Quantitative genetic variation and developmental clocks.

It is well-known that most genetic variation affects quantitative traits, and natural or artificial selection can act to change quantitative features of organisms more rapidly than qualitative ones. Surprisingly, variability is not confined to outbred species, but also occurs in inbred mice at a much higher rate than expected from known mutation rates. The size and shape of organisms and their constituent parts are, at least in part, controlled by the number of cell divisions, and there is published evidence for the existence of developmental clocks, which may count cell divisions. A molecular model for a developmental clock was previously proposed. It depends on the DNA methylation of repeated sequences of DNA, where the methylation of each additional sequence is tied to DNA synthesis and therefore cell division. The number of repeats specifies the number of divisions which will occur before a signal is produced which can activate or inactivate one or more genes. It is known that crossing over occurs between sister chromatids, and where tandemly repeated sequences occur unequal exchange can generate a larger or smaller number of repeats. An example of this is seen in the well-known variability of "minisatellite" sequences in human DNA. Unequal sister chromatid exchange can occur in mitotic and meiotic cells in the germ line, and in the case of developmental clock sequences could generate variation in clock length which in turn would directly affect quantitative traits. These events can be regarded as a special case of molecular drive during evolution.