Circadian Clock Properties and Their Relationships as a Function of Free-Running Period in Drosophila melanogaster

Abstract

The stability of circadian clock mechanisms under cyclic environments contributes to increased Darwinian fitness by accurately timing daily behavior and physiology. Earlier studies on biological clocks speculated that the timing of behavior and its accuracy are determined by the intrinsic period (τ) of the circadian clock under constant conditions, its stability, the period of the external cycle (T), and resetting of the clock by environmental time cues. However, most of these previous studies suffered from certain limitations, the major ones being a narrow range of examined τ values and a non-uniformity in the genetic background across the individuals tested. We present data that rigorously test the following hypotheses by employing Drosophila melanogaster fruit flies with τ ranging from 17 to 30 h in a uniform genetic background. We tested whether 1) precision (day-to-day stability of τ) is greater for clocks with τ close to 24 h; 2) accuracy (i.e., day-to-day stability of the phase relationship (ψ), where ψ is the duration between a phase of the rhythm and a phase of the external cycle) is greater for clocks with τ close to 24 h; 3) Ψ is delayed with an increase in τ; and 4) Ψ becomes more advanced with an increase in length of zeitgeber cycle (T). We show that precision is not always maximum for ~24-h clocks, but that accuracy is greatest when τ approximates T. Further, flies exhibit a delayed phase relationship with increasing τ and an advanced phase relationship under long T-cycles as compared with shorter T-cycles. We also describe relationships between activity and rest durations and how our observations fit predictions from models of circadian entrainment. Overall, we confirm that accuracy and phase of entrained rhythm are governed by both intrinsic clock period and the length of the external cycle; however, we find that the relationship between intrinsic period and precision does not fit previous predictions.

Heritable gene expression variability and stochasticity govern clonal heterogeneity in circadian period

“…Reports by Aschoff [ 37 ] as well as Pittendrigh and Daan [ 38 ] led the latter to hypothesize that circadian rhythms are most stable as the endogenous period (τ) approaches 24 h, whereas deviation of τ from 24 h leads to reduction in rhythm stability and provided an evolutionary reasoning for such a hypothesis. This observation of rhythm stability being the lowest at a particular τ has since been substantiated by studies on various species [ 39 , 41 , 42 ], including the pacemaker SCN neurons [ 40 ], but others have reported either weak or absence of such trends [ 52 , 53 ]. To assess whether such correlation is observed mostly at the level of organisms and central pacemaker neurons or is a general property even for peripheral oscillator cells, we measured the intercycle variation in period across our clonal populations.…”

Selection for Timing of Eclosion Results in Co-evolution of Temperature Responsiveness in Drosophila melanogaster

“…Additional factors that regulate Ψ ENT also include inter-oscillator coupling, amplitude of the zeitgeber and intrinsic amplitude of the circadian clock (Aschoff and Pohl, 1978; Bordyugov et al, 2015; Granada et al, 2013; Johnson et al, 2003; Roenneberg et al, 2010). While there are many studies that look at the effect of period on Ψ ENT in great detail (for instance, Rémi et al, 2010; Srivastava et al, 2019), there are relatively fewer experimental studies that have analyzed the effect of other factors such as zeitgeber strength and coupling on Ψ ENT (Abraham et al, 2010; Aschoff and Pohl, 1978). Moreover, each such study is performed on a different model system, and therefore, gaining a unifying understanding of clock features that regulate phasing and their inter-relationships is difficult.…”

Activity/rest rhythms of Drosophila populations selected for divergent eclosion timing under temperature cues

“…This response is characterised using a PRC (discussed above). Therefore, individuals with longer FRP are expected to show delayed phase under entrainment and vice versa, and this has found ample experimental evidence (Daan and Aschoff, 2001; Pittendrigh and Daan, 1976; Rémi et al, 2010; Roenneberg et al, 2005; Sharma et al, 1998; Srivastava et al, 2019; Wright et al, 2005). This however is thought to occur under the assumption that the PRC is a fixed entity in all these individuals.…”

“…Activity counts were then averaged across flies within each block to obtain population-wise profiles. As on multiple previous occasions (e.g., Nikhil et al, 2014; Srivastava et al, 2019), Centre of Mass (CoM) was used as a non-subjective phase marker ( ψ CoM ) so that changes in the waveform under different regimes are captured reliably. Owing to the bimodality of activity profiles under TC 12:12 and TC 18:06, an angle doubling transformation was performed before computing ψ CoM (Batschelet, 1981).…”