Principles and problems revolving around rhythm-related genetic variants.

Much of what is known about the regulation of circadian rhythms has stemmed from the induction, recognition, or manufacture of genetic variants. Such investigations have been especially salient in chronobiological analyses of Drosophila. Many starting points for elucidation of rhythmic processes operating in this insect entailed the isolation of mutants or the design of engineered gene modifications. Various features of the principles and practices associated with the genetic approach toward understanding clock functions, and chronobiologically related ones, are discussed from perspectives that are largely genetic as such, although intertwined with certain neurogenetic and molecular-genetic concerns when appropriate. Key themes in this treatment connect with the power and problems associated with multiply mutant forms of rhythm-related genes, with the opportunistic or problematical aspects of multigenic variants that are in play (sometimes surprisingly), and with a question as to how forceful chronogenetic inferences have been in terms of elucidating the mechanisms of circadian pacemaking.