Significant fraction (98.5% in humans) of most animal genomes is non- coding dark matter. Its largely unknown function (1-5) is related to programming (rather than to spontaneous mutations) of accurate adaptation to rapidly changing environment. Programmed adaptation to the same universal law for non-competing animals from anaerobic yeast to human is revealed in the study of their extensively quantified mortality (6-21). Adaptation of animals with removed non-coding DNA fractions may specify their contribution to genomic programming. Emergence of new adaptation programs and their (non-Mendelian) heredity may be studied in antibiotic mini-extinctions (22-24). On a large evolutionary scale rapid universal adaptation was vital for survival, and evolved, in otherwise lethal for diverse species major mass extinctions (25-28). Evolutionary and experimental data corroborate these conclusions (6-21, 29-32). Universal law implies certain biological universality of diverse species, thus quantifies applicability of animal models to humans). Genomic adaptation programming calls for unusual approach to its study and implies unanticipated perspectives, in particular, directed biological changes.
Deep Dive into Non-coding DNA programs express adaptation and its universal law.
Significant fraction (98.5% in humans) of most animal genomes is non- coding dark matter. Its largely unknown function (1-5) is related to programming (rather than to spontaneous mutations) of accurate adaptation to rapidly changing environment. Programmed adaptation to the same universal law for non-competing animals from anaerobic yeast to human is revealed in the study of their extensively quantified mortality (6-21). Adaptation of animals with removed non-coding DNA fractions may specify their contribution to genomic programming. Emergence of new adaptation programs and their (non-Mendelian) heredity may be studied in antibiotic mini-extinctions (22-24). On a large evolutionary scale rapid universal adaptation was vital for survival, and evolved, in otherwise lethal for diverse species major mass extinctions (25-28). Evolutionary and experimental data corroborate these conclusions (6-21, 29-32). Universal law implies certain biological universality of diverse species, thus quantifi
Unusual approach to genomics (via analysis of readily available mortality data) unravels unanticipated function of non-coding DNA.
Mendel study of hereditary traits, later related to few alleles, revealed units of heredity.
Such traits are rare, and Mendel laws were disregarded until rediscovered. Arguably, similar bias in mortality studies significantly delayed discovery of non-genetic heredity.
In 1825 Gompertz (33) started ongoing search (34)(35)(36)(37)(38) for the law of universal mortality.
Mortality of evolutionary unprecedented human and laboratory animals, which are mostly protected (further protected populations) from competition with other animals, is extensively quantified. Their mean lifespan (immature stages including) exhibits extraordinary phylogenetic irregularity (6-21). Immature nymph stage in mayfly and cicada Magicicada is up to 4 and 23 times longer than embryo stage in humans, 100 and 1,700 times longer than larvae stage in Drosophilae. Mature Mean Lifespan (MLS) is about 1-2 days in single cell yeast -and mayfly whose adults do not eat, rapidly senesce and die after mating; 20-50 days in nematode -and Drosophilae. MLS of human is closer to hydra with no signs of aging for 4 years, and possibly immortal (39), than to mice with MLS~1 year. From mayfly to humans, MLS increases ~30,000 times, the ratio of immature to mature time decreases more than 100,000 times. Certain mutations change MLS in mice 1.6-fold (8), and in nematode 3.6 times (17).
Human MLS significantly and irregularly changes with calendar year. For instance, female MLS (calculated according to mortalities at different ages in a given calendar year-further only such data are considered) in Sweden was 18.8; 41.4; 28.9; 47.3 years in 1773; 1774; 1809; 1823 correspondingly. Mortality depends on genotypes, phenotypes and their heterogeneity, environment, living conditions and their change, life histories, etc-see, e.g., entire issue of Cell 120, #4 (2005). The Gompertz law did not quantify all these factors, was often very inaccurate, thus disregarded in all theories of aging and mortality (40). To estimate and forecast human mortality, demographers developed over 15 different approximations (41). The lifespan of four populations of inbred 3X3 male drosophilae in presumably identical shell vials varied from 18.6 to 34.3 days (9). Thus, living conditions, which look as micro-environmental variations, may in fact be very different and age dependent.
However, raw data demonstrate that when a single number relates age of a given species to human age, then under certain conditions survivability dependence on such scaled age and MLS is predominantly the same for different populations of species as diverse as anaerobic and aerobic yeast, nematode, mayfly, drosophilae, mouse, and human. Such invariance to all other factors is sufficiently restrictive to yield the variables, exact formula, and conditions of validity of the universal mortality law (which in special cases reduces to the set of Gompertz laws) in a general case. The law is verified with all available data; deviations from the law quantify living conditions of a given populations and species. In rapidly changing environment, mortality accurately adjusts to the law. Universality of the law and adjustment to it in diverse species, as well as over two centuries of human data, proves that such law and the possibility of such adjustment are hereditary. Thus, while such adjustment is acquired and rapidly reversible, its universality is provided by unusual express adaptation. Hereditary exact law and express adaptation to it must be programmed (rather than related to specific coding genes and slow spontaneous mutations) by noncoding DNA.
For the sake of biologists, all formulas are shifted to the last section
In mature stage probability to survive to the age x, as well as MLS e for each species, sex and population (country and calendar year of birth and death for humans) are listed in readily available life tables (6-21). Figure 1a 42), e=21.6 generations], mayfly (11), drosophilae (10), mouse (8), correspondingly e=1.6, 36, 714 days. The shapes of human curves with e ≈ 64, 42, 32, 20 years, are very different, yet close for close values of their e. Scale “biological time” of different species according to the values of e in their close curves. This equates 1 generation of anaerobic and aerobic yeast; 1 day of nematode, mayfly, drosophilae and mouse to correspondingly F=5.5 and 4; 2.4, 50.7, 1.8, 0.17 human years. For their different populations Fig. 1b manifests predominantly universal survivability (X, E) to any scaled age X= Fx for the scaled mean lifespans (SLS) E= Fe 20,32,42,64,83,130, 295 (here and on X and E in years). Mortality is stochastic, thus significant fluctuations in survival curves of small animal populations [21, 26 mice (8); 48 (12), 68, 39 (17) nematodes; yeast 16,15,14 anaerobic (20) and 35, 46, 45 aerobic (42, 15, 16) initial yeast cells; at, e.g.
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