Nature is filled with processes that maintain an ordered state. Perhaps you have seen magnetic toys that keep an object suspended in the center of a space, such that any slight movement makes it snap back into position. Gravity keeps planets in orbits, and compresses stars into spheres. The gyroscopic effect keeps a bicyclist upright. Sand dunes maintain their shape due to the angle of repose of piled sand grains. Centripetal force keeps hurricanes and tornadoes circling around a center. The Coriolis effect maintains wind patterns. These familiar examples can be explained with reference to natural laws.
There’s a different kind of maintenance in biology, called homeostasis. It is the subject of biologist Scott Turner book, Purpose and Desire: What Makes Something “Alive” and Why Modern Darwinism Has Failed to Explain It. This kind of “dynamic equilibrium” is maintained by machinery acting on other machinery. No natural law can maintain that kind of order. Indeed, natural laws would lead to decay and death if it were not for programmed responses able to overcome what would happen naturally. Here are some examples of that kind of active maintenance.
Sleep On It
Why is sleep necessary? A new theory by Zada et al. published in Nature Communications (open access) proposes that the body needs a night shift to allow repair crews time to work. According to an open-access commentary on this paper in Current Biology by Philippe and Wang, “sleep can repair DNA breaks accumulated during wake to maintain genome integrity and likely slow down neuronal aging.”
Energetic daytime activities are costly. The buzz of activity in the nucleus, with frequent unwinding and untangling of DNA as genes are read and transcribed, can cause genetic disruptions. Among the most dangerous are double-stranded breaks (DSB), which can lead to cell death or cancer. DSB repair systems require snatching both ends of loose strands and stitching them back together — a complex process by molecular machines designed for this kind of emergency. Experiments on zebrafish brains showed that DSB repair genes were up-regulated during sleep.
Altogether, the common observations of wake-dependent DSBs and sleep-dependent DSB repair in flies, mice and zebrafish point towards an exciting core function of sleep that could be critical in understanding a diverse range of biology from cellular aging to neural degeneration. For too long, the sleep field has been dominated by system-level descriptions of phenomenology that does not reflect the full biological underpinnings of this critical state. The discovery of sleep functions at the subcellular level finally focuses the need to understand and define sleep at the cellular level. [Emphasis added.]
Without the repair crew actively working to maintain our brains each night, toxic substances could accumulate. A paper in The Journal of Neuroscience links poor-quality sleep to Alzheimer’s disease. Winer et al. say that subjects with a decreasing quantity of sleep in their 50s to 70s tend to have accumulations of β-amyloid and tau proteins that are diagnostic of the disease (read the summary at Science Daily). Perhaps this is due to the lack of time for the night shift maintenance crew to work. Zada et al. had shown that the effects were related to sleep length, not the circadian clock, so lack of sleep can be harmful whether one is a night owl or an early riser. Philippe and Wang explain why we cannot be awake all the time.
The intuitive idea of sleep being a restorative phase should of course be strange to no one, but the accumulation of tangible molecular or subcellular evidence scientifically illustrating such a role is actually fairly recent. The neuronal activity of the brain during wake comes at a cost. As one explores and learns, new connections are created and synaptic strength increases in many regions of the brain, a dynamic that cannot be sustained indefinitely. Thus, one of the first hypothesized functions for sleep is to ensure synaptic homeostasis. Correlated to this increased synaptic activity during wake is the production and accumulation of waste and proteins such as beta amyloid (Aβ), and sleep is likely an important period during which major toxic metabolites are cleared from the brain including Aβ.
Photosynthesis: Stability Under Stress
Plants are at the mercy of the sun. They can’t move, but the amount of sunlight is constantly changing. Too much light can overpower the photocenters in their chloroplasts, resulting in reactive oxygen species (ROS) — molecules that can damage cells. At night, there is too little light, but excess electrons must be handled as the light level rises in the morning. Two recent papers tell how plant machines maintain homeostasis under these conditions. Saroussi et al., writing in PNAS, explore “Alternative outlets for sustaining photosynthetic electron transport during dark-to-light transitions.”
Most forms of life on Earth cannot exist without photosynthesis. Our food and atmosphere depend on it. To obtain high photosynthetic yields, light energy must be efficiently coupled to the fixation of CO2 into organic molecules. Suboptimal environmental conditions can severely impact the conversion of light energy to biomass and lead to reactive oxygen production, which in turn can cause cellular damage and loss of productivity. Hence, plants, algae, and photosynthetic bacteria have evolved a network of alternative outlets to sustain the flow of photosynthetically derived electrons.
The authors describe three mechanisms plants use to manage the flow of excess electrons at different times of the day. One involves using specific proteins to convert O2 to H2O. Another involves PTOX (plastid terminal oxidases) that capture excess electrons during the electron transfer chain (the sequence of machines that generates the proton motive force for ATP synthase). “It was previously demonstrated that PTOX controls the redox state of the PQ [plastoquinone] pool in the dark and may act as a safety valve during periods of environmental stress.” The third mechanism shuttles excess electrons to machines that synthesize starch. Suffice it to say that plants have multiple crews at the ready to protect themselves from too much or too little sunlight.
Plants are susceptible to stress, and with the global impact of climate change and humanity’s growing demand for food, it’s crucial to understand what causes plant stress and stress tolerance. When plants absorb excess light energy during photosynthesis, reactive oxygen species are produced, potentially causing oxidative stress that damages important structures. Plants can suppress the production of reactive oxygen species by oxidizing P700 (the reaction center chlorophyll in photosystem I). A new study has revealed more about this vital process: the cyclic electron flow induced by P700 oxidation is an electric charge recombination occurring in photosystem I.
The way these systems shuttle electrons around to prevent overheating and prevent ROS from causing damage brings to mind human factory safeguards. A well-designed power plant will have escape valves, procedures and machinery to prevent overheating. A well-designed explosives factory will have multiple regulations and safeguards to handle delicate substances. With plants, these safeguards come built-in.
Yeast Translation Coordination
One final example concerns the lowly one-celled eukaryote, yeast. Researchers at the University of Göttingen learned more about how yeast cells protect themselves from short proteins.
The cell contains transcripts of the genetic material, which migrate from the cell nucleus to another part of the cell. This movement protects the genetic transcripts from the recruitment of “spliceosomes”. If this protection does not happen, the entire cell is in danger: meaning that cancer and neurodegenerative diseases can develop.
In most eukaryotic cells, messenger RNAs transcribed from DNA are first spliced by the spliceosome, which cuts out introns and stitches exons together before the mRNAs are sent outside the nucleus to the ribosomes for translation. Parts of the spliceosome, called snRNA (small nuclear RNA) also leave the nucleus along with the messenger RNA, but the snRNAs are not translated into protein. Scientists had thought yeast were different. They thought the snRNA of yeast never left the nucleus. The team learned that in fact they do go into the cytosol to become matured before returning to the nucleus. Why is this important? If the snRNA remained in the nucleus, the spliceosomes would try to work with them, but they would not be ready.
“This is the reason that healthy cells must first send the precursors of messenger RNA out of the cell nucleus immediately after their production: it is to prevent them from being used by the developing spliceosomes. This basic understanding is important in order to identify the underlying cause of the development of diseases.”
We learn from their paper in Cell Reports that multiple proteins are involved in this shuttling process, and that “snRNA export prevents an incorporation of immature snRNAs into spliceosomes.” If they don’t make it out in time, bad things can happen: “Spliceosomal assembly with immature snRNAs results in genome-wide splicing defects.” That’s what they found when they interfered with the shuttle operation. They say “Importantly,” twice about this:
Importantly, all three situations in which the pre-snRNAs were brought into contact with the spliceosome, this molecular machine incorporated these immature snRNPs, revealing that the spliceosome cannot distinguish between immature and mature snRNAs. Importantly, all “immature” and thus faulty spliceosomes lead to splicing defects. From these data, we suggest that snRNA shuttling is probably obligatory for all eukaryotes and for all snRNAs, including U6, because it represents a quality assurance mechanism for intact spliceosomes.
The spliceosome, by the way, is one of the largest and most complex molecular machines in the cell. Here we see that it is assisted by other machines.
Examples like these can be multiplied by thousands: living machines helped by other machines to maintain homeostasis. These are very unlike non-living processes that can maintain order according to natural law. These actually counteract what would happen naturally. Just like human engineers build machines that can do what blind natural laws would never do on their own, like lift tons of metal machinery through the air, fly it around a continent and land it gently on the ground, living things work their “miracles” (like photosynthesis) by means of highly engineered devices. And beyond that, these devices are kept in dynamic equilibrium by other devices that know how to handle stresses and anomalies. This is surely wondrous!