Eco-crossover, or environmentally regulated crossing-over, and natural selection are two irreplaceable drivers of adaptive evolution: Eco-crossover hypothesis.

The existence of an environmentally regulated version of meiotic crossing-over, or eco-crossover, is proposed, and the main consequences of this hypothesis are considered. Eco-crossover is a key source of partially directed genetic diversity of eukaryotes. In stressful environment, it creates ecologically justified and topologically specific genetic changes, and hence phenotypic variability, with which the selection works. If variability were random, then, in the face of rapid environmental changes, natural selection could not create life-saving adaptations in a timely manner. Owing to the eco-crossover activity, epimutations, i.e., eco-dependently marked chromosomal sites, are transforming into mutations. In its work, eco-crossover uses the eco-stress-dependent versions of circular RNAs ("ecological" circRNAs), which, against the background of eco-stresses, are synthesized as variants of alternative splicing. These ecological circRNAs, binding to homologous epimutations on the homologous parent chromosomes of the meiocyte, involve them in topologically specific recombinations. These recombinations can create random mutations in nonrandom genomic sites. These quasi-random mutations serve as a pivotal source for creating all adaptations of any level of complexity. The drivers of the adaptive evolution of eukaryotes, both in micro- and macroevolution, are two irreplaceable factors - eco-crossover and natural selection.

Planetary Metronome as a Regulator of Lifespan and Aging Rate: The Metronomic Hypothesis.

A metronomic mechanism for the duration control of ontogenetic cycle periods of an animal is proposed. The components of the proposed metronomic system include the ventricular system of the brain, planet Earth as a generator of metronomic signals, and temporal DNA (tDNA) as a substrate that is epigenetically marked to measure elapsed time of ontogenesis. The metronomic system generates repetitive signals in the form of hydrodynamic disturbances in the cerebrospinal fluid (CSF). The metronomic effect arises due to the superposition of two processes - the near-wall unidirectional flow of CSF and oscillations in the movement of the planet. Hydrodynamic impacts of the metronome are transformed into nerve impulses that initiate epigenetic modification of tDNA in neurons, changing the content of factors expressed by this DNA for innervated targets of the body. The duration of ontogenetic cycle periods, including duration of the adult life, depends on the rate of addition of epigenetic marks to tDNA. This rate depends mainly on the frequency of the metronomic signals used by each particular species. But epigenetic modifications can also be influenced by factors that modulate metabolism and the rate of chromatin modifications, such as a calorie-restricted diet.

Role of the Earth's Motions in Plant Orientation - Planetary Mechanism.

According to the proposed theory, the starch-rich particles (statoliths) help the plant to convert the signals from Earth's motions into the signals necessary for the plant to perceive its orientation relative to the gravity vector while moving freely because of inertia in the sensory cells (statocytes) of roots and stems. Motions of the Earth are never constant, which, in particular, refers to the so-called polar motions and oscillations of the planet's rotation axis. Statoliths at any given moment move in the cytoplasmic liquid of statocytes due to inertial motion initiated by the action of the Earth's movements, maintaining the trajectory set by the previous movement of the oscillating planet. Unlike statoliths, the walls of a statocyte move in space along with the entire plant and with the Earth, in strict accordance with the current direction of motion of the planet's axis. This leads to the inevitable collision of statoliths with the statocytic wall/membrane. Cytoplasmic liquid, as a substance that is not able to maintain its shape, does not interfere with the inertial motions of the statoliths and collision with the wall of the statocyte. By striking the membrane, statoliths cause the release of ions and other factors at the impact site, which further participate in the gravitropic process. Pressure of the sediment of statoliths at the bottom of the statocyte, as well as position of this sediment, are not the defining factors of gravitropism.

Interstitial telomeric repeats-associated DNA breaks.

During a cell's lifespan, DNA break formation is a common event, associated with many processes, from replication to apoptosis. Most of DNA breaks are readily repaired, but some are meant to persist in time, such as the chromosome ends, protected by telomeres. Besides them, eukaryotic genomes comprise shorter stretches of interstitial telomeric repeats. We assumed that the latter may also be associated with the formation of DNA breaks meant to persist in time. In zebrafish and mouse embryos, cells containing numerous breakage foci were identified. These breaks were not associated with apoptosis or replication, nor did they seem to activate DNA damage response machinery. Unlike short-living, accidental sparse breaks, the ones we found seem to be closely associated, forming discrete break foci. A PCR-based method was developed, allowing specific amplification of DNA regions located between inverted telomeric repeats associated with breaks. The cloning and sequencing of such DNA fragments were found to denote some specificity in their distribution for different tissue types and development stages.

Chronographic theory of development, aging, and origin of cancer: role of chronomeres and printomeres.

It is supposed that the development and aging of multicellular animals and humans are controlled by a special form of the clock mechanism - a chronograph. The development of animals and their aging are interconnected by the program of the species lifespan that has been selected in the evolution of each species to fit the resources of its ecological niche. The theory is based on the idea about a controlled loss by the neurons in the brain of hypothetical organelles - chronomeres that represent themselves small DNA molecules, which are amplificates of the segments of chromosomal DNA. A regular mode of the process of chronomere losses by neurons is provided by a pacemaker localized in the pineal gland and activated at least once per lunar month. Neurons, consecutively losing their chronomeres, are organized in the brain in the temporal relay race. Analogues of chronomeres, namely printomeres, are supposed to exist in dividing non-neuronal cells. Printomeres are not involved in a performance of temporal function, instead they are responsible for the maintenance in dividing cells of their memory about the state of differentiation. A critical shortening or loss of a printomere in a dividing cell leads to a cellular senescence, whereas telomere shortening is a bystander of this process. Thus, aging of a multicellular organism is associated with the loss of chronomeres, whereas senescence of dividing cells is associated with the loss of regulatory RNAs encoded by printomeres. If the cells that have lost their printomeres are environmentally forced to divide, they can transform into cancer cells.

Chronographic Theory of Development, Aging, and Origin of Cancer: Role of Chronomeres and Printomeres.

It is supposed that the development and aging of multicellular animals and humans are controlled by a special form of the clock mechanism - a chronograph. The development of animals and their aging are interconnected by the program of the species lifespan that has been selected in the evolution of each species to fit the resources of its ecological niche. The theory is based on the idea about a controlled loss by the neurons in the brain of hypothetical organelles - chronomeres that represent themselves small DNA molecules, which are amplificates of the segments of chromosomal DNA. A regular mode of the process of chronomere losses by neurons is provided by a pacemaker localized in the pineal gland and activated at least once per lunar month. Neurons, consecutively losing their chronomeres, are organized in the brain in the temporal relay race. Analogues of chronomeres, namely printomeres, are supposed to exist in dividing non-neuronal cells. Printomeres are not involved in a performance of temporal function, instead they are responsible for the maintenance in dividing cells of their memory about the state of differentiation. A critical shortening or loss of a printomere in a dividing cell leads to a cellular senescence, whereas telomere shortening is a bystander of this process. Thus, aging of a multicellular organism is associated with the loss of chronomeres, whereas senescence of dividing cells is associated with the loss of regulatory RNAs encoded by printomeres. If the cells that have lost their printomeres are environmentally forced to divide, they can transform into cancer cells.

Lunasensor, infradian rhythms, telomeres, and the chronomere program of aging.

According to the redusome hypothesis, the aging of an organism is determined by the shortening of chronomeres (small perichromosomal linear DNA molecules). In this paper, a presumptive role for infradian hormonal rhythms is considered. Endogenous infradian rhythms are supposed to actively interact with those hormonal shifts which are governed by an exogenous infradian gravitational lunar rhythm. As a result of this interaction, the so-called T-rhythm is formed. Peaks of T-rhythms are used as the pacemaker signals to keep the life-long "clockwork" of the brain running. The "ticking" of this clock is realized by the periodically repeated shortening of chronomeres in postmitotic neuroendocrine cells, which occurs just at the maxima of T-rhythms. Shortening of telomeres in mitotic cells in vivo is a witness of the aging of the organism, but not the cause of aging. The primary cause of aging is shortening of chronomeres, the material carriers of a temporal program of development and aging. To recognize exogenous gravitational infradian rhythms, a special physiological system--the "lunasensor" system--evolved. It is assumed that it is a necessity to have a lunasensor as a particular variant of sensors of gravitation.