The first one, then the rest are probabilities.

Any genetic or genomic change occurs in a single chromosome in a single cell of a single individual. The change is personal and private. No exception.

When the cell divides, the change is inherited by the daughter cells and their progeny. This is the only way to increase the number of cells having the same change.

Then, the change in a single chromosome in a single cell of a single organism becomes a variant population within the original population. Then, perhaps, the majority eventually.

Before becoming a population, it always starts with one. Is this first one already a new species? How does it separate from all the other originals? Does the first genetic/genomic change need to cause an immediate phenotypic change? How much should be different? These points are tremendously important but have been ignored in current evolutionary theories.

It has been naively thought that heritable phenotypic variation pre-exists in a population before selection. This is generally explained as random consistent errors in DNA sequence replication that constantly produce new heritable phenotypic variation. Then, any subtle better is constantly selected.

Theoretically plausible. Seems to work in virus evolution, where there is one copy of a minimal set of genes and a simple gene network. Any changes in the DNA/RNA sequence affect its phenotype and, for a simple fitness goal - replication.

Prokaryotes, mostly bacteria, also carry only one copy of their genes, called haploid. However, they have metabolism and its regulatory genes. They have a more complex gene and molecular network within a cell. A complex network is plastic, robust, and adaptable to intrinsic and extrinsic changes through compensation. Imagine unlimited route options for navigating a big city. Many detours. Closing one route is not always a big deal. Multiple closures on one section would be highly problematic, while spreading over to the city would be tolerated.

Eukaryotes, those we see as animals and plants, carry two copies of their genes, called diploids. Some genes require both copies, but most are sufficient with only one. The deficiency in one copy is tolerated. Compared to haploids, more robust because of one copy working as a backup. The number of genes is higher than in prokaryotes and the complexity of the gene and molecular network within a cell is much higher. This means more plastic, more robust, and more adaptable. Many more detours.

Multicellularity and social behaviour development further increase complexity.  This means furthermore plastic, furthermore robust, and furthermore adaptable than unicellular organisms. Many furthermore detours. 

The impact of a change in DNA sequence on phenotypic changes is getting smaller and smaller. Please do not misunderstand here. I am not saying the changes in DNA sequence cannot be reflected in the phenotype. In a simple system, any change can be reflected in the phenotype, whereas in a complex system, some changes can be reflected, but most will not. Absorbed and compensated.

This also creates an interesting but essential problem. The heritability of the genetic phenotype from parents to offspring cannot be guaranteed. What occurs easily in a simple system does not occur at all, or requires very specific conditions, in a complex system.  

Back to the original point. Any genetic or genomic change occurs in a single chromosome in a single cell of a single individual. How does this link to phenotypes? How does the first one expand as a variant in a population, then become the majority (or common)?

In diploid organisms, this relationship between genotype and phenotype is categorized into three groups: dominant, meaning that one allele change is sufficient to exhibit phenotypic changes; recessive, meaning that both alleles must be changed to exhibit phenotypic changes; or neutral, meaning it does not affect phenotypic changes. This is highly simplistic, but it gives a basic idea of genetics in diploid cells.

A single gene is linked to a single phenotype. This is called monogenic traits. The gene works independent from others. Many cosmetic and physiological traits are monogenic traits. Their genes function primarily at the final stage of development or only in adulthood.

On the other hand, genes that act early in development interact with many other genes in a complex network. The gene-phenotype relationship is not linear and simple one-to-one. Through interactions with other genes, compensation and exaggeration of phenotypes could happen. 

This robust stability creates commonality within a population.  A species is a group of individuals sharing a stable, consistent range of anatomical and morphological properties. A species is primarily defined by the anatomical and morphological commonality that is usually established in development. Two closely related species are not drastically different but present stable, consistent, subtle multiple differences in anatomy and morphology. They are regulated by multiple genes and their interactions. The consequence of two distinct complex networks.

Building a new complex network from the original complex network is not easy at all. Because the original complex network is highly plastic and robust. It is unlikely that the accumulation of small changes suffices.

Can we change multigenic traits in one event? Two ways of thinking.

Gradual and tipping over. Imagine a Japanese Shisi-odosi. If you don’t know it, Google it. A nicely designed, seesaw-balanced bamboo cylinder under a tiny water fall. Water gradually accumulates on one side of the cylinder. Then, eventually, it flips. All the water is spilled out, and the cylinder is returned to the original position with a knocking noise.

The other one is shuffling, duplicating or trimming. Imagine you go for a haircut. Growing hair is a very slow, gradual process, but no one tries to do a slow, gradual haircut. There can be differences in magnitude, like partially or entirely, in shuffling, duplicating and trimming. But each step is not gradual and reversible, like a ratchet gear.  

I consider that each organism is a story. A DNA sequence is equivalent to a letter sequence in language. Genes are words. Grammar is a gene regulatory network. Each sentence is equivalent to a protein functional cascade. Paragraphs and chapters are tissues and organs. As a whole, a story emerges like an organism.

When replicating a story, typos and small errors occur. Maybe they affect a small section of the story flow, but not the entire story.  But shuffling, duplicating, or trimming could completely change the storyline, leaving no typos or small errors.

Importantly, a story of a living organism is not oral literature. It is written on the material – DNA polymers. It can be shuffled, duplicated and trimmed as materials. Imagine a book. Errors in a book are not limited to typos. Shuffling, duplicating or missing pages. It can create a completely different story or the same story with a different sequence of events. A love story can become an adventure. Two similar adventure stories, but the main characters and bystanders could be flipped. Dynamic editing can completely change the original plots.

Everyone can agree that if this occurs at the microsequence level, it will destroy gene function because the DNA sequence encodes an amino-acid sequence of a protein. The change in DNA sequence causes the change of amino-acid sequence of a protein. Changes in amino acid sequence alter protein shape and properties, which are the essence of its function.  

How about the macrosequence level? Does the macro sequence level in a DNA polymer play any role in the story of a living organism? I believe so. Not only I, but Richard Goldshimidt was the first one to think like this. In his book “The material basis of evolution” in 1940, he considered the importance of the structural patterns within a chromosome. This was the time when no one knew the identity of genes and the double helical structure of DNA.  The mainstream idea of genes was represented as the beads on a string theory. Each gene is atomic, independent from the others surrounding it. On the other hand, Goldschmidt proposed that something organic is encoded in the pattern within a chromosome.

Shuffling blocks within a chromosome. Chromosome rearrangement. He considered that the macroscopic order within a chromosome must carry heritable information for individual species.

I believe that his insight was correct. Astonishingly correct.

In modern words, this could be explained as long-range enhancers, 3D chromosomal structures and DNA synteny. Although no one currently supports this idea due to a lack of evidence, I believe it will soon replace the current theory.

I do not have direct proof at this point. But I believe that the Wnt9b-Wnt3-Nsf locus is the putative locus explained the genomic events for the emergence of the first jawed vertebrates (placoderms) and the later emergence of ray-finned fish.

An insertion of the Nsf1 gene (200Kb DNA sequence in mice) next to the Wnt3 locus must be contributed for the emergence of the female reproductive tract (FRT), hind-limbs and jaws. A translocation of the Wnt3-Nsf cassette (300Kb DNA sequence in mice) removed the FRT development, compromised limb development and modified jaw structure.

As Goldschmidt predicted, these chromosomal events can modify the expression of important developmental secretory molecules (i.e. two Wnt ligands) in early development.

The interesting point of chromosomal rearrangement is that one event can impact an organism’s phenotype and reproductive activities. In my knowledge, no single gene alteration can achieve this simultaneously.

As I repeatedly mentioned, any chromosomal event occurs in a single chromosome in a single cell of a single individual. If the change is dominant, its phenotype is exhibited in this individual, while if the change is recessive, no phenotype is exhibited in this individual.

However, reproduction is a different story. A chromosomal event (i.e. inversion, deletion or translocation) can cause reproductive problems spanning from sterility, subfertility, to no issue at all. In the first individual, one chromosome is the original, and the other is modified, say, with an inversion. This heterozygous condition of two homologous chromosomes can cause problems with successful meiosis. During meiosis, two homologous chromosomes need to align to exchange genetic material via recombination. If the two chromosomes are not aligned, this process cannot be completed and results in meiosis failure. This is not an all-or-nothing event, like a success rate.  If the rate is low, the individual becomes sterile, and if the rate is high, it does not differ from others. In the middle, subfertility. The total number of sperm or oocytes may be lower than usual, but those formed should function normally.  

The first individual has no choice but to mate with the normal original. Their offspring will be 50% heterozygous, carrying the inverted chromosome. In this generation (F1), there is no chance of exhibiting recessive phenotypes, but the problem in meiosis will persist. Then, if those heterozygous intercross through sibling mating, 25% of the offspring will be homozygous in this F2 generation.

Now, the inverted chromosome becomes homozygous. Recessive phenotypic traits could be exhibited. Interestingly, in the homozygous individuals, there is no reproductive problem now. The two inverted chromosomes have no issue in homologous chromosome alignment. Their reproductive ability should be fully back to normal.  

If two homozygous individuals mate, there is no problem in reproduction to generate the F3 generation. Both parents and offspring should exhibit the recessive phenotype.

If the recessive phenotype from the inversion impacts the phenotypes, and these new phenotypes open a new probability, these individuals continue as a new species.

The new probability is not competing but opening where no probability existed for unknown reasons. Only after a new species emerges is the previous reason for unihability realized retrospectively. In hindsight, the process makes perfect sense.

Interestingly, not only does the recessive phenotype from the inversion chromosome, but also the founder effect, accidentally fix many other minor phenotypic traits. I believe the founder effect must create stable, consistent, subtle phenotypic differences between two closely related species.

Evolution is not competition. A series of step-by-step speciation, each step opens a probability where there was none. In this line, it is important to realize that a species’ commonality does not change from its emergence to extinction. Making a new commonality suitable for occupying an empty open niche, which is previously uninhabitable, is evolution. Therefore, biodiversity has been increased, and almost the entire surface of the Earth is occupied by living organisms.

The first life is an accident of abundance and ubiquitous in the local environment. The beginning of life was realized only after two or more sister cells formed. The first cells were not living organisms. Only after successful reproduction, i.e. two or more sister cells, was the first one recognized as living retrospectively. From nothing to the first cells. Then, the reproduced sister cells allowed to realize the reproduction of the first cell – the beginning of life.

The reproduction was a probabilistic event. But it was high enough to continue as a whole progeny. Prospectively, no one can predict which one continues; however, retrospectively, always a single path down to the first one.

The survival of individuals is the probability in their local environment. The population size is set as an equilibrium between intrinsic properties and adjacent extrinsic conditions.  

This probability is fully dependent on the local abundant and ubiquitous resources. The local abundance supports the probability of species’ continuity, but simultaneously constrains where the species can continue.  

When a change in intrinsic properties opens a new probability of reproduction in previously zero-probability at the physically accessible areas, a new species emerges.

Probability cannot be competed. Probability is shared and layered. Upper layers’ probabilities impact lower layers’ ones but not the other way around. Because probability is something to be shared, it is impossible to completely eliminate opponents. When the probabilities that one species relies on disappear or are not high enough for a sufficient number of survivors to continue, the species will become extinct.

Extinction is not the consequence of losing in all competitions. Extinction happens when no opportunity is available - deprivation of the probability.

The natural world consists of sharing probabilities and opening a probability. Human cognition and technologies enable the modulation of probabilities and open new ones without creating a new species. Simultaneously, humans have deprived the probabilities of many other species because we open new ones for ourselves at the upstream of others. This leads them to extinction.