Clock, molecular

In the 1960, it was noticed that substitutions in some amino acid sequences seemed to occur at a roughly constant rate over time (Zuckerkandl and Pauling, 1965). This is the well known molecular clock hypothesis. For a particular protein such as cytochrome c or myoglobin, it was noticed that there was a linear relationship between divergences of pairs of sequences, as measured by numbers of amino acid differences, and divergences of the species, as measured by dates from the fossil record. There is still considerable debate as to how accurate the molecular clock may be and as to how it might vary systematically depending on the species, type of protein, and kinds of substitutions that are counted. 

Felsenstein, J. (1985b). Confidence limits on phylogenies with a molecular clock. Syst. Zool. 34, 152-161. 

The mutation rate fx of the nucleotide (or amino acid) at a sequence site is related to the popular notion of a molecular clock (Zuckerkandl and Pauling, 1965), because it determines after which time the clock ticks and anew mutation arises because of a copying error during meiosis. Whether this clock ticks uniformly is a topic of prolonged debate (summarized in Li, 1997). The question is usually treated by comparing sequence difference at (supposedly) neutral sites with evolutionary distance between species. 

Pahneirim, D. Henrique, D. Ish-Horowicz, and O. Pourquie, Avian hairy gene expression identifies a molecular clock linked to vertebrate segmentation and somitogenesis. Cell 91, 639-648 (1997). 

M. Maroto and O. Pourquie, A molecular clock involved in somite segmentation. Curr. Top. Dev. Biol. 51, 221-248 (2001). 

Molecular clocks and light signalling. Wiley, Chichester (Novartis Foundation Symposium 253)p 3-30... 

Even though the studies on ROREs within the Dhp promoter did not teach us much about Dbp transcription, we did uncover an important function of circadian REV-ERBa accumulation this repressor governs the cyclic transcription of Bmal1 and Clock, two central components of the molecular clock (Preitner et al 2002). 

Bonnefont X, Albus H, Meijer JH, van der Horst GTJ 2003 Light signalling in Crjptochrome-deficient mice. In Molecular clocks and light signalling, Wiley, Chichester (Novartis Found Symp 253) p 56—72... 

Bunney WE, Bunney BG 2000 Molecular clock genes in man and lower animals possible impHcations for circadian abnormahties in depression. Neuropsychopharmacology 22 335-345... 

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