An edited version of ideas posted earlier, please bear with the length...
Integral Theory of Evolution
“God created man in His own image, and behold, it was very good. And the evening and the morning were the sixth day.”
-GENESIS 1.27, 31
“If there is one thing the history of evolution has taught us it's that life will not be contained. Life breaks free, expands to new territory, and crashes through barriers, painfully, maybe even dangerously.”
-Michael Creighton (Jurassic Park)
Note: The writing in the following sections is meant to accommodate the reader; I do not mean to ascribe any sort of consciousness to genes.
Not too long ago, biochemists proclaimed an end to cancer after the initial success of the drug imatinib in the selective elimination of certain types of leukemia via inhibition of mutant tyrosine kinases. Their joy, however, was short lived.
Bacterial cells and viruses are able to quickly develop resistance to antibiotics because they divide rapidly and their rate of genetic mutations and subsequently evolution is much more rapid than multicellular organisms with large, complex macrogenomes. More specifically they’re able to quickly vary their genotypes. Thus via natural selection and other driving sources they are able to correct their genetic weaknesses that antibiotics target; predominantly by sheer chance resulting from brute force tactics (similar to a hacker entering every possible arrangement of letters into a computer until he finds the password). Tumor cells can behave in a very similar manner. Tumor cells also divide rapidly (it is actually their rapid rate of division that makes chemotherapy an option) and the same scenario develops. The renegade genetic strain ‘recognizes’ that imatinib is taking it down and corrects for it via Darwinian evolution; resulting in an imatinib resistance and thus the need for researchers to develop new drugs. This is amazing. The genes behind cancer are no exception to my ideas that every gene species possess a drive to survive. Once the genetic strain has mutated into a cancer cell, it has, in my opinion become a sort of subspecies of the human genome. The human genome eventually recognizes this and attempts everything within its limit to destroy the cell. In a perfect world, the tumor strain would allow its destruction for the betterment of the species of a whole. But it doesn’t. It is its own species, and it does not want to die. Thus it divides as quickly as possible to prevent its extinction and gain a numerical edge, and sends out colonizers throughout the blood stream to establish a presence. All of these actions often result in the death of the host and subsequently the gene. Thus it is a tragic destiny, a depressing story for the gene with only one ending. It is a microcosal example of perhaps a hostage taker trying to make it out alive.
As novelist Michael Creighton reiterates above, life and thus genetics, tends to eventually find a way. Thus it is plausible that an oncogene might somehow derive a mechanism to excise itself from its host genome and maybe even escape the cell. One possible method to export a genetic sequence from the cell would be through an ancient vector, mRNA. This would require much outside help. For one there would need to be a large variety of enzymes, some of the more important ones being proteases, integrases, and, the most crucial, reverse transcriptase to transcribe the sequence from RNA to DNA in order to recreate the genome after escaping. But the tools are there. Proteases are fairly common throughout the average cell while integrase is very similar to proteins used in post-transcriptional modification in eukaryotes. But what of reverse transcriptase? It is there as well. Recent studies show that cancerous cells show excessive telomerase activity, an enzyme used to create repetitive ‘buffer zones’ at chromosomal ends to prevent a progressive degradation during replication. This is important because one of the subunits of telomerase is none other than a form of reverse transcriptase. Suppose an oncogene managed to utilize these resources to successfully convert into mRNA, might it then have been able to escape via a primitive vector such as a piece of membrane from the host cell? If so, could it reintegrate itself into a separate host as does a virus?
If this were the case, we would expect to see a class of viruses whose genetic material consists of mRNA and causes cancer like symptoms when integrated into a new host. Say hello to the retrovirus. Although most renowned as the causal agent of AIDS, retroviruses are responsible for a wide variety of diseases in many mammalian species. Interestingly enough, the majority of these diseases associated with them are cancers such as sarcomas and leukemia. Therefore it is possible that retroviruses are not as ancient as biologists once assumed, but rather a product of the eukaryotic genome. Of course it is also possible that modern retroviruses picked up the necessary equipment for their escape left behind in our systems by endogenous retroviruses.
The fact of the matter is that retroviruses are not unique. Genetic elements are continuously removing themselves and re-integrating into our genomes in the forms of transposons, DNA viruses, RNA viruses, endogenous retroviruses, naked DNA and so on. Our genome, along with the genome of every other complex organism (i.e. not viruses) is not a steady code but rather a dynamic population with elements immigrating, emigrating, and mutating at a steady rate. The sum of these actions, supplemented by Darwinian factors, culminates in the driving force of evolution.
A close inspection of our genome reveals a dynamic world populated by mobile sequences of nucleic acids. It is the result of millions of years of addition, subtraction, and competition amongst these sequences that has made our DNA the way it is today. The integrative theory of evolution is the idea that the act of combining differentiated genetic sequences which are preceded and followed by Darwinian evolution is the rate determining step in the development of complex metabolic machinery and anatomic structures. The integrative theory of evolution is very hard for me to sum up in a single sentence so instead I will attempt to do so through a simplified timeline of how I believe our genomes came to be what they are today.
I believe that initially there was RNA. I do not know how or why it came to be I just postulate that it was the first of the nucleic acids. RNA, once synthesized and differentiated into various forms by whatever means, had an amazing ability. It could manipulate its chemical environment through the production of proteins. The more proteins that were created, the more resources that could be utilized by the RNA for construction of additional proteins or other biomolecules such as lipids, sugars, etc. As these RNA’s consumed and produced more and more, they developed to such complexity that they could be viewed as a proto-organism. However, a single RNA sequence can only form so many proteins, and thus different RNA sequences found interdependence to be a survival advantage in that they could each benefit off of each other’s specific proteins. This development led to the first colonial RNA proto-organisms. This presented a problem however, as all proteins being expressed from all RNA sequences at once would lead to chemical chaos and ill fortune to the colony as a whole. It thus became necessary to find a way to organize the sequences into a system by which only certain factors would be expressed at once through the help of outside proteins. Through simple redox chemistry, the first DNA sequences were born. These sequences were in fact incorporated populations of different factions. As the sequences and necessarily the biomolecular structures surrounding, nourishing, and maintaining them became more and more complex with the integration of more and more stray sequences, complex biochemical pathways became a necessity. As these genomes grew in size, various factions began to fight for expression by multiplying or translocating themselves within the sequence. This natural competition, Darwinian in nature, lead to increasing specificity among different genomes as certain factions gained a survival advantage over others and dominated parts of the genome. Also complexity began to increase as more sequences entered the genome. The end results were the first prokaryotic cells, now with complex mechanisms for integrating new DNA (transformation and conjugation) and also affected by the constant immigration and emigration of various genetic elements through transduction and viral escape respectively. The power of the combined actions of the dynamic genetic populations within genomes to induce evolution I will for now on refer to as integral forces.
It did not stop there. Following suit of the genetic elements within them, prokaryotic cells found survival advantage in numbers and thus the first multicellular colonial organisms were formed. Eventually barriers between individual cells were broken down and genomes combined through integration into macrogenomes. The result was the first truly eukaryotic cell. As a further mechanism of controlling the actions of so many different factions, sequences which no longer expressed proteins relevant to the community to the whole were inhibited by a new system of post-transcriptional modification; splicing. These eukaryotes began to move into the vastly different directions that integral forces took them and differentiated into the various forms we see today, one of which is man. These genetic populations continued to compete for expression and thus resources amongst each other, leading to the synthesis of complex ecosystems. Other transient sequences evolved into obligate parasites and made use of occasional chemical mistakes, Darwin’s random mutations, to evade the biological defenses of the far more complex macrogenomes they infected; leading to the first viruses.
The evidence that our genomes are a collection of smaller ones is there. We still hold the genes which transcribe features of earlier organisms, such as skeletal structures or organs, within our DNA. Occasionally these sequences proliferate throughout our genome and evade splicing, thus managing to be expressed in the form of vestiges.
Also, integrative evolution was an essential innovation for the development of our adaptive immune systems. The genomes of stem cells for T and B cells as well as the genes encoding for antibodies are all initially the same as the result of the integration of thousands of different types. However, in order to be functional, only one type of B-cell, T-cell, or antibody can exist for a specific antigen. To account for this, stem cell precursors 'de-integrate' themselves by removing vast amounts of DNA, resulting in a specific genome different from those present in other cells in the body. For antibodies, mRNA is heavily spliced to ensure that only one type is made. This phenomenon of alternative splicing can be applied to a wide variety of eukaryotic proteins.
In fact, any sort of cell must silence the many other incorporated sequences within its code during development. This way, only some factions are granted expression and the cell is allowed to differentiate into a form suitable for its primary function.
The sum of this theory is that it is the integral forces that play a large part in evolution. Darwinian evolution is there, and it is indeed responsible for important changes, such as those seen in sickle cell anemia and antimalarial resistance. However, it runs parallel and is arguably less profound than integration, with the exception being in organisms with smaller genomes such as viruses. Often, Darwinian factors will precede and follow an act of integrative evolution. This can be seen in the evolution of various complex structures such as eyes. The integral step was needed to make the jump from ‘eye spots’ seen in unicellular organisms to the wide variety of eyes seen in multicellular organisms.
This idea of integration repeats itself through the complexity of biology. Early RNA factions grouped together and integrated to form the first DNA sequences, which grouped together and integrated into the first prokaryotes, which grouped together and integrated into the first eukaryotes. Even in society we see how our genes influence social interactions. The first people grouped together to form communities which grouped together to form towns, nations, and empires. Economies find greater wealth when differentiated cells become interdependent, colonize, and integrate as was seen in America and is currently happening in the European Union. In fact, global society today appears to be a possible macrocosm of our genomes, bringing home the idea that we are what out genes make us.
Nucleic acids still utilize and manipulate the resources of their environment, in one particular strain they do so through a system of complex biological structures collectively known as man, which is the result of an ordered expression of RNA sequences leading to the production of various proteins. It is eerie to note that we are a manifestation of our genes, made in their own images, one might conclude.
Integral Theory of Evolution
“God created man in His own image, and behold, it was very good. And the evening and the morning were the sixth day.”
-GENESIS 1.27, 31
“If there is one thing the history of evolution has taught us it's that life will not be contained. Life breaks free, expands to new territory, and crashes through barriers, painfully, maybe even dangerously.”
-Michael Creighton (Jurassic Park)
Note: The writing in the following sections is meant to accommodate the reader; I do not mean to ascribe any sort of consciousness to genes.
Not too long ago, biochemists proclaimed an end to cancer after the initial success of the drug imatinib in the selective elimination of certain types of leukemia via inhibition of mutant tyrosine kinases. Their joy, however, was short lived.
Bacterial cells and viruses are able to quickly develop resistance to antibiotics because they divide rapidly and their rate of genetic mutations and subsequently evolution is much more rapid than multicellular organisms with large, complex macrogenomes. More specifically they’re able to quickly vary their genotypes. Thus via natural selection and other driving sources they are able to correct their genetic weaknesses that antibiotics target; predominantly by sheer chance resulting from brute force tactics (similar to a hacker entering every possible arrangement of letters into a computer until he finds the password). Tumor cells can behave in a very similar manner. Tumor cells also divide rapidly (it is actually their rapid rate of division that makes chemotherapy an option) and the same scenario develops. The renegade genetic strain ‘recognizes’ that imatinib is taking it down and corrects for it via Darwinian evolution; resulting in an imatinib resistance and thus the need for researchers to develop new drugs. This is amazing. The genes behind cancer are no exception to my ideas that every gene species possess a drive to survive. Once the genetic strain has mutated into a cancer cell, it has, in my opinion become a sort of subspecies of the human genome. The human genome eventually recognizes this and attempts everything within its limit to destroy the cell. In a perfect world, the tumor strain would allow its destruction for the betterment of the species of a whole. But it doesn’t. It is its own species, and it does not want to die. Thus it divides as quickly as possible to prevent its extinction and gain a numerical edge, and sends out colonizers throughout the blood stream to establish a presence. All of these actions often result in the death of the host and subsequently the gene. Thus it is a tragic destiny, a depressing story for the gene with only one ending. It is a microcosal example of perhaps a hostage taker trying to make it out alive.
As novelist Michael Creighton reiterates above, life and thus genetics, tends to eventually find a way. Thus it is plausible that an oncogene might somehow derive a mechanism to excise itself from its host genome and maybe even escape the cell. One possible method to export a genetic sequence from the cell would be through an ancient vector, mRNA. This would require much outside help. For one there would need to be a large variety of enzymes, some of the more important ones being proteases, integrases, and, the most crucial, reverse transcriptase to transcribe the sequence from RNA to DNA in order to recreate the genome after escaping. But the tools are there. Proteases are fairly common throughout the average cell while integrase is very similar to proteins used in post-transcriptional modification in eukaryotes. But what of reverse transcriptase? It is there as well. Recent studies show that cancerous cells show excessive telomerase activity, an enzyme used to create repetitive ‘buffer zones’ at chromosomal ends to prevent a progressive degradation during replication. This is important because one of the subunits of telomerase is none other than a form of reverse transcriptase. Suppose an oncogene managed to utilize these resources to successfully convert into mRNA, might it then have been able to escape via a primitive vector such as a piece of membrane from the host cell? If so, could it reintegrate itself into a separate host as does a virus?
If this were the case, we would expect to see a class of viruses whose genetic material consists of mRNA and causes cancer like symptoms when integrated into a new host. Say hello to the retrovirus. Although most renowned as the causal agent of AIDS, retroviruses are responsible for a wide variety of diseases in many mammalian species. Interestingly enough, the majority of these diseases associated with them are cancers such as sarcomas and leukemia. Therefore it is possible that retroviruses are not as ancient as biologists once assumed, but rather a product of the eukaryotic genome. Of course it is also possible that modern retroviruses picked up the necessary equipment for their escape left behind in our systems by endogenous retroviruses.
The fact of the matter is that retroviruses are not unique. Genetic elements are continuously removing themselves and re-integrating into our genomes in the forms of transposons, DNA viruses, RNA viruses, endogenous retroviruses, naked DNA and so on. Our genome, along with the genome of every other complex organism (i.e. not viruses) is not a steady code but rather a dynamic population with elements immigrating, emigrating, and mutating at a steady rate. The sum of these actions, supplemented by Darwinian factors, culminates in the driving force of evolution.
A close inspection of our genome reveals a dynamic world populated by mobile sequences of nucleic acids. It is the result of millions of years of addition, subtraction, and competition amongst these sequences that has made our DNA the way it is today. The integrative theory of evolution is the idea that the act of combining differentiated genetic sequences which are preceded and followed by Darwinian evolution is the rate determining step in the development of complex metabolic machinery and anatomic structures. The integrative theory of evolution is very hard for me to sum up in a single sentence so instead I will attempt to do so through a simplified timeline of how I believe our genomes came to be what they are today.
I believe that initially there was RNA. I do not know how or why it came to be I just postulate that it was the first of the nucleic acids. RNA, once synthesized and differentiated into various forms by whatever means, had an amazing ability. It could manipulate its chemical environment through the production of proteins. The more proteins that were created, the more resources that could be utilized by the RNA for construction of additional proteins or other biomolecules such as lipids, sugars, etc. As these RNA’s consumed and produced more and more, they developed to such complexity that they could be viewed as a proto-organism. However, a single RNA sequence can only form so many proteins, and thus different RNA sequences found interdependence to be a survival advantage in that they could each benefit off of each other’s specific proteins. This development led to the first colonial RNA proto-organisms. This presented a problem however, as all proteins being expressed from all RNA sequences at once would lead to chemical chaos and ill fortune to the colony as a whole. It thus became necessary to find a way to organize the sequences into a system by which only certain factors would be expressed at once through the help of outside proteins. Through simple redox chemistry, the first DNA sequences were born. These sequences were in fact incorporated populations of different factions. As the sequences and necessarily the biomolecular structures surrounding, nourishing, and maintaining them became more and more complex with the integration of more and more stray sequences, complex biochemical pathways became a necessity. As these genomes grew in size, various factions began to fight for expression by multiplying or translocating themselves within the sequence. This natural competition, Darwinian in nature, lead to increasing specificity among different genomes as certain factions gained a survival advantage over others and dominated parts of the genome. Also complexity began to increase as more sequences entered the genome. The end results were the first prokaryotic cells, now with complex mechanisms for integrating new DNA (transformation and conjugation) and also affected by the constant immigration and emigration of various genetic elements through transduction and viral escape respectively. The power of the combined actions of the dynamic genetic populations within genomes to induce evolution I will for now on refer to as integral forces.
It did not stop there. Following suit of the genetic elements within them, prokaryotic cells found survival advantage in numbers and thus the first multicellular colonial organisms were formed. Eventually barriers between individual cells were broken down and genomes combined through integration into macrogenomes. The result was the first truly eukaryotic cell. As a further mechanism of controlling the actions of so many different factions, sequences which no longer expressed proteins relevant to the community to the whole were inhibited by a new system of post-transcriptional modification; splicing. These eukaryotes began to move into the vastly different directions that integral forces took them and differentiated into the various forms we see today, one of which is man. These genetic populations continued to compete for expression and thus resources amongst each other, leading to the synthesis of complex ecosystems. Other transient sequences evolved into obligate parasites and made use of occasional chemical mistakes, Darwin’s random mutations, to evade the biological defenses of the far more complex macrogenomes they infected; leading to the first viruses.
The evidence that our genomes are a collection of smaller ones is there. We still hold the genes which transcribe features of earlier organisms, such as skeletal structures or organs, within our DNA. Occasionally these sequences proliferate throughout our genome and evade splicing, thus managing to be expressed in the form of vestiges.
Also, integrative evolution was an essential innovation for the development of our adaptive immune systems. The genomes of stem cells for T and B cells as well as the genes encoding for antibodies are all initially the same as the result of the integration of thousands of different types. However, in order to be functional, only one type of B-cell, T-cell, or antibody can exist for a specific antigen. To account for this, stem cell precursors 'de-integrate' themselves by removing vast amounts of DNA, resulting in a specific genome different from those present in other cells in the body. For antibodies, mRNA is heavily spliced to ensure that only one type is made. This phenomenon of alternative splicing can be applied to a wide variety of eukaryotic proteins.
In fact, any sort of cell must silence the many other incorporated sequences within its code during development. This way, only some factions are granted expression and the cell is allowed to differentiate into a form suitable for its primary function.
The sum of this theory is that it is the integral forces that play a large part in evolution. Darwinian evolution is there, and it is indeed responsible for important changes, such as those seen in sickle cell anemia and antimalarial resistance. However, it runs parallel and is arguably less profound than integration, with the exception being in organisms with smaller genomes such as viruses. Often, Darwinian factors will precede and follow an act of integrative evolution. This can be seen in the evolution of various complex structures such as eyes. The integral step was needed to make the jump from ‘eye spots’ seen in unicellular organisms to the wide variety of eyes seen in multicellular organisms.
This idea of integration repeats itself through the complexity of biology. Early RNA factions grouped together and integrated to form the first DNA sequences, which grouped together and integrated into the first prokaryotes, which grouped together and integrated into the first eukaryotes. Even in society we see how our genes influence social interactions. The first people grouped together to form communities which grouped together to form towns, nations, and empires. Economies find greater wealth when differentiated cells become interdependent, colonize, and integrate as was seen in America and is currently happening in the European Union. In fact, global society today appears to be a possible macrocosm of our genomes, bringing home the idea that we are what out genes make us.
Nucleic acids still utilize and manipulate the resources of their environment, in one particular strain they do so through a system of complex biological structures collectively known as man, which is the result of an ordered expression of RNA sequences leading to the production of various proteins. It is eerie to note that we are a manifestation of our genes, made in their own images, one might conclude.
