A few definitions from the blog:
1) The original front-loaded state had sufficient information that would bias evolutionary trajectories needed to evolve complex, multicellular organisms.
2) Front-loading assumes that life began with a consortium of different genomes that, as a communicating group, contained sufficient information needed to bias evolutionary trajectories needed to evolve complex, multi-cellular organisms.
3) Front-loading does NOT predict we should find genes that serve no apparent purpose until the new function (in this case multicellularity) arises.
Other people also have interesting ideas that are friendly to the idea of FLE. Michael Sherman in his article about the Universal Genome in the Origin of Metazoa proposes the following:
We observe ultraconserved, ultraselected sequences with no apparent effect on fitness of the organism. The four sequences that were knocked out in this study had no visible immediate effect on fitness in the mice. Interestingly, one of the sequences (uc467) is found in the reptile, Carolina anole. Use this site to blast the uc467 sequence in eukatyotes. It would be interesting to see what the function of this sequence is in the Carolina anole genome and whether deletion of the sequence will have any effect on fitness.
It is thus not inconceivable that some of the sequences in the proposed Universal Genome in the Origin of Metazoa might have no immediate effect on fitness, but still have a function by acting as a reservoir of genetic material on which variation inducing mechanisms such as sequence duplication, somatic hypermutation, gene conversion and homologous recombination can act upon during periods of selection. Intracellular quality control mechanisms then act as selection mechanisms to keep the sequences in tact, be it as a result of a redundant mechanism or an EAM mechanism.
Thus, from a FLE (and EAM?) perspective, ultraconserved sequences of DNA (and other sequences) that do not have any effect on immediate fitness might function as a reservoir of information for future adaptation whereby the intelligent systems within cells can act upon and use during times of selection. In this way the two views might be reconciled whereby sequences with no effect on fitness still biases evolutionary trajectories because of the intelligent use of "functionless" sequences.
From a FLE and EAM perspective, instead of viewing cells as passive entities whereby random mutations (and other mechanisms) introduce variety for no reason on which natural selection blindly acts upon with regards to fitness, why not view cells as active entities that search random space for solutions during times of selection pressure. The intrinsic quality control systems can also be seen to act as selection mechanisms to constrain the random search and thus bias the output of a random search.
Is this view tenable? Evidence for evolution from a front-loaded state?
1) The universal genetic code seems to be optimized for random searches:
1) The original front-loaded state had sufficient information that would bias evolutionary trajectories needed to evolve complex, multicellular organisms.
2) Front-loading assumes that life began with a consortium of different genomes that, as a communicating group, contained sufficient information needed to bias evolutionary trajectories needed to evolve complex, multi-cellular organisms.
3) Front-loading does NOT predict we should find genes that serve no apparent purpose until the new function (in this case multicellularity) arises.
Other people also have interesting ideas that are friendly to the idea of FLE. Michael Sherman in his article about the Universal Genome in the Origin of Metazoa proposes the following:
1) first that a significant fraction of genetic information in lower taxons must be functionally useless but becomes useful in higher taxonsThese propositions are in contrast to the third definition from Mike Gene's blog, however they might not be mutually exclusive. Here is how:
2) Second, that one should be able to turn on in lower taxons some of the complex latent developmental programs, e.g., a program of eye development or antibody synthesis in sea urchin.
We observe ultraconserved, ultraselected sequences with no apparent effect on fitness of the organism. The four sequences that were knocked out in this study had no visible immediate effect on fitness in the mice. Interestingly, one of the sequences (uc467) is found in the reptile, Carolina anole. Use this site to blast the uc467 sequence in eukatyotes. It would be interesting to see what the function of this sequence is in the Carolina anole genome and whether deletion of the sequence will have any effect on fitness.
It is thus not inconceivable that some of the sequences in the proposed Universal Genome in the Origin of Metazoa might have no immediate effect on fitness, but still have a function by acting as a reservoir of genetic material on which variation inducing mechanisms such as sequence duplication, somatic hypermutation, gene conversion and homologous recombination can act upon during periods of selection. Intracellular quality control mechanisms then act as selection mechanisms to keep the sequences in tact, be it as a result of a redundant mechanism or an EAM mechanism.
Thus, from a FLE (and EAM?) perspective, ultraconserved sequences of DNA (and other sequences) that do not have any effect on immediate fitness might function as a reservoir of information for future adaptation whereby the intelligent systems within cells can act upon and use during times of selection. In this way the two views might be reconciled whereby sequences with no effect on fitness still biases evolutionary trajectories because of the intelligent use of "functionless" sequences.
From a FLE and EAM perspective, instead of viewing cells as passive entities whereby random mutations (and other mechanisms) introduce variety for no reason on which natural selection blindly acts upon with regards to fitness, why not view cells as active entities that search random space for solutions during times of selection pressure. The intrinsic quality control systems can also be seen to act as selection mechanisms to constrain the random search and thus bias the output of a random search.
Is this view tenable? Evidence for evolution from a front-loaded state?
1) The universal genetic code seems to be optimized for random searches:
- They (Itzkovitz and Alon) compared the actual genetic code with an ensemble of all other codes that are equally optimized with respect to mistranslation or mutation. (Bollenbach et al. (2007))
- Itzkovitz and Alon suggest another, quite unanticipated, type of optimality: the code is highly optimal for encoding arbitrary additional information, i.e., information other than the amino acid sequence in protein-coding sequences. (Bollenbach et al. (2007))
- The effect of cytosine deamination on a random pool of amino acids facilitates evolution. (Link)
- Cytosine deamination also does not result in any stop codon formation. (Link)
2) Variation inducers:
The optimal features of the genetic code allows it to be exploited to generate controlled variety. Take the immune system as an example:
Antibody diversification is crucial in limiting the frequency of environmentally acquired infections and thereby increasing the fitness of the organism. Initial diversification of antibodies is achieved by assembling variable (V), diversity (D) and joining (J) gene segments (V(D)J recombination) by non-homologous recombination. Further diversification is carried out by somatic hypermutation (SHM) and Class Switch Recombination. Central to the initiation to these diversification processes is the activation-induced cytosine deaminase (AID) protein. AID deaminates cytosine to uracil in single stranded DNA (ssDNA - arising during gene transcription) and is dependent on active gene transcription of the various antibody genes. The induced mutation is resolved by at least 4 pathways (Figure 4):
1) Copying of the base by high-fidelity polymerases during DNA replication.
2) Short-Patch Base Excision Repair (SP-BER) by uracil-DNA glycosylase removal and subsequent repair of the base.
3) Long-Patch Base Excision Repair (LP-BER)
4) Mismatch repair (MMR)
The activity and gene expression of AID is controlled. The type of error-repair pathway and the subsequent recruitment of various low-fidelity polymerases determine the type of mutations after the repair process and these also seem to be controlled. Current research focuses on the mechanisms of control of downstream repair pathways and why this system is selectively targeted to the small region of antibody genes.
Thus, the immune system exploits the optimal properties the genetic code for the purpose of controlled variability. Is the system limited to vertabrates or can similar systems be found in other organisms. Cytosine deamninases are found in bacteria as well. Error-prone (low-fidelity) repair systems are also present. Will we discover an active system in bacteria that exploits the properties of the genetic code for the purpose of controlled variability under selective pressure? Will RecA (An evolution gene) and LexA play a part?
Thus, variation inducers facilitate evolution by making use of random variation to generate variability.
3) Quality control systems (Intrinsic selection systems)
Cell division in all the domains of life is under extreme control in order to ensure daughter cells have sufficient machinery to repeat the process. Cell division is a highly regulated process with various positive- and negative-feedback systems. Quality control mechanisms during various stages of cell division monitor the fidelity of the process. Whenever the events during cell division leads to faulty cell division, another program is activated to remove the faulty cell from the population through programmed cell death (apoptosis, autophagy, metabolic catastrophy, necrosis etc.). Programmed cell death is a process found in multicelullar as well as unicellular organisms and can be activated through a variety of signaling networks.
Protein quality control mechanisms are also found in uni- and multicelular organisms. Sometimes, even functional mutated proteins get removed from the population of proteins generated in the genome. Thus this serve to constrain evolution, preventing certain functional proteins from entering a population.
Quality control systems would thus facilitate in constraining (biasing) evolution, putting it under intrinsic control.
What about the front-loaded state?
A) How far back into the history of life can we go to posit a front-loaded state?
Various trees of life exist, however the revised tree of life from Doolittle is probably our best understanding at present (HT: Zachriel). Where on that tree of life did life start to harness random variation for controlled variability?
It is probably best to view the front-loaded state to be at position A.
B) What does the front-loaded state consist of?
Figure 2: Components of a front-loaded state
Components of the front-loaded can be viewed as those components that are ubiquitous components of various life forms at present. These include:
Optimized genetic code
Cell division machinery (replisome)
Variation inducers (Cytosine deaminase)
Quality control mechanisms (chaperones, programmed cell death)
C) Does the front-loaded state have to have any metaphysical implications?
Not necessarily. A front-loaded state can still be viewed to be the result of random variation and selection. All that needs to be determined is to find a plausible route(s) to the perceived front-loaded state and an explanation why natural selection during abiogenesis was so strong to lead to only one front-loaded state and not the sundry of other possibilities (Figure 2), and why a front-loaded state is able to bias evolutionary trajectories.
All-in-all, the FLE and EAM hypotheses, together with the observations of biomolecular machines, convergent evolution, the possible connection between quantum physics and consciousness and the possibility that evolution is exploring pre-existing realities, provide a powerful teleological framework for looking at the evolution of life. And then there are the surprises waiting to be discovered in the sequenced genomes of primitive eukaryotes.
The optimal features of the genetic code allows it to be exploited to generate controlled variety. Take the immune system as an example:
Antibody diversification is crucial in limiting the frequency of environmentally acquired infections and thereby increasing the fitness of the organism. Initial diversification of antibodies is achieved by assembling variable (V), diversity (D) and joining (J) gene segments (V(D)J recombination) by non-homologous recombination. Further diversification is carried out by somatic hypermutation (SHM) and Class Switch Recombination. Central to the initiation to these diversification processes is the activation-induced cytosine deaminase (AID) protein. AID deaminates cytosine to uracil in single stranded DNA (ssDNA - arising during gene transcription) and is dependent on active gene transcription of the various antibody genes. The induced mutation is resolved by at least 4 pathways (Figure 4):
1) Copying of the base by high-fidelity polymerases during DNA replication.
2) Short-Patch Base Excision Repair (SP-BER) by uracil-DNA glycosylase removal and subsequent repair of the base.
3) Long-Patch Base Excision Repair (LP-BER)
4) Mismatch repair (MMR)
The activity and gene expression of AID is controlled. The type of error-repair pathway and the subsequent recruitment of various low-fidelity polymerases determine the type of mutations after the repair process and these also seem to be controlled. Current research focuses on the mechanisms of control of downstream repair pathways and why this system is selectively targeted to the small region of antibody genes.
Thus, the immune system exploits the optimal properties the genetic code for the purpose of controlled variability. Is the system limited to vertabrates or can similar systems be found in other organisms. Cytosine deamninases are found in bacteria as well. Error-prone (low-fidelity) repair systems are also present. Will we discover an active system in bacteria that exploits the properties of the genetic code for the purpose of controlled variability under selective pressure? Will RecA (An evolution gene) and LexA play a part?
Thus, variation inducers facilitate evolution by making use of random variation to generate variability.
3) Quality control systems (Intrinsic selection systems)
Cell division in all the domains of life is under extreme control in order to ensure daughter cells have sufficient machinery to repeat the process. Cell division is a highly regulated process with various positive- and negative-feedback systems. Quality control mechanisms during various stages of cell division monitor the fidelity of the process. Whenever the events during cell division leads to faulty cell division, another program is activated to remove the faulty cell from the population through programmed cell death (apoptosis, autophagy, metabolic catastrophy, necrosis etc.). Programmed cell death is a process found in multicelullar as well as unicellular organisms and can be activated through a variety of signaling networks.
Protein quality control mechanisms are also found in uni- and multicelular organisms. Sometimes, even functional mutated proteins get removed from the population of proteins generated in the genome. Thus this serve to constrain evolution, preventing certain functional proteins from entering a population.
Quality control systems would thus facilitate in constraining (biasing) evolution, putting it under intrinsic control.
What about the front-loaded state?
A) How far back into the history of life can we go to posit a front-loaded state?
Various trees of life exist, however the revised tree of life from Doolittle is probably our best understanding at present (HT: Zachriel). Where on that tree of life did life start to harness random variation for controlled variability?
Figure 1: Doolittle tree of life with proposed front-loaded states
It is probably best to view the front-loaded state to be at position A.
B) What does the front-loaded state consist of?
Figure 2: Components of a front-loaded stateComponents of the front-loaded can be viewed as those components that are ubiquitous components of various life forms at present. These include:
Optimized genetic code
Cell division machinery (replisome)
Variation inducers (Cytosine deaminase)
Quality control mechanisms (chaperones, programmed cell death)
C) Does the front-loaded state have to have any metaphysical implications?
Not necessarily. A front-loaded state can still be viewed to be the result of random variation and selection. All that needs to be determined is to find a plausible route(s) to the perceived front-loaded state and an explanation why natural selection during abiogenesis was so strong to lead to only one front-loaded state and not the sundry of other possibilities (Figure 2), and why a front-loaded state is able to bias evolutionary trajectories.
All-in-all, the FLE and EAM hypotheses, together with the observations of biomolecular machines, convergent evolution, the possible connection between quantum physics and consciousness and the possibility that evolution is exploring pre-existing realities, provide a powerful teleological framework for looking at the evolution of life. And then there are the surprises waiting to be discovered in the sequenced genomes of primitive eukaryotes.
0 comments:
Post a Comment