Biological Rhythms in Drosophila melanogaster: Genetic Regulation, Adaptation, and Ecological Significance

Biorhythms are recurring physiological or behavioural events recognised in animals by the duration of time. In insects, ultradian (<20 h), circadian (20–28 h) and infradian (>28 h) rhythms have been studied. Ultradian rhythms show variations in periods (from milliseconds to hours), occur multiple times per day (thermoregulation, micturition, appetite, etc.) and also differ in functions and mechanisms (Lamont and Amir, 2017). Circadian rhythms are inevitable behavioural oscillations that a living organism evolves in its bid to synchronize with the temporal environment. Such oscillations (rhythmic patterns) as those that can take place with periods ranging across the different temporal scales are rather essential for survival (Forger, 2024). Infradian rhythms (> 24 h but less than a year) are influenced by photoperiod and hormonal changes. These rhythms fine-tune reproductive and metabolic functions over longer time scales. Biorhythms help fruit flies to optimize foraging, ensuring maximal energy intake while minimizing risks and energy expenditure (Koyama et al., 2020).

Circadian rhythms, which oscillate nearly 24 h, include the endocrine, sleep-wake, and feeding cycles. Circadian rhythms are regulated from inside the organism through homeostatic and exogenous components; zeitgeber (refers to environmental variables that are capable of acting as circadian time cues), for instance, light, temperature, and feeding, which help to synchronise the activities of organisms to match the change in the environment (Sharma and Chandrashekaran, 2005). The biological rhythms, if disrupted, impact negatively; these disruptions include genetic alterations, and environmental manipulations, disturbing survival, reproduction, and fitness of the organism (Amaral et al., 2014).

These rhythms run at various levels from biochemical and cellular to individual or population levels, with hierarchical subordinate oscillators that control vital processes including feeding, mating, migration, and predator evasion. For instance, diurnal insects plan their foraging at daytime since there are more openings during the day than nocturnal insects that target to forage at night, so that the chances of them being attacked by a predator are minimal by adjusting activity (Miyatake, 2011; Khyati et al., 2017). Weather cycles help insects and their pests to avert stress by entering a state of diapause. Moreover, biological rhythms regulate social activities within the colony in eusocial insects, including honeybees (Bashir et al., 2023). Additionally, these rhythms provide many opportunities to understand insect biology, given their applications in pest management and conservation (Khyati et al., 2017).

The reproductive success in an enhanced survival scenario in fruit flies, such as Drosophila, is accomplished by regulating energy expenditure and establishing metabolic controls in internally channelized oscillations of around 24 h called circadian rhythms. These rhythms regulate major tasks in daily life, such as motor control, eating and drinking, sex, and sleep. Biorhythms are controlled by a molecular clock located in brain cells and feedback-loop circuits working in a coordinating way with other clock genes (Beauchamp et al., 2018; Horn et al., 2019). These genes are involved in the regulation of proteins that fluctuate in concentration throughout the day, creating a cycle known as circadian rhythm (Helfrich-Förster, 2020; De and Chatterjee, 2021). Light is a zeitgeber in this case and sets forward or backwards the clock to the prevailing external environment at any one point in time (Beauchamp et al., 2018). Cytochrome (CRY) is a protein (Subramanian et al., 2016) that is necessary for perceiving the change in light and the changes within the body to match the circadian rhythm. Disruptions of these rhythms can undoubtedly lead to behavioural change and diminished viability of fruit flies and other animals exhibiting circadian rhythms (Wong et al., 2023; Córdoba et al., 2024).

Ultradian rhythm is an intracellular oscillator (cellular mechanism) that generates rhythmic activity within a cell. In contrast to circadian rhythms, which have a shorter period, this type of oscillator regulates the periodicity of energy intake and utilization by fruit flies (Horn et al., 2019). Ultradian rhythms are characterised by less than 24 hours of recurring activity that exists multiple times in the day, shaping some behaviours in D. melanogaster (De and Chatterjee, 2021). For example, feeding, grooming, and episodes of locomotor activity in D. melanogaster last for less than 24 hours (Seki and Tanimura, 2014). The efficiency of maintaining the behaviour of fruit flies is thus determined by environmental signals and needs (Pyża and Cymborowski, 2001; De et al., 2012). For example, shorter cycles of feeding patterns make the animal feed often, but it does not endanger itself through predation (Rhoades et al., 2018; Goh et al., 2019; Tang et al., 2022). Although ultradian oscillators are not explored as much as circadian rhythms (Goh et al., 2019). In D. melanogaster, ultradian rhythms are expressed as an oscillation of feeding and activity cycles during the day (Yee, 2014). These ultradian rhythms also have the further function of maintaining energy balance, or homeostasis (Yusuf et al., 2024). However, these are not involved in storing foodstuffs for longer periods, where they can avoid predators or bad environmental conditions (Schlichting and Helfrich-Foerster, 2015). Moreover, the grooming activity in fruit flies does not just occur with a circadian level, but an ultradian level, so the body senses and its cleanliness are always right on time (Thakurdas et al., 2010). Thus, such activities are governed by neural circuits and metabolic homeostatic feedbacks (Kühnlein, 2010; Kadow, 2019) which may act at least for the local and real physiological requirements (Frank, 2014; Gardner et al., 2016; Münch et al., 2020).

Drosophila melanogaster has long been recognized as an ideal model for studying biological rhythms due to its short life cycle, genetic tractability, and fully sequenced genome. Like many other animals, its behaviours, such as movement, feeding, and reproduction, are regulated by internal biological clocks. Foundational genes involved in these rhythms include clock (clk), cycle (cyc), period (per), and timeless (tim) (Tataroglu and Emery, 2014; De and Chatterjee, 2021). The experimental evidence from studies on biological rhythms, such as circadian and ultradian rhythms, can be used to relate other animal groups, including vertebrates. These genes work together in interconnected feedback loops to maintain rhythmic activity (Zordan and Sandrelli, 2015). Variations in the photoperiod and temperature influence these rhythms both positively and negatively, which ultimately regulate energy expenditure. Metabolic controls in fruit flies help them to become well established in their ecological niches. per and tim genes are transcribed at night, both to degrade proteins (PER and TIM). Whereas at daytime, PER and TIM proteins are transcribed (De and Chatterjee, 2021). At a higher concentration of PER and TIM proteins, they can form complexes as they are retained in the cytoplasm, but can cycle back to the nucleus. The direct down-regulation of transcription by binding to CLK and CYC proteins occurs (Tataroglu and Emery, 2015). These loops of negative feedback result in cyclic changes in PER and TIM that enable the temporal organization of behaviour and physiologic processes to recur daily (Meyer et al., 2006; Tataroglu and Emery, 2015). Light is processed through the Cryptochrome (CRY), which is light responsive and through this influences the degradation of TIM to reset the clock (Meyer et al., 2006). This molecular mechanism ensures feeding and movement activity of fruit flies is governed by the circadian rhythm (Goto and Denlinger, 2002). Temperature and light cycles, known as zeitgebers, help align internal rhythms with the external world, ensuring energy-efficient behaviour. This coordination allows fruit flies to optimize survival and reproduction in their ecological niches. The role of epigenetic regulation, such as DNA methylation and histone modifications, in fine-tuning the expression of clock genes is also crucial in biorhythms. These changes, which can be triggered by environmental factors, may influence the strength or timing of rhythmic behaviours and can sometimes even be inherited across generations (Gibert and Peronnet, 2021).

Feedback loops are core regulatory circuits that fine-tune gene activity. Positive loops amplify transcription, whereas negative loops dampen it, together safeguarding cellular homeostasis. In Drosophila, PER and TIM proteins first accumulate in the cytoplasm; once they reach a threshold, they form complexes that relocate to the nucleus (Saez and Young, 1996). There, the complexes bind to and silence the CLK/CYC transcription factors, blocking the phosphorylation events required to restart per and tim transcription (Taylor and Hardin, 2008). As daylight promotes PER and TIM degradation, the inhibition lifts and the cycle recommences, producing a ~24 h rhythm that can synchronize with light and temperature cues (Sidote et al., 1998; Patke et al., 2020).

Beyond these protein feedback loops, epigenetic layers add another level of time control (Hardin, 2011). DNA methylation and histone modifications can modulate core-clock gene expression and adjust circadian amplitude (Libbrecht et al., 2020). Such epigenetic marks may be inherited or triggered by external factors, occasionally pushing the clock out of synchronisation. Environmental signals like light, temperature, and food availability act as zeitgebers that align internal rhythms with the outside world (Stevenson, 2018; Wu et al., 2024). Together, protein feedback and epigenetic tuning ensure the circadian system stays flexible under changing conditions (Qureshi and Mehler, 2014; Jarabo and Martin, 2017; Faragó, 2021).

Zeitgebers refer to environmental cues that are required to entrain or synchronise biological rhythms (Beer et al., 2019; Quante et al., 2019). These environmental cues (such as light, temperature, etc.) provide input to the circadian clock (Quante et al., 2019), which are significant in time keeping in fruit flies (De and Chatterjee, 2021). Such cues help the flies maintain coordination between the internal biological clock and the environmental conditions in order to enhance their living and physiological standards (Horn et al., 2019). Light is an external stimulus or zeitgeber because, in addition to other roles that it plays, it also controls the number of clock genes and synchronizes the circadian cycle with photoperiod. Cryptochrome (CRY), a photoprotein, detects light and directs the ubiquitination of the TIM protein to govern the daily entrainment (Helfrich-Förster, 2020; Cong et al., 2023). Temperature is another factor that triggers the circadian cycle when coordinated with light cycles (Cavieres et al., 2018; Fiaboe et al., 2021). The oscillatory activity and clock genes are sensitive to temperature fluctuations (Fiaboe et al., 2021). In particular, the whole biological rhythm oscillates at a higher frequency in fruit flies at higher temperatures and at a slower rate at lower temperatures. Thus, providing them with a mechanism of adaptation to different temperature regimes (Amin et al., 2019; Choudhary et al., 2019; Huang et al., 2020). The availability of resources determines the feeding and overall activity (Cavieres et al., 2018; Fiaboe et al., 2021; Yu et al., 2022). For example, the fruit flies adjust the hours of activity or food intake, taking into consideration the foods, so that the ones consuming energy are high when the predators are least around. Together, these stimuli enable fruit flies to regulate activity and metabolic rates in response to cyclical changes in the environment to optimize chances of survival and propagation (Amin et al., 2019; Huang et al., 2020).

Fluctuations in photoperiod and temperature play a critical role in modulating biological rhythms in D. melanogaster, ultimately influencing energy expenditure and metabolic efficiency (Dubowy and Sehgal, 2017). These rhythms enable fruit flies to fine-tune their physiological processes to match environmental conditions, ensuring better adaptation and survival within their ecological niches. Circannual rhythms, for instance, allow fruit flies to perceive and respond to seasonal changes in photoperiod and temperature, factors essential for synchronising key biological processes like reproduction and diapause. Light is detected through the photoreceptor CRY protein, which influences the degradation of TIM protein and thereby resets the circadian clock (Meyer et al., 2006). This molecular feedback mechanism ensures that feeding and locomotor activity are tightly regulated in alignment with the day–night cycle (Goto and Denlinger, 2002).

External cues known as zeitgebers (such as light, temperature, and food availability) play a central role in entraining or synchronising internal biorhythms to environmental cycles (Mistlberger and Rusak, 2021). Light, for example, entrains the circadian rhythm by modulating gene expression through CRY-mediated degradation of TIM, affecting behaviours such as sleep, foraging, and metabolism (Schlichting et al., 2019). Temperature, when acting in concert with photoperiod, also serves as a potent entrainment cue. Clock genes exhibit sensitivity to thermal fluctuations, with circadian rhythms typically accelerating at higher temperatures and decelerating in cooler conditions. Moreover, the availability of food resources functions as a behavioural cue that influences both feeding and activity patterns (Krittika and Yadav, 2020). Fruit flies often adjust their foraging schedules based on resource abundance and predator avoidance strategies (Drew and Yuval, 1999). These combined environmental signals help to optimize metabolic rate and behavioural activity, ultimately enhancing survival and reproductive success across changing conditions.

The oscillations in the metabolic rate also impact population dynamics since the fruit flies can go through low temperatures or scarcity of food during times of unsuitable climate (Dos Santos and Cochemé, 2024; Fangninou et al., 2024). Thus, fruit flies can overcome definite population minima and are capable of maintaining constant population density within the seasons (Hui, 2024; Thoré et al., 2024; Vivekanandhan et al., 2024). Disturbance of rhythms in fruit flies (such as Drosophila melanogaster) poses several challenges and survival risks (Fangninou et al., 2024). This is because behaviour and physiology, both oscillators, are decoupled from the environment, as measures and programs are out of alignment (Pham et al., 2024; Vivekanandhan et al., 2024). Disruptions of the circadian rhythm create problems in feeding and reproductive activity.

Biorhythms, through precise synchronisation with environmental cues, are crucial in maintaining physiological balance, enhancing survival, and ensuring reproductive success. The genetic regulation of these rhythms, particularly circadian, ultradian, and infradian, demonstrates how molecular feedback loops allow fruit flies to adapt to daily, short-term, and seasonal changes. The study of these biological rhythms not only offers insights into fundamental chronobiological processes but also holds practical value in pest management by identifying optimal timings for control strategies. Ultimately, understanding the rhythmic behaviour of Drosophila enhances our knowledge of ecological adaptation, evolutionary fitness, and the broader implications of biological timing in insects.

The authors greatly acknowledge the intellectual input of MPhil Scholars of the Systematics and Pest Management Lab during the discussion and finalisation of this article.

This review uniquely synthesizes the molecular and epigenetic regulation of circadian rhythms in Drosophila melanogaster. It highlights how classical feedback loops involving PER, TIM, CLK, and CYC are genetically conserved. The biorhythms are also dynamically modulated by epigenetic mechanisms such as DNA methylation and histone modifications.

SK and MH conceived the idea and prepared the original draft.

AI and MH critically reviewed and revised the manuscript.

The authors have declared no conflict of interest.