1 Evolution is the description of all evolution, and life is its concrete expression, that is, a dynamic equilibrium. Our life is a multi-level equilibrium, just like the various relationships in nature that are ultimately at the bottom of the relatively stable proportions of each species.

2 The essence of evolution is the process of change from simple to complex, from non-living matter to life, and species are also changeable, essentially the mutation of intrinsic genes, and then there are specific individuals who stand out in the screening of the environment, and finally be able to reproduce, and finally form reproductive isolation that marks the formation of species. This pattern is also reflected in the evolution within living organisms. The evolution at the molecular level is neutral, but there is a certain bias in the continuous transition of the hierarchy to the biological organism level. This idea is an application of the infinitesimal quantities of calculus.

3 Lamarck's evolutionary thought, long-term evolutionary development and formation of species; Changes in the environment/changes in needs lead to changes in biological behavior, and epigenetics can theoretically penetrate down to the genetic level and thus affect higher levels such as the morphology of the organism. Lamarck's view may exist at this molecular level, which is certainly one of the basic assumptions of various biological sciences. Now the treatment of various factors and the measurement of the final indicators: one uses the genes that are constantly used are strengthened, and the other is weakened, which is the expression at the gene level; Rather, it is the inheritance of acquired traits, that is, it may have a certain continuity, but at the lower level, such as the cellular/molecular level, the organism level requires a wider interval to achieve it.

4 Darwin's Thought: Natural Selection, Survival of the Fittest. A mutation provides infinite possibilities, that is, a traversal of all possible paths, and finally a certain degree of adaptability can be derived according to the interaction with the environment; the second is the competition for survival, which is like the interference of waves, and finally can form a certain collapse path; 3 Natural selection, survival of the fittest, can pass on favorable mutations. 4 sexual selection, a kind of compensation, is able to be screened through a variety of mechanisms. This is an equilibrium achieved by a multi-level competitive game. 5 The Tree of Life, the macroscopic trajectory of evolution, which is a fractal structure.

5 Excavation of the genetic basis of biological evolution, that is, genes at the molecular level, which is a fixed point of explanation, through which changes at the macroscopic level can be explained. On this basis, we are able to introduce various biological processes through the combination of genes and so on. The lack of transition types of species may be like a quantum level transition, which is a similarity of levels; And the special itself is not special at all, but more special is dead; The formation of complex structures is actually a kind of historical inertia, the result of gradual mutation and accumulation.

6 Mendel's hybridization experiments with the laws of segregation and independent assignment are based on experimental discoveries, and then the concept of genetic factors can be abstracted and the genes can be found in the DNA sequence to correspond. This is based on the results of data analysis, i.e., various population genetics. Like epidemiological studies.

7 Hada-Weinberg equilibrium, in a large population without mutation/natural selection/migration, random mating (ideal hypothesis), gene frequencies and genotype frequencies meet q?:2qp:p? (A:q; a:q), this theorem can actually be represented by the Markov process of stochastic processes, where the gene frequency is the high-dimensional probability matrix, and the genotype frequency is its specific expression, if it satisfies q?:2qp:p?, it can be regarded as a steady state. This is an ideal situation, an extreme simplification of the hidden Markov model.

8 gene drifting; The pioneer effect, the bottleneck effect, is a kind of snowball effect.

9 Natural Selection: Survival and Reproduction; Directional movement is a change in gene frequency. Dynamic equilibrium is life.

10 heterozygotes have a selection advantage, which is an equilibrium achieved by a multi-level game. Positive and negative choices are essentially a feedback mechanism. Hybridization is a multi-level interaction.

11 Adaptation is the equilibrium reached by the interaction between the individual and the environment at multiple levels, that is, the degree of complexity. We use various binary tree therapy algorithms to discover various possible combinations, and we need to do a screening of specific indicators to determine which combinations have greater significance, which can be expressed in terms of fitness from the point of view of the theory of natural selection, but this also needs to be confirmed experimentally, which forms a circular argument. We can start by assuming that different combinations correspond to different signaling pathways, corresponding to different functions (probability distributions), and the prediction of specific combinations is a Bayesian operation of these basic probabilities. The economic thinking that the benefits of a single gene outweigh the losses can be understood in terms of the concept of equilibrium (gene frequency)

12 Evolution at the molecular level is a lower eigenof of classical morphological characteristic changes: neutral evolution, just as the infinitesimal quantities of calculus are neutral. From the similarity between the combination sequences formed by the underlying units, it is possible to infer the possible evolutionary relationship, i.e., homology (inferred by probability, the probability that a theoretically completely random combination has similarity is 1/20^n, although it cannot be completely random, the probability is low enough, so that the similarity can be inferred from the same ancestor with a greater probability).

13 Multi-level evolution: DNA-RNA-protein, which has a certain similarity with the central law, is also a tool for us to compare. Nucleic acid evolution is similar to protein evolution, and its rate is also a function of time, distance, and so on. We need to consider not only the frequencies of individual sites such as nucleotides and amino acids, but also the frequencies of specific combinations such as codons, introns, and so on, and these combinations, i.e., sequences, have greater significance.

14 The hidden Markov model to understand the evolutionary process: the basic assumptions are that different loci are in continuous mutation with the same velocity (transition probability matrix), the alignment of different sequences (BLAST), and the degree of difference pd (= number of differences/sequence length) is a function of time versus variation (as a fixed point that reveals the relationship between sequences at a higher dimensional level). Since mutations may change back to their original appearance after several mutations, we need to further assume the distribution of variations at different loci (the average number of substitutions at each locus is Kaa=-ln(1-pd), and the smaller the average number of substitutions, the higher the homology, such as the Poisson distribution (0, 1, 2...... probability). And some sites can have a certain degree of substitutability. (Replacement rate kaa=Kaa/2T, the annual replacement rate is very low, and there is only a significant change on large time scales) We will find that this evolution is inevitable, which can be proved by the statistical evolution rate is constant, of course, the specific form of evolution can be diverse, which is why our species are so diverse (molecular evolution is the bottom layer of morphological evolution, and it is the equilibrium formed by multi-level competitive games, such as the genome evolution rate of elephant sharks is the slowest in vertebrates, The study of the possible causes is to look for these influencing factors, such as special ecological environment).

15 molecular clocks (fine enough to the infinitesimal molecular level to mimic calculus): A particular macromolecule has a constant rate of evolution across all evolutionary lineages. The unit of molecular evolution MEU, which evolves at 10^-9 per site per year. Of course, we also need to note that the evolution speed of specific parts of the specific sequence species is also different, and it has a certain distribution (the importance has a distribution of one point, and the speed of change also has a certain distribution, such as the unconservative unimportant evolution speed is fast, and the conservative important evolution speed is slow (not immutable, but the risk is greater, so the probability of occurrence is low)), that is, some are fast and some are slow, but according to the continuous assumption and the median value theorem, there must be a value (velocity = The average number of substitutions per locus) can describe the whole. The evolution rate of the same molecule in different species can be different, which can be demonstrated by certain experimental designs, such as the rate of repair, life cycle changes, metabolic rate, etc., which have a certain correlation and can be quantified.

16 In the construction of specific models, the transformations between different bases can be expressed by certain parameters (the substitution of real bases is complex, and the sequence as a result is like the characteristic value of the Markov matrix, but the specific change process is not clear), and these parameters actually represent certain biological mechanisms. The parameters of the transition between AGCTs can be expressed in terms of Markov matrices, and the final equilibrium is a relatively stable constant, such as the average number of base substitutions at the nucleotide site. JC model (does not distinguish between purine pyrimidines and purine conversions) - K2 model (purine pyrimidines conversions have certain parameters). Then there is the combination of nucleotides, codons are secondary structures, we need to consider the degeneracy between codons, some codons can replace their bases without changing the encoded amino acids.

17 Neutral Evolution Theory: Under neutral selection, the probability of substitution occurring on the synonymous substitution site KS and the non-synonymous substitution site KA (the amino acid that changes the code) is the same (the specific situation may fluctuate a little), and the size of KA/KS determines the frequency of amino acid change, which leads to the formation of a certain selection: KA/KS1, which causes more substitutions of amino acid changes, is positive selection (fixation of amino acid changes, i.e., continuation);

18 Genome sequencing data, in different scales of sequence alignment, which undoubtedly requires a lot of computational resources, such as having the algorithm of assembling sequences also needs to be considered. The study of big data at the genome level is the idea of calculus, and the superposition of infinitesimal quantities at the bottom can approximate the structure of higher dimensions (Newton-Leibniz formula, fundamental theorem of calculus). We use a limited number of genes (more than 30,000 genes in humans) to form complex organisms, which rely on the combination of these genes to form a high-dimensional structure, including mechanisms such as variable splicing, which allows the body to express endless possibilities, corresponding to various biological mechanisms.

19SNPs (single nucleotide polymorphisms), indels (insertions/deletions, dynamic programming strategies for sequence matching), haplotypes, duplications. These strategies are the complex mechanisms by which organisms derive adaptation to complex functions. These combinations are actually a kind of hybridization (gene duplications such as polyploidy, gene rearrangements, etc.), i.e., linear combinations.

20 After aligning the key sequences, i.e., genes, possible relationships between other sequences, i.e., non-coding regions, are discovered. This inevitable tendency, compared to the non-existent of creatures, junk. It is a regulatory mechanism other than genes (hyper-conserved).

21 Understanding disease at the molecular level, the most obvious is the functional variation brought about by defects in various genetic structures, which ultimately leads to disharmony (immobility point) at the organism level; Then there are defects at the functional level, that is, defects in the mechanism formed by the combination of various genes and proteins, such as the up-downregulation of the expression of specific signaling pathways. It should form a certain stable system.

22 The formation of species is a steady state, a temporary equilibrium reached by multi-level competitive games, and the result of the formation of molecular level variation, genetic drift, natural selection, and adaptation to this cyclical process. It is an artificially defined concept, an abstract level of the holistic grasp of this complex process, an abstract understanding of organisms with similar characteristics. The formation of species is the result of isolation. Like the branches of a river, species diverge. The different molecules in this dendrogram evolve at different rates. And there is actually a certain competitive game between these branches, such as the collapse of the wave function/the interference of light, and the last species is the path to survival. Thus there is also the possibility of extinction, speciation and extinction are originally a pair of twins (recursive structure), and extinction can be seen as a kind of pruning (refer to the binary tree algorithm) so that the species formed is competitive (local optimal solution).

23 The doctrine of punctuated equilibrium (in the further development of the gradualism): the evolution of species is the result of alternating long-term steady states and brief periods of drastic change; The variation of finite genes can produce large enough changes, and the search for these genes is a kind of optimal path solution (fixed point), of course, the calculation method in nature is large-scale reproduction and selection, and what can survive is the local optimal solution. Therefore, genetic diversity is a prerequisite that can be solved, so that in the end, it can not converge to the overall optimal result.

24 The low fertility rate of wild animals in farming is due to multiple levels of reasons and is a feedback structure. Therefore, the adoption of various protective measures may have the opposite effect, because the specific existence is the dynamic equilibrium formed by the multi-factor competitive game in the background. We need to fully consider all kinds of complex relationships, and the rules of nature are the local optimal paths formed before (e.g., small-scale arson can reduce large-scale fires, protective damage), which can be followed to reduce large-scale trial and error, that is, reduce computing resources. Referring to the Lenz's law of physics, there are always secondary changes that resist the primary change, and we need to target from multiple levels to really achieve the results we need. Systems engineering requires us to establish a better model, which regards the whole as a living organism, and can form a system through multi-level regulation, which is essentially a kind of dynamic equilibrium.

25 Phylogeney is a way to understand the structure of a system. Constructing a phylogenetic tree can help understand these complex relationships. It is discovered through the alignment of sequences, as well as various similarities such as ecology, behavior, location, and so on. These trees are functions formed from the data (the objective function is the real tree, we just approximate by reducing the error), and the specific parameters can be changed, that is, the specific order may have certain differences. Various methods are used to construct phylogenetic trees: distance method (sequence alignment), parsimony method (idea of greedy algorithm), maximum likelihood method, Bayesian method. There are certain packages for these methods that we can try to write ourselves.

26 What life is, understood in terms of the origin of life. Miller devised experiments to confirm the possibility of the existence of the original soup. It can also be understood from the perspective of artificial life, webuildthenweknow. We cannot play the role of cell generation from the primitive soup, but use the combination of genes to construct the living substances necessary for life. Such as transplanting the genome of a bacterium to another bacterium (Science 317:632-638). We have to consider what the boundaries between living and non-living things are. Life is about infinite possibilities.

27 Evolution of life: Prokaryotic cells—eukaryotic cells, which are the evolution of fractal structures like in nature. Perhaps the Cambrian Big Bang was a post-singularity manifestation.

28 Life is equal.