiology. 1985; 131: 2919-2924
93. Stewart EJ, Madden R, Paul G, Taddei F. Aging and death in an organism that reproduces by morphologically symmetric division. PLoS Biol. 2005; 3: e45 PMID: 15685293
94. Rang CU, Peng AY, Chao L. Temporal dynamics of bacterial aging and rejuvenation. Curr Biol. 2011; 21: 1813-1816 doi: 10.1016/j.cub.2011.09.018 PMID: 22036179
95. Flatscher R, Frajman B, Schonswetter P, Paun O. Environmental heterogeneity and phenotypic divergence: can heritable epigenetic variation aid speciation? Genet Res Int. 2012; 2012: 698421 doi: 10. 1155/2012/698421 PMID: 22567398
96. Richards CL, Bossdorf O, Pigliucci M. What Role Does Heritable Epigenetic Variation Play in Phenotypic Evolution? BioScience. 2010; 60: 232-237
97. Strenkert D, Schmollinger S, Schroda M. Protocol: methodology for chromatin immunoprecipitation (ChIP) in Chlamydomonas reinhardtii. Plant Methods. 2011; 7: 35 doi: 10.1186/1746-4811-7-35 PMID: 22050920
98. Strenkert D, Schmollinger S, Sommer F, Schulz-Raffelt M, Schroda M. Transcription factor-dependent chromatin remodeling at heat shock and copper-responsive promoters in Chlamydomonas reinhardtii. Plant Cell. 2011; 23: 2285-2301 doi: 10.1105/tpc.111.085266 PMID: 21705643
99. Morgan AD, Ness RW, Keightley PD, Colegrave N. Spontaneous Mutation Accumulation in Multiple Strains of the Green Alga, Chlamydomonas Reinhardtii. Evolution. 2014;
100. Ness RW, Morgan AD, Colegrave N, Keightley PD. Estimate of the spontaneous mutation rate in Chlamydomonas reinhardtii. Genetics. 2012; 192: 1447-1454 doi: 10.1534/genetics.112.145078 PMID: 23051642
101. Perrineau MM, Gross J, Zelzion E, Price DC, Levitan O, Boyd J, et al. Using natural selection to explore the adaptive potential of Chlamydomonas reinhardtii. PLoS One. 2014; 9: e92533 doi: 10.1371/ journal.pone.0092533 PMID: 24658261
102. Sung W, Ackerman MS, Miller SF, Doak TG, Lynch M. Drift-barrier hypothesis and mutation-rate evolution. Proc Natl Acad Sci U S A. 2012; 109: 18488-18492 doi: 10.1073/pnas.1216223109 PMID: 23077252
103. Cooper VS. The origins of specialization: insights from bacteria held 25 years in captivity. PLoS Biol. 2014; 12: e1001790 doi: 10.1371/journal.pbio.1001790 PMID: 24558348
104. Wang P, Robert L, Pelletier J, Dang WL, Taddei F, Wright A, et al. Robust growth of Escherichia coli. Curr Biol. 2010; 20: 1099-1103 doi: 10.1016/j.cub.2010.04.045 PMID: 20537537
105. Wu B. A novel method to study aging in bacteria that reproduce by morphologically symmetric fission. J Theor Biol. 2013; 347C: 1-6
106. Kupiec M. Biology of telomeres: lessons from budding yeast. FEMS Microbiology Reviews. 2014; 38: 144-171 PMID: 24754043
107. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013; 75: 685-705 doi: 10. 1146/annurev-physiol-030212-183653 PMID: 23140366
108. Maklakov AA. Aging: why do organisms live too long? Curr Biol. 2013; 23: R1003-1005 doi: 10.1016/ j.cub.2013.10.002 PMID: 24262824
109. Rando TA. The ins and outs of aging and longevity. Annu Rev Physiol. 2013; 75: 617-619 doi: 10. 1146/annurev-physiol-092712-103439 PMID: 23398156
110. Vijg J, Suh Y. Genome instability and aging. Annu Rev Physiol. 2013; 75: 645-668 doi: 10.1146/ annurev-physiol-030212-183715 PMID: 23398157
111. Aguilera A, Garcia-Muse T. Causes of genome instability. Annu Rev Genet. 2013; 47: 1-32 doi: 10. 1146/annurev-genet-111212-133232 PMID: 23909437
112. Ghosh S, Zhou Z. Genetics of aging, progeria and lamin disorders. Curr Opin Genet Dev. 2014; 26C: 41-46
113. Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature. 1990; 345: 458-460 PMID: 2342578
114. Bernardes de Jesus B, Blasco MA. Telomerase at the intersection of cancer and aging. Trends Genet. 2013; 29: 513-520 doi: 10.1016/j.tig.2013.06.007 PMID: 23876621
115. Saeed H, Iqtedar M. Stem cell function and maintenance-ends that matter: Role of telomeres and telomerase. Journal of Biosciences. 2013; 38: 641-649 PMID: 23938394
116. Mason PJ, Perdigones N. Telomere biology and translational research. Transl Res. 2013; 162: 333-342 doi: 10.1016/j.trsl.2013.08.009 PMID: 24070997
117. Lundblad V, Szostak JW. A Mutant with a Defect in Telomere Elongation Leads to Senescence in Yeast. Cell. 1989; 57: 633-643 PMID: 2655926
118. Fulneckova J, Sevcikova T, Fajkus J, Lukesova A, Lukes M, Vlcek C, et al. A broad phylogenetic survey unveils the diversity and evolution of telomeres in eukaryotes. Genome Biol Evol. 2013; 5: 468-483 doi: 10.1093/gbe/evt019 PMID: 23395982
119. Hails T, Huttner O, Day A. Isolation of a Chlamydomonas reinhardtii telomere by functional complementation in yeast. Curr Genet. 1995; 28: 437-440 PMID: 8575016
120. Petracek ME, Berman J. Chlamydomonas reinhardtii telomere repeats form unstable structures involving guanine-guanine base pairs. Nucleic Acids Res. 1992; 20: 89-95 PMID: 1738609
121. Petracek ME, Konkel LMC, Kable ML, Berman J. A Chlamydomonas protein that binds singlestranded G-strand telomere DNA. EMBO J. 1994; 13: 3648-3658 PMID: 8062839
122. Petracek ME, Lefebvre PA, Silflow CD, Berman J. Chlamydomonas telomere sequences are A+Trich but contain three consecutiveGC basepairs. Proc Natl Acad Sci U S A. 1990; 87: 8222-8226 PMID: 2236035
123. Misumi O, Nishimura Y, Kuroiwa T. Effects of Chloroplast DNA Content on the Cell Proliferation and Aging in Chlamydomonas reinhardtii. Journal of Plant Research. 2001; 114: 125-131