
Rob McClung
215 Gilman
Hall
Genetics
And Molecular Genetics Of Plant Circadian Rhythms
The
ability of an organism to measure time is the product of a cellular biological
clock. Many phenomena controlled
by the biological clock cycle on a daily basis and are called circadian
rhythms. My goal is to understand
the genetic and biochemical mechanisms by which an organism measures time and
uses that temporal information to regulate gene expression and cellular
physiology. The circadian clock is
an endogenous oscillator that drives rhythms with periods of approximately 24
hours. By definition, these
circadian (from the Latin, circa,
approximately; dies, day) rhythms
persist in constant conditions and reflect the activity of an endogenous
biological clock. Plants are
richly rhythmic and the circadian clock regulates a number of key metabolic
pathways and stress responses. In
addition, the circadian clock plays a critical role in the photoperiodic
regulation of the transition to flowering in many species. Circadian rhythms in plants have been
the subject of a number of recent reviews, including several from my lab (SalomŽ and McClung,
2004, 2005a; McClung, 2006). It
is worth noting that two of these were largely taken from the introduction to
Patrice SalomŽÕs Ph.D. thesis.
1. Mutational Analysis of the Arabidopsis Circadian Clock. We have identified a number of loci which, when mutated, alter circadian rhythmicity (period or phase is altered, or the plants are arrhythmic). These studies include novel genes identified in forward genetic screens as well as defined genes identified through a candidate gene (reverse genetics) approach. The genetic and molecular biological analysis of these mutations offers a number of thesis projects (Michael et al., 2003; SalomŽ and McClung, 2005b, a).
2. Post-transcriptional Regulation by the
Arabidopsis Circadian Clock. The
biochemical function of the PRR proteins is not yet understood. However, it has become clear that the
stability of each is tightly regulated.
For example, TOC1 and PRR5 are targeted for proteasomal degradation
through interaction with the F-box protein ZTL. Each PRR is phosphorylated and this phosphorylation is
implicated in their regulated stability (Fujiwara et al., 2008). For example, the more highly
phosphorylated forms of PRR5 and TOC1 interact best with ZTL. This suggests that phosphorylation may
be an important step in the regulated proteolysis of the PRRs. What kinases are important for clock
function? We have recently
identified several kinases important for proper clock function and experiments
are in progress to identify the targets of these kinases and the biochemical
mechanisms by which phosphorylation contributes to clock function.
3. Evolutionary and Quantitative Genetic Analysis of the Arabidopsis Circadian Clock. PSEUDO-RESPONSE REGULATOR 7 (PRR7) is a gene that plays a role in the Arabidopsis thaliana circadian clock, because eliminating function of the PRR7 gene results in a lengthening of the circadian period. Also, we have mapped a number of loci (Quantitative Trait Loci; QTL) that contribute incrementally to the definition of period length and one of the QTLÕs mapped near PRR7 (Michael et al., 2003). We wish to determine whether PRR7 encodes a period QTL. If it does, we would predict there to be different PRR7 alleles among multiple accessions (natural populations). Sequence analysis confirms this prediction; most simply these can be divided into two clades that show distinct geographic distributions, with one clade in southwestern Europe and North Africa and the second clade in central and northeastern Europe. Excitingly, the distribution of mutations among these PRR7 alleles suggests that PRR7 is undergoing strong diversifying selection, consistent with the hypothesis that selection is acting to enrich multiple PRR7 forms, each of which is suited to a particular geographic habitat. Flanking genes fail to show similar distributions of mutations, consistent with natural selection acting on PRR7. We are extending this analysis to other Òclock genes,Ó including PRR9 and PRR1 (TOC1).
We intend to take two additional approaches concerning the identity of PRR7 as the QTL we identified. The first is a genetic approach in which we generate two sets of Near Isogenic Lines (NILs), in which the PRR7 allele from one Arabidopsis accession, Col, is introduced into a second accession, Ler and vice versa. One would predict that the Col and Ler PRR7 alleles would result in distinct periods. The second approach is more molecular biological. We would introduce the PRR7 alleles from several different accessions into a loss-of-function prr7 prr9 double mutant and ask whether each of the different alleles can restore PRR7 function equally well.
4. Evolutionary and Quantitative Genetic Analysis
of the Brassica rapa
Circadian Clock. We have started a new collaboration to look at clocks in a
crop species, Brassica rapa
(Chinese cabbage, turnip). We are measuring clock parameters (again, by
leaf movement) in order to map QTLs that contribute to period, phase and
amplitude. The study is ongoing,
but we already have identified multiple QTLs, one of
which maps near a B. rapa
PRR7 ortholog. In addition, we will map genes that
contribute to temperature entrainment and temperature compensation. Besides the QTL mapping, we will
identify B. rapa
orthologs of Arabidopsis clock genes and test whether they play similar roles
in the B. rapa clock.
Fujiwara, S., Wang, L., Han,
L., Suh, S.S., SalomŽ, P.A., McClung, C.R., and
Somers, D.E. (2008). Post-translational regulation
of the circadian clock through selective proteolysis and phosphorylation of
pseudo-response regulator proteins. J. Biol
Chem. 283, 23073-23083.
GutiŽrrez, R.A., Stokes, T.L., Thum,
K., Xu, X., Obertello, M., Katari, M.S., Tanurdzic, M.,
Dean, A., Nero, D.C., McClung, C.R., and Coruzzi, G.M.
(2008). Systems approach identifies an
organic nitrogen-responsive gene network that is regulated by the master clock
control gene CCA1. Proc. Natl. Acad.
Sci. USA 105, 4939-4944.
McClung,
C.R. (2006). Plant circadian rhythms. Plant Cell 18, 792-803.
Michael,
T.P., SalomŽ, P.A., Yu, H.J., Spencer, T.R., Sharp, E.L., Alonso, J.M., Ecker, J.R., and McClung, C.R.
(2003). Enhanced fitness conferred by naturally occurring variation in the
circadian clock. Science 302,
1049-1053.
SalomŽ,
P.A., and McClung, C.R. (2004). The
Arabidopsis thaliana clock. J.
Biol. Rhythms 19, 425-435.
SalomŽ,
P.A., and McClung, C.R. (2005a). What makes
Arabidopsis tick: Light and temperature entrainment of the circadian clock. Plant Cell Environ. 28, 21-38.
SalomŽ,
P.A., and McClung, C.R. (2005b). PRR7 and PRR9 are partially redundant genes essential for the temperature
responsiveness of the Arabidopsis circadian clock. Plant Cell
17, 791-803.
SalomŽ,
P.A., Xie, Q., and McClung, C.R.
(2008). Circadian timekeeping during early Arabidopsis
development. Plant Physiol. 147, 1110-1125.
updated October 22, 2008