Free Time Research

Keratin genes provides us with another illustrious example of how protein variants evolve in parallel with the evolution of organisms. Keratin consists of a family of structural fibrous proteins called intermediate filaments. The master gene of keratin is present as early as in sea squirts before Cambrian explosion. Today numerous variants of keratin exist in a vast variety of species, including vertebrates and invertebrates. They form the hair, outer layer of skin, horns, nails, claws, scales, shells, feathers, beaks and hooves for sea squirts, fishes, reptiles, birds, and mammals. It’s the sweeping divergence of keratin master gene in the past 600 million years that has made variety forms of such tough structures possible. And it’s these variety forms of tough structures that confer animals bearing one of these structures distinct capacity to inhabit a suitable environment. A particular keratin variant can function in many species, and a particular species can have many keratin variants to fulfill different functions. For example, The human genome encodes 54 functional keratin genes, located in two clusters on chromosomes 12 and 17. It’s clear that the distinct amino acid sequence of each keratin variant has been preserved over the evolution for advantage in its unique three dimensional structure that is just suitable to build beaks, or feathers, or hair, or nails, etc.
 

The first generation of protein variant deviates from its master protein through random changes in its amino acid sequences. The second generation of protein variant deviates from the first generation of the protein variant through random changes in its amino acid sequences. After round and round of deviation and evolution cycle and evolution cycle, it forms a large family of variants. However this is a family of variants from evolution point of view, they are unlikely a family of variants from structure and biochemical function point of view. In other words, a master gene could have diverged into a giant group of protein variants over evolution, and many of them are completely different from others in amino acid sequences, biochemical functions and three dimensional structures. They have lost qualifications to be variants of other members per se, but are all-new protein molecules on their own. Evolution placed no constraints on duplicate genes to diverge as long as a variant is not lethal to the organism. Generation of an all-new protein from a duplicate gene is obviously a far better choice than from a piece of random DNA sequence, because the duplicate is blessed with a full gene structure. A gene can be transformed into a new functional gene through random point mutations, exon and regulatory sequences shuffling, alternative splicing, and etc. on various parts of the gene.

The large gene counts of multicellular species in the pre-Cambrian period seemed to be an indicator of accumulation of duplicated genes over 1 billion years, and their roles were manifested in the Cambrian explosion and all later evolutionary events.

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6. New Species Arise in Explosive Mode – Evolution Cycle

It seems bewildering why all over a sudden evolution accelerated, bringing millions of complex and advanced new species into existence in a short period of time. In Stage 3, a burst of new species in general accompanied certain dramatic climate and geological changes. For example the Cambrian world differed greatly from the preceding Proterozoic Eon in terms of climate and geography. During the transition of the two periods, the earth experienced a gradual global warming, rising oxygen level, and split of a single continent into two. Climate and geological changes could make mutations occur more frequently in all species. When mutations struck DNA polymerases, DNA polymerases replicated DNA at lower fidelity, causing organisms to suffer from accelerated genetic changes. Direct consequences of this are two folds, mass extinction of old species and proliferation of new species.

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Prior to Cambrian explosion, the majority of living organisms were small, unicellular, and simple, classified under kingdom protists, including slime molds and fungi, while a little more complex, multicellular organisms like sponges, jellyfish, sea anemones, corals, etc just gradually emerged in the later stage of slow evolution. Living organisms exploded into millions of forms and complexities during Cambrian period. Many organisms we see today appeared in this period, for example, insects, flies, spiders, centipedes, shrimps, ticks, mites, scorpions, snails, shells, starfish, brittle stars, sea urchins, sand dollars and sea cucumbers. First plants and fishes appeared at the later stage of Cambrian period. From evolution point of view all these species remain very low on the evolutionary ladder despite of stunning varieties in complexities and forms.

In the following 540 million years, evolution greatly sped up the emergence of new species of higher complexities. In a nutshell, evolution of species is the evolution of genomes. The genomes became more advanced after each evolutionary event, laying down the foundation for more complex and advanced species to appear.

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As described earlier, when organisms evolve to higher levels, they rely more on protein variants to build unique morphology, cellular structures and biochemical processes. Protein sequence comparisons tell a lot about those proteins that play similar biological roles in different species. A large number of those proteins can be classified into groups based on the similarities of overall amino acid sequences or sharing of certain short amino acid sequences called motifs. Proteins that shared similarities of overall amino acid sequences are essentially variants or isoforms of each other. By taking advantage of protein variants and motifs, the creation of proteins with desired functions and properties became easier, and at the same time it alleviated the challenge to assimilate new biological components into existing cellular structures and biochemical processes. Otherwise it would incur a formidable array of problems for creation and integration of all new proteins into the existing system even when organisms were low and relatively simple as it had been vividly shown and told in the slow evolution stage.

Evolution is a process of constant changing, and constant changes bring about all sorts of consequences to the organisms. It’s highly unlikely that all modern day organisms, archaea, bacteria, animals and plants, are in the path of evolution. The planet earth is full of living organisms as simple as single celled life and as complex as mammals. If all organisms were in a constant state of evolution over the past billions or millions of years, we wouldn’t be able to see organisms as low as archaea, bacteria, algae, fungi, even jelly fish, sea urchins, etc. This indicates that not all low organisms can be ancestors of higher organisms. Most species stay where they have been since they appeared long time ago.

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The concept “ancestor” must be right because it agrees with the evolution of living things. Then what organisms can be ancestors from which higher forms of life arise? Formation of new species isn’t a simple event, but involves numerous changes in the genotype that generates a phenotype that is sufficiently different from the phenotype of the old species. This level of genetic changes won’t be possible in a normal organism, implying that ancestor organism was special on its own. The genome of ancestor organisms was likely to be quite elastic and blessed with a genetic machinery that could perform large-scale genetic changes – changes that will generate enough new genes or gene variants for a new phenotype that defines an organism as a new species.

What exact events could trigger large scale genome changes is a forever mystery just as how life exactly started, unless humans could be fortunate enough to experience a new round of mass extinction and mass formation and we were not part of the mass extinction. However, it’s worth to think about it and envision something fictitious to get some idea.

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In usual time, genomes of all organisms, including ancestor organisms, were in a disarmed state, in which the genome is consistent and stable except low random point mutations and normal DNA recombinational events during meiosis. When sudden geological and climate changes broke out, ancestor organisms in a population suffered from more mutations. When mutations lessened the replication fidelity of DNA polymerases, genome wide accumulation of point mutations accelerated. These genetic changes acted as a perturbation that drove the genome from its disarmed state to an inconsistent and unstable state, an armed state. In the armed state the genetic machinery of an individual ancestor was activated to perform genetic changes that would reshape the genome to start the evolutionary event, a phase called genotype reshape. Genotype reshape initially reshaped the genome, but as it brought further changes to the genome, the genome gradually re-established a consistent and stable state, a new disarmed state. This was a process called genotype healing. After genomes of all individuals descending from the common ancestors went from disarmed state to armed state and then back to a new disarmed state, it completed one evolution cycle (Figure 3). All individuals that appeared in the cycle, including those dead at the embryonic stage, were intermediates of the evolution. Processes reshape and healing are quite blurry and overlapping, but are two different concepts useful to reveal what is happening in an evolution cycle.

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Figure 3. Evolution cycle from ancestor organisms in disarmed states to new species in new disarmed states, including two processes reshape and healing and numerous intermediates in armed states. Reshape and healing are largely overlapping, as some mutations bring changes to make genes defect-like and others to turn them back into functional variants or new genes.

Genome evolution cycle is unique because it could take up to 10 million and even 100 million years or generations to complete just one single cycle, and its cycle path is composed of a single armed state and two processes, reshape and healing. From genetic mutation point of view, all changes that occurred in the path are random and irregular. Randomness and irregularity are the key to the fascinating biodiversity that arises after each evolution cycle. Genetic changes that occurred in a cycle are deemed as large-scale, but the changes to one generation of any intermediate must be on a granular level so that some intermediates in the population would survive every change. Not all evolution cycles would lead to new species if no intermediates survived.

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Assume there was a population of a single ancestor species before sudden geological and climate changes. When physical upheaval came, all genomes were hit with random mutations and entered an armed state. As a result one armed state was different from all other armed states among the population in terns of DNA sequences thanks to the randomness of mutations. The judge of a change to be good, bad, or not-good-not-bad is if the intermediates could survive the change. In an evolution cycle, all lethal changes were eliminated from the population after causing carriers to die, leaving no impact in the evolution cycle. Only changes that could be passed down to the next viable generation would have impact and cause phenotypes of the next generations to vary.

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After entering the cycle the homogeneous population of the ancestor quickly became heterogeneous in terms of genotypes. As the cycle continued, more random and irregular genetic changes made the genotypes of the population more heterogeneous. In other words, the genotypes among individual intermediates became different after a few generations and the differences widened as more generations passed. Eventually at the end of healing process and arrival at a new disarmed state, survived individuals carried genotypes that were so different from one another, and they were no longer the same species, but different new species. The genomes of all intermediates were in armed state, and their fate in the cycle was unpredictable in the random world. It’s all up to their luck.

Mutations generated in the early stage of reshape would perturb the normal biochemical machine and cellular structures to a greater extent, giving the cycle a bumpy start. The perturbation could lead to the death of most of early intermediates, but it would be necessary for an evolution cycle to produce new species. As process healing was slowly overtaking process reshape, any new components, including protein variants or new proteins if any, gradually reached an equilibrium with the existing system after undergoing numerous changes throughout the cycle. In addition the morphology of each intermediate underwent corresponding changes as the genotype changed. The happy ending of an evolution cycle was the emergence of new species in new disarmed states. In this state all biochemical and cellular functions were balanced again after they had been agitated by genome wide changes and returned back to work in harmony, a result of enduring long time instability and biochemical conflicts. The difficulty to achieve such a balanced or disarmed state would be unthinkable if numerous protein variants were not part of the cycle, especially in species as advanced as fishes, amphibians, etc. It is expected that overwhelming majority of intermediates couldn’t reach the final disarmed state, but disappeared quietly because of failure to survive seemingly endless mutations. They are the dead ends in the cycle.

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The random nature of genetic changes could result in a number of first generation intermediates, depending on the size of ancestor population. From the moment of birth, an intermediate would move along its own path in the cycle and produce its own next generation intermediates in a manner independent of other intermediates. It was unlikely to predict how many more generations were needed for a random intermediate to reach the final disarmed state if it was a lucky one. New species would resemble each other more strongly if they descended from the same intermediate fewer generations apart and differ with each other more strongly if they were more generations apart. Figure 4 illustrates an evolution cycle in its entirety starting from an ancestor population. Individual ancestors (orange solid circles) sit in the center and were surrounded by light pink sold circles that represent numerous intermediates, whose distance to the center represents the number of generations down from the ancestor. Intermediates that are dead ends in the cycle are represented by outermost solid black circles. Some lucky intermediates that end up in disarmed states – the new species arising from this evolution cycle – are indicated by outermost solid red circles. When a line with arrow connects the center and one of the outermost circles through a series of intermediates in between, we could see the complete evolution trails that start from an individual ancestor and passes through every intermediate that leads to the next intermediate before reaching the outermost circle. The picture clearly shows that new species arise in an explosive mode in an evolution cycle totally due to the random nature of genetic changes. Therefore the size of new species descending from one common ancestor is determined by the number of intermediates that survive to the disarmed states.

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Figure 4. A simplified diagram to illustrate how new species arise in explosive mode in one evolution cycle. Distribution of new species is random relative to the ancestor organism. All new species can be classified into a single class.

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We can use human evolution to help illustrate an evolution cycle at work, rough but a little more intuitive. It is more appropriate to say that all mammals arose not from a single ancestor, but from distinct ancestors that shared a lot of similarities. About 60 million years ago there was one ancestor X0. X0 could be an ancestor organism or an intermediate from another ancestor organism. Regardless of its origin, it diverged into a number of intermediates after X1 generations. One intermediate led to a variety of monkeys (disarmed states) after X2 generations with many intermediates becoming dead ends in the cycle. Another intermediate diverged into more intermediates of its own after X3 generations, among which one intermediate developed into early ape species (a disarmed state) after X4 generations, and another intermediate moved on and diverged into more intermediates of its own. One intermediate became gorilla (a disarmed state) after X5 generations, and another intermediate moved on and produced more of its own intermediates. One intermediate among them developed into different forms of chimpanzees (disarmed states) after X6 generations, and another intermediate moved on and led to more intermediates. One of these intermediates finally reached the earliest two-footed animal bipeda after X7 generations, establishing genus homo. This earliest two-footed animal bipeda wasn’t a dead end, but a lucky intermediate on evolution that generated an unknown number of its own intermediates, one of which led to humans, the only species (a disarmed state) emerged from this lucky intermediate after X8 generations. Which species first reached its disarmed state in the cycle can’t be speculated but must be established by research, especially through DNA sequence comparison. Some intermediates left fossils behind that allowed researchers to trace human evolution in the past 3 million years. However scarcity of fossils have limited progress in this field.

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In biology, there is a classification system that classifies living organisms into eight levels based on shared characteristics. The last four levels are order, family, genus, and species. Animal gorilla can be classified to the last four levels as primate order, hominidae family, gorilla genus, and gorilla species. In similar way, chimpanzee as primate order, hominidae family, pan genus, and chimpanzee species, and human as primate order, hominidae family, homo habilis genus, and homo sapiens species. It would be obvious now that gorilla, chimpanzee and human share the same ancestor and a series of common intermediates until reaching a particular intermediate, from which gorilla left the trail to human and established its own genus gorilla. Chimpanzee and human continued to share some common intermediates before chimpanzees diverged from the trail to human and established its own genus pan. However, the order of appearance can’t be determined purely based on which species is more advanced physiologically and morphologically. In other words, the appearance of chimpanzees was not necessarily earlier than humans. Nevertheless, if this evolution cycle ended at the time of modern human emergence, then it is ended about 30,000 years ago.

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Since the beginning of Cambrian period, life evolves through evolution cycles, and what happened in Cambrian explosion has also happened in human evolution albeit more complexity and higher richness in genetic materials.

New species are most likely to stay in a disarmed state indefinitely as long as their natural habitats are not too harsh to endanger them. Evolution has been a continuous process. While numerous new species emerged from intermediates in evolution cycles, certain intermediates would transit into new generation of ancestors – daughter ancestor – to keep evolution going. When their DNA polymerases and related enzymes lost their high replication fidelity upon sudden geological and climate changes, they would become a driving force to start new evolution cycles, making evolution of life an inevitable and sure thing to happen. It’s an interesting and intriguing mystery if any potential ancestors are still crawling somewhere on the earth, waiting for a geologic event to rouse their evolutionary spirit.

Randomness has been changing its meanings since life-like activity appeared in the incubator in the nascent earth, and is tightly connected to the evolution of living organisms. On the macro level, randomness in Stage 1 and Stage 2 leads to heterogeneity of all organisms in the entire living population as each individual organism carries its own unique genome. If each of these individual organisms diverges into a few new species, new species arise in exponential mode. On the micro level, emergence of a new species is the result of establishing a new balanced biological system, in which a series of changes brought up by the expression of new functional genes would be integrated into the existing system. As species become more complex and advanced, macro level randomness no longer refers to the genome uniqueness of individual organisms, but refers to the genome uniqueness of a population of a particular species, while micro level randomness remains the same.

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Randomness is the driving force of evolution throughout the entire evolutionary history. In the dark period of time, only vast randomness embedded in a mess can give rise to something good, which is what exactly had happened in the life incubator 3.5 billion years ago. Time is infinite enough to allow evolution to progress at a snail’s pace.

Fossil records give approximate time species appear on the earth, but no clues could be drawn to show the time an ancestor organism began to evolve. In other words, the end of an evolution cycle is relatively clear, but its beginning isn’t. Genome sequence comparison would be the only resort to determine the closeness of the species on the evolutionary ladder by establishing the degree of the homology of their genome sequences.

From evolution point of view, it doesn’t make sense to consider genes that had small, even no tolerance to genetic changes in the cycle. These genes are too fundamental to life and have little margin for further changes. Mutations would occur to them as usual, but the consequences are either lethal or minuscule in derivation of new functionality. These genes should be excluded in the evolutionary process. What makes sense is to look at genes that have great tolerance to genetic changes. It’s these genes that drive evolution forwards as they are able to accept random mutations and deviate into a variety of isoforms or even totally independent forms. Opsin and Keratin genes are the typical examples. It’s these genes as well that make it possible to change the complex phenotype in a relatively short time.

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Genome sizes and protein coding gene counts shown in Table 1 provided a hint at what happened in the slow evolution stage. Table 2 shows similar information for post-Cambrian species to reveal what evolution is really about in the fast evolution stage.

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Table 2. Genome sizes of various species on different levels of evolution. Data are taken from Ensembl.

Data are largely identical to what is shown in Table 1, but genome sizes increase significantly as species move up the evolutionary ladder. Invertebrates ciona intestinalis and ciona savignyi are low species from Cambrian explosion. Their genomes are relatively small, only 100 to 200 millions base pairs, but contain around 10,00 to 20,000 protein coding genes, about 50% to 100% of the protein coding gene counts of mammals. Tropical clawed frog genome contains about 22,000 protein-coding genes, which are comparable with the numbers from humans while its genome is only about half the size of humans. Exact number are virtually impossible to obtain just by analyzing the entire genome sequences, but it gives us a rough idea that gene counts and genome sizes are not proportional. Protein-coding gene counts from fishes to mammals are largely similar, ranging approximately from 15,000 to 25,000. An important implication of these numbers is that each evolution cycle, for example from fishes to amphibians or reptiles to mammals, seems to need few all-new proteins to become new species. An implication of this is that protein variants seem to play more significant roles than we thought.

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If the total number of genes, on average, was assumed to be 30,000, including non-coding genes and pseudogenes, at the onset of an evolution cycle. The genetic changes, including gene duplication, must happen to these 30,000 genetic loci to be effective for evolution. If one evolution cycle took 10 million years, all genetic changes that finally brought about new species must complete in this 10 million years. DNA recombination is largely independent of point mutations, and the occurrence of one would not interfere with the other. A likely scenario is that DNA recombination during meiosis might occur more frequently in the early phase of the cycle, adding more gene-like loci into the gene pool. Overall DNA recombinational events would be less frequent than point mutations. Throughout the entire cycle, gene pool could reach slowly a final count of up to 40,000. The pro-evolution DNA polymerases would introduce more random point mutations at higher frequencies into the entire genome with certain percentage falling onto the genes in the pool. It’s these random point mutations that slowly but steadily transformed the grand old landscape of biochemical processes and cellular structures into a new species. But it’s more appropriate to look at evolution from mutations that occur to the entire genome.

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In a hypothesized scenario for the purpose of illustration, suppose there was a single individual ancestor organism with a genome size of 1 billion bps and one evolution cycle resulted in one new species. In other words, there was only one evolution trail in the cycle. On average many animals produce offspring one year after birth, meaning one generation per year. If pro-evolution DNA polymerases incorporates 5 random point mutations in one meiosis per 1 billion bps, equal to 5X10-9 per base pair per generation. If the length of one cycle is 10 million years, the final species could have accumulated about 50 million mutations in one cycle. This means that 5% of the bases have undergone mutations after 10 million generations. Assume each gene contained 600 bases to encode 200 amino acids on average and 200 bases for regulatory sequences to control gene expression, the gene had a chance of a single point mutation 4X10-6 per generation. Among 40,000 genes, 1,000 were immutable, and the chance for the remaining 39,000 genes to be hit with one single point mutation was only 15.6%, meaning even not a single gene would be subjected to one point mutation per generation. Over 10 million generations, the chance for each base pair to receive 1 point mutation is only 5%, which translated into one gene for 40 point mutations, and 39,000 genes for 1,560,000 point mutations. If mutation rate increased to 10 and the length of an evolution cycle increased to 20 million years, then average mutations for one gene would be 160 in one cycle. Be noted that the weight of 40 mutations on a protein variant is much heavier than on an all-new protein, indirectly indicating the importance of protein variants in the fast evolution stage.

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The above estimate is very misleading. 40 point mutations per gene per 10 million years seemed too scanty to bring about a new species. However, the average number of offspring per generation per one pair of parent organisms would make huge difference. For easy estimate, if the average number of offspring was assumed to be 10, which was equivalent to 5 parents, and life span was 2 years, then the total number of offspring at 10 millionth years would be an astronomical number, about 55,000,000. With such a large number, a single gene had undergone approximately 55,000,000 point mutations over 10 million years, making any possibilities possible even taking large mortality rates among intermediates into consideration. These mind-boggling numbers result in the enormous heterogeneity of the intermediate population in a cycle and are the basis of emergence of new species in explosive mode.

When we look at evolution from the whole genome, we could see a thread of events that go through the evolution cycle. Random mutations change the discrete bases in genes, and the discrete base changes result in discrete changes in amino acid sequences encoded by these mutated genes, which affect the biochemical properties of the proteins in a discrete manner. It can’t be predicted that how the discrete changes in biochemical properties will change the proteins’ functions in their normal environments. Regardless of the discrete changes from new proteins or existing proteins, the final effects are discrete, reflecting on the survivability of the organisms. If the mutations render protein products incompatible with the existing system, causing disruption of essential biochemical processes or collapse of cellular structures or death of organisms, they are lethal and would be eliminated from the populations immediately. Only neutral and beneficial mutations would be preserved and accumulate throughout the entire cycle to finally decide the forms of new species emerged at the end of a cycle.

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It would be difficult at present to predict which protein factors played critical roles in determining the final fate of an intermediate. But it could be predicted with confidence that some protein factors play deterministic roles in the establishment of the morphology of an organism, for example, setting the general predisposition of organs in the body, deciding body shapes, brain size, development of feather not limb, etc. all of which are visible phenotype. However, coalescing and integrating all new and changed properties into existing system is painfully long and purely of trial and error nature over tens of million years. More often intermediates would perish due to genetic changes that were incompatible with the existing activities before reaching the end of a cycle.

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From evolution point of view, the genomes of ancestor organisms is more likely to be small and compact. A small genome allows recombinational events and point mutations to concentrate more on significant loci rather than on vast non-coding regions, which is more cost-effective and prolific. A small genome offers more margin for size increase due to DNA recombinational events like gene duplication. Gene duplication seemed to take place in every evolution cycle, and protein variants were more likely to be derived from active genes that were just duplicated in the cycle, as it was the most economical approach to obtain desired properties with minimum changes. Any “leftover” duplicated genes from earlier evolution cycles might have lost structures of an active gene, and couldn’t serve as suitable genetic sources for new properties. A direct measurable consequence is the genome size increase without an increase in protein coding gene counts after each evolution cycle.

It can be concluded that division of evolutionary timeline into slow and fast stages is scientific as two fundamentally distinct mechanisms are working behind each stage. A stage that took over 3.5 billion year to complete reflected the daunting difficulties in creation of thousands of all-new genes from random sequences and assimilation of those all-new properties into the existing system to generate a vibrant and robust system with great potential for further development. The net result of the slow stage is to build up protein coding gene counts that approach to the level of higher species, including mammals, while keep a morphology as simple as multicellular life could be. Apparent incompatibility between abundance of protein coding genes and simplicity of a morphology indirectly indicates the crudeness and coarseness of the large number of genes created and accumulated in this stage if they really could code for proteins. Regardless of the utility of those large number of genes for the pre-Cambrian organisms, they are the abundant ready-to-use materials to derive new properties to build more sophisticated forms and more variety features. Clearly slow evolution lays the solid foundations for rapid proliferation of new species, and is the preamble to the fast evolution stage.

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The relative stability of protein coding gene counts across the entire post-Cambrian living kingdom argues well with the conclusion that no more than 20,000 protein coding genes are required to build an organism as sophisticated as humans, and the majority of protein coding genes in higher animals are descended from counterparts in lower species. The main task of the fast evolution is to derive new properties from existing properties and assimilate new properties into the existing system to achieve new species with distinct morphology and physiology, in stark contrast with the main task of slow evolution – creation and integration of new protein coding genes from random or semi-random DNA sequences to increase the gene counts. Comparing with slow evolution which is concentrated on creation, fast evolution emphasizes on reuse and recombine through mutation-based derivation. Because of this, post-Cambrian evolution occurs in cycle. In each cycle, random mutations on protein coding genes generate new properties with altered regulatory control, As the cycle proceeds, more new properties appear and change the organisms in an increasingly greater degree, finally resulting in new species as the cycle ends. New properties that appear in a cycle are laid on top of the properties from the previous cycle, and the new species are generally more sophisticated and more advanced than their ancestors virtually in all aspects of a living organism.

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As species become more complex, the underlying biochemical and cellular machines become more delicate and intertwined, requiring great balance among biochemical processes, cellular structures, and all the way to cells, tissues, and organs. An implication is that a simple system is far facile to admit new components and as a result develop into many distinct new species. In contrast, a larger and more intrinsically interlinked system is less tolerant for adding new things in and taking existing things out, so fewer new species. In addition, the size of offspring produced in one reproduction season is positively correlated to the size of new species from a singe ancestor organism due to the enormous heterogeneity of intermediates in an evolution cycle. For example fish account for more than half of vertebrate species with over 33,000 species described.

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Human evolution is an interesting thing to look at. Modern humans appear just 300,000 to 800,00 years ago, while earliest primates appeared at least 90 million years ago. Monkeys that are closer to humans more than many other primates appeared about 40 million years ago, and the ancestors of the gorillas splits with the common ancestors of humans and chimpanzees about 10 million years. Chimpanzees, the closest relative of humans, split from early humans 8 million years ago. The exact time for these species to appear isn’t important, but it’s important to show clearly that the evolution cycle that leads to humans is well more than 50 million years long. DNA sequence comparisons show that genome sequences differ not as big as expected among these species. Single-nucleotide changes account for about 1% of differences, while gene duplications, deletions, and chromosomal rearrangement account for about 3% of the differences. This 1% differences seem to affect 70% of proteins although the differences in amino acid sequences can be as small as only a couple of amino acids.

Humans differ from chimpanzees, gorillas, and other primates so extensively in every aspect from morphology to physiology to the brain size. It seems unlikely that 1% of genome differences mainly from point mutations are able to account for all the differences between two species. There are no such genes that make humans humans or chimpanzees chimpanzees. Rather, this limited genetic changes have refined and honing every bit of genetic materials to form a system in which each gene expresses in such a precision manner in terms of cell type, timing, degree, coordination with others. Derivation and utilization of protein variants in humans are so fine tuned to meet the exact functions of the cell and tissue types. In all likelihood, since splitting with chimpanzees, the mutations on human genome have greatly optimized majority of the genes to achieve the best protein products, best expression in space and timing, best combinations of components to bring up the most beautiful living organism possible.

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All multicellular organisms start from a fertilized egg, while the egg provides only components to walk the first step in the entire life process. From life standpoint, it’s the genome that directs the organism to complete its life cycle without input of external guidance or instructions. From evolution standpoint, the next generation of species always arises from current generation of species. As a result, evolution always moves species forward. From civil engineering standpoint, the genome is the greatest blueprint ever for making things from simple (in the eye of evolution) to unthinkably complicated. It plans and then executes every facet of a building process from design, layout, materials, overall arrangement, maintenance, and all other aspects of engineering so precisely, flawlessly, and in greatest order, details, logic, and forms. A blueprint drawn from every genome can be put into a living marvel, logically arranged, aesthetically pleasing, and economically efficient. Truly the genome is indeed the finest thing ever in the universe.

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7. Rethink of Natural Selection

Natural selection is the process through which some organisms in a population adapt and change better to suit the environment than other organisms in the same population, and as a result survive better and reproduce more offspring. Differential survival and reproduction of individuals are due to genetic variations that produces some favorable traits to give them some surviving advantage in their natural habitat. Upon passage of those favorable traits onto their offspring over generations, individuals of later generations become a better fit for the environment and more common in the population. Through this process of natural selection, favorable genetic variations, thus favorable traits, are transmitted through generations. After inheritable changes that underlie genetic variations in a population accumulated to a substantial amount over unknowable generations, the individuals that carried these changes became a distinctly different new species.

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On the evolutionary timeline eukaryotic organisms appeared to reproduce sexually at the single celled stage about 2 billion years ago. Since then sexual reproduction seemed parallel with the evolution of eukaryotic organisms. Almost all modern eukaryotic organisms produce offspring through their sexual reproduction system. Sexual reproduction is costly and of low efficiency, but it is ubiquitous for all multicellular organisms, indicating that it has advantage over asexual reproduction. Main advantage seems to increase genetic diversity in the population and mitigate accumulation of harmful genetic mutations.

Adoption of sexual reproduction system confers eukaryotic organisms two sets of genomes, germline genome and somatic genome. Information flow between the two genomes is unidirectional from germline genome to somatic genome. As a result, mutations in germline genome will pass on to the somatic genome of next generation, while there exists no mechanism for the organism to transmit somatic mutations good or bad to the germline genome, making somatic mutations short lived to the life span of the mutation carrier. When we talk about mutations, it always refers to heritable germline mutations unless indicated otherwise.

Any mutations can exert one of the three consequences to the organism regardless of being germline mutations or somatic mutations – deleterious, neutral, or beneficial. The current understanding is that it’s natural selection that determines if a mutation is deleterious, neutral, or beneficial. Beneficial mutations produce advantageous traits, which, under natural selection, allow the mutation carrier to survive better or reproduce more offspring, and eventually become more common in the population. Only beneficial and neutral mutations will be passed down from generation to generation.

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Natural selection is a fundamental element of the evolution theory. It illustrates how extraordinary biodiversity on earth has been driven and shaped by natural selection in the entire timeline of evolution in a simple and elegant way. So far there are many examples to demonstrate natural selection at work, and the origin of giraffes’ long necks is the classic one. Giraffe’s ancestor inhabited in dry savannahs of Africa with open plains and woodlands. There trees were tall and hard to reach for animals of normal necks like deer or antelope. Some day certain genetic mutations occurred in the ancestor’s genome, which made ancestor’s necks grow longer. With a longer-neck, these individuals gained advantage to reach leaves on the high position, and as a result, were able to eat more and produce more offspring. As the genetic mutations passed down generation after generation over time, individuals’ necks continued to grow longer until the neck reached the length as of today. Because the long-necks was a favorable trait which made individuals adapted to the dry savannahs better, these individuals finally became the most common in the population, and they were called giraffe. Giraffe is so different from its ancestors that it becomes a new species. It could have taken probably millions of years for giraffe’s ancestor to slowly develop into giraffes as they are today. This explanation seems plausible and uncomplicated even to general public.

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Nevertheless, the development of life through evolution over billions of years can’t be as simple and straightforward as illustrated by natural selection at all. You will encounter unsurmountable blocks if you want to use natural selection to explain evolution a little deeper and in more details. To physically support a longer neck, giraffes will have to pump more blood to the upper body and change its body shape in order to run fast and keep body balanced. Therefore, giraffes must develop stronger skeletal, cardiovascular, and nervous systems and more. To meet these broad requirements, many changes must be introduced and integrated into existing systems, including new or altered protein factors and a corresponding gene regulatory network to make sure that the new could be assimilated into the old and work together in a concerted fashion. The long neck could become a possibly viable direction of evolution only if all these conditions could be satisfied at the same time. However such large scale changes must be of far-reaching nature and well beyond what mutations and gene recombination that natural selection refers to were able to bring about.

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If giraffes’ ancestor had a compelling need for a long neck to survive better, and natural selection did select animals with long necks over their shorter-necked fellows, the reality would be that giraffes’ ancestor wouldn’t be able to evolve and become long-necked giraffes simply because of the compelling need and natural selection. If you sincerely would like to give natural selection some credit in the evolution of giraffe’s long neck, what it did at its best was to check whether giraffes could survive in its natural habitat, not necessarily survive better when their necks were grew long. It’s obvious that nature won’t give you something just because you need it.

Attribution of evolution of giraffes’ long necks to natural selection stood on flimsy ground. Giraffes’ ancestor wouldn’t be the only mammal living in such a habitat. Why did only giraffes develop such a long neck, while other mammals like deer or antelope remained normal necked and have survived ever since? Didn’t those mammals need long necks in such a habitat to gain survival advantage? From survival point of view, an excessively large body size provides the animals with more survival disadvantages rather than advantages. A large physical body easily hinders its movement and reproduction and requires extra large food consumption to sustain normal life activity. All this seriously limits its population size and makes the animals more easily succumb to food shortage and natural disasters. Therefore, giraffes as a new species at the time of its appearance didn’t gain any survival and reproduction advantage over normal-necked animals except the banal advantage to eat leaves on tall trees. Even this advantage might not be sure if the trees in the ancient habitats weren’t really as tall as today. Natural selection can’t be a fact for the neck to become this long.

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Giraffes and its closet relative short-necked okapi diverged from their common ancestor about 11.5 million years ago, yet giraffes and okapi shared only about 20% identical proteins, attesting the great magnitude of genome changes during the evolution of giraffes. Giraffes appear in the fossil record around 4 million years ago. A time span of 7 million years seemed too short to endure the genetic changes of this grand scale that gave rise to giraffes that bear a long neck.

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Assume that giraffes shared a common normal necked ancestor with deer or antelope. One individual ancestor suffered from some mutations in a gene coding for a protein factor that guided neck muscle development. The mutations somehow altered its biochemical properties and guided neck muscle to grow longer. In other words, the appearance of giraffes as a new species was likely to be triggered initially by some random mutations of similar kinds. The giraffes’ neck development wasn’t a single event isolated only to the necks, but affected giraffes in its entirety. The giraffes had to mass a large number of proteins with new or altered properties to build up a phenotype – a long neck and everything else that came with the long neck. All genes coding for these proteins must first be made available, and then be linked together through regulatory elements that control their differential expression in different tissues. This process was so complicated and interlinked, requiring the greatest coordination and integration in a relatively short time, which occurred far beyond the control of natural pressures for the animals to eat leaves on tall trees. If overall changes to the genotype couldn’t support the long neck, which must be common during the process, giraffes could be deemed as biological defects and eliminated due to failure to grow, survive, or reproduce. A long neck would become inevitable if cardiovascular system, nervous system and other impacted systems could make sweeping changes to suit the long neck as a whole in one evolution cycle. It’s highly dubious that natural environments and habitats could play any roles in the evolution of giraffes.

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Modern research hasn’t shown something in nature that could direct an organism to change particular genes or mutate particular base pairs to gain desired beneficial traits. There is no mechanism through which an organism could be aware of which genes were involved in the evolution of a particular trait or engaged in a given biochemical process. All traits are developed through random changes in the genomes over long period of time, not due to any need for this or that kinds of traits. Organisms will accept any traits random mutations can bring about so long as the new traits are not lethal.

The best examples of evolution and natural selection came from Charles Darwin’s observations of bird finches in Galápagos islands. Finches’ bill sizes and shapes are attributed to each bird’s adaptation to a specific type of food on the islands. For example, a thick beak adapted to feeding on crunchy seeds and arthropods, while a slender, pointy bill to catching tasty insects hiding between the leaves, and twigs or cactus spines to prying arthropods out of holes on tree trunks. There are more examples to the list. Curlew’s long bill can probe deep into the mud and shallow water to catch aquatic invertebrates. Great egret’s long legs allow the birds to walk in relatively deep water to search for fishes.

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If we think a little more, it’s not difficult to realize that appearances of birds’ these highly specialized bills or legs in the course of evolution and their life styles are actually the chicken or the egg problem, a causality dilemma if you are stubborn enough to put them in order. A bird was considered to have developed long legs in order to adapt to deep water habitat, and developed a thick beak so it could feed on crunchy seeds and arthropods. There is an equally sound and even much more logic explanation. A bird had developed specialized bill or legs first. Because of the long legs, the birds gained the ability to enter the water and look for fish swimming in the water. This could be considered an active adaptation of the deep water habitat, in stead of nature forcing the birds to find food in the deep water for survival. Similarly because of the thick beak, the bird became able to feed on crunchy seeds and arthropods first, then they feed on crunchy seeds and arthropods as they are today.

Could natural force make a bird’s legs long or beak thick so that those birds could survive better? In the later explanation, natural selection was no more than a type of adaptation to the natural environment. It’s the birds that played active roles upon obtaining special traits that allowed them to adventure into a proper natural environment. A bird can’t control what kind of favorable traits it can have, but it can put whatever favorable traits it already has to practical uses by actively finding a natural environment that best fits those favorable traits.

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The active adaptation is more likely to be what has happened during billions of years of evolution. More examples could be found to support this view. Fish living in the dark cave is usually blind. It isn’t the darkness that makes the fish blind, instead it’s random mutations in the visual system that have caused fish blind, and blind fish could survive in the dark cave due to lack of predators there. Swimming is an ability beneficial to a mammal’s survival, but not all mammals can swim. The enormous body sizes of many dinosaurs shouldn’t be the result of natural selection to adapt to any natural environments. Excessively large antlers on some male deer could be detrimental to their survival when traced by their predators in dense woodland. Some traits are good, but not for every animal, while some traits are bad, but appear on some animals.

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On the Galápagos islands again, a completely new finch species was created in the wild in just two generations by mating of two different species of finches. The importance of this observation was over exaggerated. Mating between different species is not often. First different species don’t attract each other for mating. Second fertilization couldn’t occur due to recognition failure between an egg and a sperm. Third if fertilization succeeded, the hybrid offspring would carry two sets of proteins serving the same functions, but with different amino acid sequences, one from mother and one from father. These two sets of proteins were likely unable to interact with each other, thus disrupting normal biochemical processes and leading to the death of the hybrid organism. Fourth if hybrid offspring did develop normally, it was often sterile or reproduced with difficulty. If the hybrid offspring was able to reproduce, then it indicated that the two parent species were close enough for mating, and nothing more. It would not be scientific if the hybrid offspring was judged to be a new species just based on their appearance, food preferences, etc.

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Almost all organisms enjoy a sort of ability to tolerate the environmental changes big or small, and this ability is built in the genome. A lot of organisms would have gone extinction without tolerance for changes. Animals like rats can tolerate a broad range of environments and live all over the earth because their tolerance is exceptionally strong and lax, while animals like some amphibian species can survive only in niche space with ecologically strict conditions because their tolerance is poor and rigid. It seems unlikely that it was natural selection that made rats able to tolerate a variety of natural environments and some amphibians tolerate no environment outside their current habitats. Favorable traits in a population are sufficient to enable the population to adapt to different kinds of environments without selective pressure. Natural selection doesn’t seem to play much of a role in the evolution of species as it has been generally accepted in the scientific community.

Throughout the entire evolutionary course, natural environments had made profound impacts on the evolution of species through geologic and climate events. We learned natural selection from the basic biology classes, but what it really means could be misunderstood easily because of ambiguity caused by the word “natural”. Natural selection will preserve any traits that make individuals survive and reproduce better in the population. New species can result if new traits made the organisms too different from the traits seen on their predecessors. Natural selection can be easily understood as a determining force that moves evolution forward by putting natural pressure on the organisms to develop and adapt. To many, natural selection is the engine that drives evolution. But they forgot about the fact that there exists no feedback mechanism between phenotype and genotype. A good phenotype or trait can’t be made better simply by feeding back to the genome and asking for necessary changes to make me better.

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The importance of natural selection as a theory in modern biology doesn’t need to be emphasized more. However, can natural selection really explain evolution of species as it has been claimed for many many years? In free, natural habitats, individual organisms in the population carry more or less their own random heritable mutations, including mutations from DNA rearrangement. The phenotype of those mutations could be bad, neutral, or good, affecting more or less the survivability of the mutation carriers. Because mutations are of random nature, it is unknown what effect new mutations will have on the survivability of individuals, and the consequences are discrete beyond anyone’s control. Random genomic changes that were detrimental to mutation carriers were hardly able to survive beyond birth.

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Every object, living or non-living, has inherent properties that determine its behavior on the macro level. To a living organism, its behavior includes its special diet and unusual habitats. Why is it important to consider the behavior of organisms? The behavior determines what an organism will do to other individuals in the population and beyond and to natural environments as well. For organisms all this is encoded in their genomes. As a result, different organisms behave differently. Some organisms are quite hostile, even belligerent in behavior towards others, showing very competitive nature. Other are weak and seemingly vulnerable to natural predators, but they have been in existence ever since they emerged from the evolution. Special behaviors shield weak organisms from the dangerous food chain and survive in their own safe niches.

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In the free wildness, fierce competition, special behaviors, food preferences are the ultimate way to decide who will lead to differential survival and reproduction and dominate the population. Competition among individuals of same species or different species occurs spontaneously thanks to individuals’ behavior. By controlling the behavior of a species, evolution has devised a mechanism to preserve and pass down mutations that could be translated into a behavior that gave rise to advantage in survival. Individuals with better survivability would finally become dominant in the population. Evolution has conferred all types of behaviors to millions of species, allowing them to survive and even strive in a variety of environments that suit their behaviors. Because of this, there is tremendous biodiversity on the earth today. It must be emphasized that the appearance of any favorable mutations are not intentional, but out of random events on the genomes.

A trait in general is stable over time and has a quite complicated genotype behind. In an evolution cycle, a number of genes, newly created and variants of existing, must work together to engender new functionalities called traits. The new traits are always part of new species, and could impact the survival of new species in terms of food and natural predators. New species would perish from diet scarcity or increased risk of natural predators in the old habitats, unless they were able to migrate to places where food was ample and natural predators wouldn’t endanger their existence. The appearance of a new trait wasn’t necessarily to benefit the species to inhabit its native environment, rather it could be a rational way to disseminate the living organisms across lands and settle in different territories.

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For example, the ancestor of giant pandas might be a mammal indigenous to an area where bamboo wasn’t a widespread plant species. During the evolution, panda developed a unique digestive system that contained taste buds for bamboo and was equipped with teeth that could chew bamboo, and stomach that could digest bamboo. Such a peculiar digestive system prompted giant panda to migrate from its native habitat to places where bamboo was abundant. From genetic point of view, panda genome determines bamboo as its major diet, and bamboo diet in turn determines what kind of behavior panda will exhibit. It’s panda’s special behavior that prompted panda to select bamboo rich terrain to be its native habitat. A narrow appetite for bamboo put panda in a grave disadvantageous situation for its survival, but it can’t be changed through natural selection. It isn’t happening that a trait can be changed simply because it isn’t a good one.