Farre Lab:Research

From OpenWetWare
Jump to navigationJump to search

Home        Research        Publications        People        Links        Teaching        Contact       

Circadian clocks

Circadian clocks have evolved to provide an adaptive advantage to most organisms that live under alternating cycles of light and darkness (Dodd et al., 2005; Ouyang et al., 1998; Woelfle et al., 2004). The clock provides a mechanism whereby physiological and behavioral processes can be performed at the appropriate times of day or night. Furthermore, the evolution of a true oscillator, rather than just a light-responsive sand-timer, enables organisms to predict the alterations that occur in relative proportion to day and night throughout the year in most clines. In mammals, many aspects of behavior and physiology are regulated by endogenous circadian clocks and are subject to daily oscillations (Hastings et al., 2003). In higher plants, the circadian clock regulates many key physiological processes, ranging from flowering time (Imaizumi and Kay, 2006; Yanovsky and Kay, 2003) and growth (Dowson-Day and Millar, 1999; Farre, 2012) to stomatal opening and CO2 assimilation (Farre and Weise, 2012). Moreover, in Arabidopsis thaliana the expression of at least 6% of the transcriptome is regulated by the circadian clock (Harmer et al., 2000; Michael and McClung, 2003; Schaffer et al., 2001), and recent findings show that the matching of internal and external cycles optimizes growth and survival (Dodd et al., 2005).

Figure 1
Figure 1

Circadian systems can be thought of consisting of 3 parts (Figure 1). The imput pathways are involved in the entrainment or reprograming of the central oscillator which is the core of the circadian system. In turn this molecular self-sustained oscillator regulates the different physiological processes by regulating output pathways.

Arabidopsis thaliana

We focus our work on the role of the PSEUDO-RESPONSE REGULATORS (PRR)(Farre and Liu, 2013). These proteins are not only involved in the regulation of the Arabidopsis circadian oscillator (Figure 2) but are also involved in the direct regulation of physiological processes (Huang et al., 2012; Liu et al., 2013; Nakamichi et al., 2012).

Figure 2
Figure 2

Figure 2. Current status of the Arabidopsis circadian clock (2014)

Nannochloropsis oceanica

Nannochloropsis species are small unicellular alga with a diameter of about 2 μm. Marine Nannochloropsis species are used as a source of fish food and omega-3 fatty acids (Adarme-Vega et al., 2012). Due to their high lipid content, which is particularly elevated under nitrogen deprivation, these species have been considered as a potential source of biofuels (Hu and Gao, 2003; Rodolfi et al., 2009; Van Vooren et al., 2012; Xu et al., 2004). The genomes of two Nannochloropsis species have been recently sequenced (Jinkerson et al., 2012; Pan et al., 2011; Radakovits et al., 2012; Vieler et al., 2012). Both species have a small genome of ~30 Mb, containing ~9,000-12,000 genes, similar to the diatoms Phaeodactylum tricornutum and Thalassiosira pseudonana (Armbrust et al., 2004; Bowler et al., 2008). Current research suggests that Nannochloropsis species are haploid and homologous gene replacement has been recently reported (Kilian et al., 2011; Pan et al., 2011). Cell division and lipid content are strongly diurnally regulated in Nannochloropsis (Fábregas et al., 2002; Sukenik and Carmeli, 1990).

The genome of N. oceanica CCMP1779 (Vieler et al., 2012) can be found here:http://genome.jgi.doe.gov/Nanoce1779/Nanoce1779.home.html

Clocks have been studied in cyanobacteria, plants, green alga, fungi and animals (Figure 3), however, the mechanisms underlying circadian rhythms in stramenopiles including Nannochloropsis are currently unknown. We have developed circadian reporter lines in different Nannochloropsis species and are currently characterizing their circadian rhythms and searching for clock components.

Figure 2
Figure 2

Figure 3. Overview of the presence of circadian oscillators in different taxa. Taxa in which circadian rhythms have been detected are in italics. Trc/Trl indicates the presence of a characterized transcriptional/translational circadian clock and the main components are indicated. Trc-less indicates the presence of oscillations of peroxiredoxin oxidation in the absence of transcription (PRX-ox). The green and red circles indicate secondary endosymbiotic events involving green and red alga respectively. Tree is based on tolweb.org.


  • Adarme-Vega TC, Lim DKY, Timmins M, Vernen F, Li Y, Schenk PM. 2012. Microalgal biofactories: a promising approach towards sustainable omega-3 fatty acid production. Microbial Cell Factories 11.
  • Armbrust EV, Berges JA, Bowler C, Green BR, Martinez D, Putnam NH, Zhou SG, Allen AE, Apt KE, Bechner M, Brzezinski MA, Chaal BK, Chiovitti A, Davis AK, Demarest MS, Detter JC, Glavina T, Goodstein D, Hadi MZ, Hellsten U, Hildebrand M, Jenkins BD, Jurka J, Kapitonov VV, Kroger N, Lau WWY, Lane TW, Larimer FW, Lippmeier JC, Lucas S, Medina M, Montsant A, Obornik M, Parker MS, Palenik B, Pazour GJ, Richardson PM, Rynearson TA, Saito MA, Schwartz DC, Thamatrakoln K, Valentin K, Vardi A, Wilkerson FP, Rokhsar DS. 2004. The genome of the diatom Thalassiosira pseudonana: Ecology, evolution, and metabolism. Science 306, 79-86.
  • Bowler C, Allen AE, Badger JH, Grimwood J, Jabbari K, Kuo A, Maheswari U, Martens C, Maumus F, Otillar RP, Rayko E, Salamov A, Vandepoele K, Beszteri B, Gruber A, Heijde M, Katinka M, Mock T, Valentin K, Verret F, Berges JA, Brownlee C, Cadoret JP, Chiovitti A, Choi CJ, Coesel S, De Martino A, Detter JC, Durkin C, Falciatore A, Fournet J, Haruta M, Huysman MJJ, Jenkins BD, Jiroutova K, Jorgensen RE, Joubert Y, Kaplan A, Kroger N, Kroth PG, La Roche J, Lindquist E, Lommer M, Martin-Jezequel V, Lopez PJ, Lucas S, Mangogna M, McGinnis K, Medlin LK, Montsant A, Oudot-Le Secq MP, Napoli C, Obornik M, Parker MS, Petit JL, Porcel BM, Poulsen N, Robison M, Rychlewski L, Rynearson TA, Schmutz J, Shapiro H, Siaut M, Stanley M, Sussman MR, Taylor AR, Vardi A, von Dassow P, Vyverman W, Willis A, Wyrwicz LS, Rokhsar DS, Weissenbach J, Armbrust EV, Green BR, Van De Peer Y, Grigoriev IV. 2008. The Phaeodactylum genome reveals the evolutionary history of diatom genomes. Nature 456, 239-244.
  • Dodd AN, Salathia N, Hall A, Kevei E, Toth R, Nagy F, Hibberd JM, Millar AJ, Webb AA. 2005. Plant circadian clocks increase photosynthesis, growth, survival, and competitive advantage. Science 309, 630-633.
  • Dowson-Day MJ, Millar AJ. 1999. Circadian dysfunction causes aberrant hypocotyl elongation patterns in Arabidopsis. Plant Journal 17, 63-71.
  • Fábregas J, Maseda A, Domínguez A, Ferreira M, Otero A. 2002. Changes in the cell composition of the marine microalga, Nannochloropsis gaditana, during a light:dark cycle. Biotechnology Letters 24, 1699-1703.
  • Farre EM. 2012. The regulation of plant growth by the circadian clock. Plant Biology (Stuttgart) 14, 401-410.
  • Farre EM, Liu T. 2013. The PRR family of transcriptional regulators reflects the complexity and evolution of plant circadian clocks. Current Opinion in Plant Biology Epub.
  • Farre EM, Weise SE. 2012. The interactions between the circadian clock and primary metabolism. Current Opinion in Plant Biology 15, 293-300.
  • Harmer SL, Hogenesch JB, Straume M, Chang HS, Han B, Zhu T, Wang X, Kreps JA, Kay SA. 2000. Orchestrated transcription of key pathways in Arabidopsis by the circadian clock. Science 290, 2110-2113.
  • Hastings MH, Reddy AB, Maywood ES. 2003. A clockwork web: circadian timing in brain and periphery, in health and disease. Nature Reviews Neuroscience 4, 649-661.
  • Hu H, Gao K. 2003. Optimization of growth and fatty acid composition of a unicellular marine picoplankton, Nannochloropsis sp., with enriched carbon sources. Biotechnology Letters 25, 421-425.
  • Huang W, Perez-Garcia P, Pokhilko A, Millar AJ, Antoshechkin I, Riechmann JL, Mas P. 2012. Mapping the core of the Arabidopsis circadian clock defines the network structure of the oscillator. Science 336, 75-79.
  • Imaizumi T, Kay SA. 2006. Photoperiodic control of flowering: not only by coincidence. Trends in Plant Science 11, 550-558.
  • Jinkerson RE, Radakovits R, Posewitz MC. 2012. Genomic insights from the oleaginous model alga Nannochloropsis gaditana. Bioengineered 4, 1-7.
  • Kilian O, Benemann CSE, Niyogi KK, Vick B. 2011. High-efficiency homologous recombination in the oil-producing alga Nannochloropsis sp. Proceedings of the National Academy of Sciences of the United States of America 108, 21265-21269.
  • Liu T, Carlsson J, Takeuchi T, Newton L, Farre EM. 2013. Direct regulation of abiotic responses by the Arabidopsis circadian clock component PRR7. Plant Journal Epub.
  • Michael TP, McClung CR. 2003. Enhancer trapping reveals widespread circadian clock transcriptional control in Arabidopsis. Plant Physiology 132, 629-639.
  • Nakamichi N, Kiba T, Kamioka M, Suzuki T, Yamashino T, Higashiyama T, Sakakibara H, Mizuno T. 2012. Transcriptional repressor PRR5 directly regulates clock-output pathways. Proceedings of the National Academy of Sciences of the United States of America 109, 17123-17128.
  • Ouyang Y, Andersson CR, Kondo T, Golden SS, Johnson CH. 1998. Resonating circadian clocks enhance fitness in cyanobacteria. Proceedings of the National Academy of Sciences of the United States of America 95, 8660-8664.
  • Pan K, Qin J, Li S, Dai W, Zhu B, Jin Y, Yu W, Yang G, Li D. 2011. Nuclear monoploidy and asexual propagation of Nannochloropsis oceanica (Eustigmatophyceae) as revealed by its genome sequence. Journal of Phycology 47, 1425-1432.
  • Radakovits R, Jinkerson RE, Fuerstenberg SI, Tae H, Settlage RE, Boore JL, Posewitz MC. 2012. Draft genome sequence and genetic transformation of the oleaginous alga Nannochloropis gaditana. Nature Communications 3.
  • Rodolfi L, Zittelli GC, Bassi N, Padovani G, Biondi N, Bonini G, Tredici MR. 2009. Microalgae for Oil: Strain Selection, Induction of Lipid Synthesis and Outdoor Mass Cultivation in a Low-Cost Photobioreactor. Biotechnology and Bioengineering 102, 100-112.
  • Schaffer R, Landgraf J, Accerbi M, Simon V, Larson M, Wisman E. 2001. Microarray analysis of diurnal and circadian-regulated genes in Arabidopsis. Plant Cell 13, 113-123.
  • Van Vooren G, Le Grand F, Legrand J, Cuine S, Peltier G, Pruvost J. 2012. Investigation of fatty acids accumulation in Nannochloropsis oculata for biodiesel application. Bioresource Technology 124, 421-432.
  • Vieler A, Wu G, Tsai CH, Bullard B, Cornish AJ, Harvey C, Reca IB, Thornburg C, Achawanantakun R, Buehl CJ, Campbell MS, Cavalier D, Childs KL, Clark TJ, Deshpande R, Erickson E, Armenia Ferguson A, Handee W, Kong Q, Li X, Liu B, Lundback S, Peng C, Roston RL, Sanjaya, Simpson JP, Terbush A, Warakanont J, Zauner S, Farre EM, Hegg EL, Jiang N, Kuo MH, Lu Y, Niyogi KK, Ohlrogge J, Osteryoung KW, Shachar-Hill Y, Sears BB, Sun Y, Takahashi H, Yandell M, Shiu SH, Benning C. 2012. Genome, Functional Gene Annotation, and Nuclear Transformation of the Heterokont Oleaginous Alga Nannochloropsis oceanica CCMP1779. PLoS Genetics 8, e1003064.
  • Woelfle MA, Ouyang Y, Phanvijhitsiri K, Johnson CH. 2004. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Current Biology 14, 1481-1486.
  • Xu F, Cai ZL, Cong W, Ouyang F. 2004. Growth and fatty acid composition of Nannochloropsis sp. grown mixotrophically in fed-batch culture. Biotechnology Letters 26, 1319-1322.