Tuesday, December 04, 2007

TR Gregory on Junk DNA

 
Ryan Gregory has posted another interesting discussion about junk DNA [Genome size, code bloat, and proof-by-analogy.]. You should read the entire article but I want to comment briefly on two important points.

Computer simulations rarely tell us anything about real biology in spite of the fact that computer scientists think otherwise. The main problems with most simulations is that they assume a pre-defined goal and they usually don't model random genetic drift and other non-adaptation events.

The second point is ...
Finally, it is essential to note that "non-coding elements make future evolution possible" explanations, though invoked by an alarming number of genome biologists, contradict basic evolutionary principles.


14 comments :

  1. "non-coding elements make future evolution possible"

    ??? That is NOT false; what would be false would be to say that noncoding elements ALONE make evolution possible (indeed a popular yet false "new trend9") Yet they certainly have a potential to become funtional; for instance, micro RNA 's do not code proteins but have the potential to turn gene expression on or off

    ReplyDelete
  2. Sanders--

    If you read my article you will see that you're missing the issue. It's not that non-coding elements don't contribute to evolutionary diversification. It's that this by itself cannot explain their existence in the genome.

    ReplyDelete
  3. If it is the really true that:

    tr gregory:
    Natural selection cannot favour a feature, especially a potentially costly one such as the presence of large amounts of non-coding DNA, because it may be useful down the line. Selection occurs in the here and now, and is based on reproductive success relative to competing alternatives.

    I'd like an explanation for how this is consistent with with data on (for example) the replicative fidelity of the poliovirus RNA polymerase (recall that polio uses an RNA genome). Data from the lab of Raul Andino at UCSF shows that either a decrease or an increase in the fidelity of the polymerase is associated with a loss of fitness. How can there be a loss of fitness associated with increased polymerase fidelity unless there is an advantage to the ability to generate mutations that although not currently necessary for growth, might someday be useful?

    ReplyDelete
  4. Inter-lineage selection versus just in case

    A virus, which exists in multiple lineages that are under strong selection by host immunity, falls into this category.

    Lineages that have more variability but are also not low-fidelity survive host immunity and persist. The rapid timescale at which this happens does not change what is going on fundamentally. Moreover, there could be another trait affected by the mutation -- you didn't give a citation so I haven't been able to discuss details.

    ReplyDelete
  5. Nevermind, I suspect this is what you are referring to.

    Vignuzzi, M., Stone, J.K, Arnold, J.J., Cameron, C.E., & Andino, R. 2006. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344-348.


    Abstract
    An RNA virus population does not consist of a single genotype; rather, it is an ensemble of related sequences, termed quasispecies(1-4). Quasispecies arise from rapid genomic evolution powered by the high mutation rate of RNA viral replication(5-8). Although a high mutation rate is dangerous for a virus because it results in nonviable individuals, it has been hypothesized that high mutation rates create a 'cloud' of potentially beneficial mutations at the population level, which afford the viral quasispecies a greater probability to evolve and adapt to new environments and challenges during infection(4,9-11). Mathematical models predict that viral quasispecies are not simply a collection of diverse mutants but a group of interactive variants, which together contribute to the characteristics of the population(4,12). According to this view, viral populations, rather than individual variants, are the target of evolutionary selection(4,12). Here we test this hypothesis by examining the consequences of limiting genomic diversity on viral populations. We find that poliovirus carrying a high-fidelity polymerase replicates at wild-type levels but generates less genomic diversity and is unable to adapt to adverse growth conditions. In infected animals, the reduced viral diversity leads to loss of neurotropism and an attenuated pathogenic phenotype. Notably, using chemical mutagenesis to expand quasispecies diversity of the high-fidelity virus before infection restores neurotropism and pathogenesis. Analysis of viruses isolated from brain provides direct evidence for complementation between members in the quasispecies, indicating that selection indeed occurs at the population level rather than on individual variants. Our study provides direct evidence for a fundamental prediction of the quasispecies theory and establishes a link between mutation rate, population dynamics and pathogenesis.

    ReplyDelete
  6. A virus, which exists in multiple lineages that are under strong selection by host immunity, falls into this [Inter-lineage selection versus just in case] category.
    Lineages that have more variability but are also not low-fidelity survive host immunity and persist. The rapid timescale at which this happens does not change what is going on fundamentally.


    The timescale of the selective pressure on the virus is not at all rapid with respect to the replication time of the virus. Is there a significant difference between survival of the virus in response to pressure from host immunity to survival of a species from environmental forces?

    Maybe I don't understand... Do you have a problem with genomic flexibility being evolutionarily advantageous?

    ReplyDelete
  7. anonymous asks,

    Maybe I don't understand... Do you have a problem with genomic flexibility being evolutionarily advantageous?

    One could easily imagine situations where having a "flexible" genome could be advantageous—during times of extreme environmental stress, for example.

    However, most of the time this "flexible" genome will not be advantageous. No matter how useful it might be in the future, evolution cannot create a structure just because it will be helpful a million years from now. There are no crystal balls in biology.

    ReplyDelete
  8. No matter how useful it might be in the future, evolution cannot create a structure just because it will be helpful a million years from now. There are no crystal balls in biology.

    Of course. The structure isn't created to be useful a million years from now, the structure is created by accident. If it is insufficiently deleterious it can persist until such time as it (again accidentally) becomes required. Sufficiently strong positive selective pressure at that time can then fix the structure throughout the population. If this pattern of long-term weak negative pressure followed by short-term strong positive pressure is iterated, the capacity for seemingly detrimental structures as genomic flexibility or junk DNA can become ubiquitous.

    However, when a scientist makes an individual observation, it is likely to be made in one of the long-duration weak negative selective pressure intervals. The observation is going to appear to be anti-evolutionary, because we erroneously tend to assume that selective forces are approximately constant over time. If we don't question that assumption, then the existence of a structure which is obviously (but slightly) detrimental, such as an error-prone polymerase, or junk DNA, makes us cast about looking for what the "real function" of this structure is, even if it doesn't confer a fitness advantage now, but did at some time in the past, and may well again in the future.

    ReplyDelete
  9. Anonymous says,

    Of course. The structure isn't created to be useful a million years from now, the structure is created by accident. If it is insufficiently deleterious it can persist until such time as it (again accidentally) becomes required. Sufficiently strong positive selective pressure at that time can then fix the structure throughout the population. If this pattern of long-term weak negative pressure followed by short-term strong positive pressure is iterated, the capacity for seemingly detrimental structures as genomic flexibility or junk DNA can become ubiquitous.

    Excuse me? Are you saying that there will be times when all of the junk DNA is strongly selected for?

    Give me an example of how this could work.

    Did you apply the onion test to your hypothesis?

    ReplyDelete
  10. Excuse me? Are you saying that there will be times when all of the junk DNA is strongly selected for?

    No, I'm only holding out the possibility that there may be times and conditions under which having critically functional genes spaced out from each other by "junk" may have been of use.

    Here's an example:
    We know from the geological record that every 100 million years or so there is an astronomically initiated planet-wide cataclysmic event. We have no idea what traits are required to survive such an event. We do know that at the last such time, the ancestors of all life on the earth today possessed those traits, whatever they were. Many other species, not possessing those traits, don't have any viable descendants today. The decayed genetic legacy of whatever those traits were, to an unknown degree, remains in us today, long after there hasn't been any positive selective requirement for those traits. Now, when the next such astronomical event occurs, the residual function of those traits may yet again come under intense positive selection. When that happens, it's going to look to us very much like evolution had a crystal ball and saw the crisis coming and prepared appropriately in advance, even though in reality this is simply the degraded reflection of what was necessary to survive the last such occurrence.

    There are other lesser examples of events of profound selective pressure that nevertheless occur with periodicities that greatly exceed the generation time of the organisms that come under that selection. Viral infection of a new host may fit this description.

    Is "junk DNA" something that helps get through these times of crisis? I don't know. I don't think you know either. That being the case, how can you argue that the "junk" really is useless, now and forever backwards in time under all reasonably plausible selective scenarios that may have occurred?

    ReplyDelete
  11. Anonymous asks,

    Is "junk DNA" something that helps get through these times of crisis? I don't know. I don't think you know either.

    I know a few things. I know that there are millions and millions of species that survived those times of crisis even though they had very little junk DNA. I know that there's no scientific reason to suspect that junk DNA helped any species to survive. I know that much of the junk DNA in the human genome probably arose after the last mass extinction. I know that you can't rationalize the presumed beneficial effects of junk DNA by saying that it becomes useful every 100 million years.

    That being the case, how can you argue that the "junk" really is useless, now and forever backwards in time under all reasonably plausible selective scenarios that may have occurred?

    Because it makes sense and it's compatible with the data we have. Your arguments don't make sense. You are looking for a bizarre adaptationist reason to explain junk DNA when all the evidence suggests that such a reason isn't needed to account for the presence of junk DNA.

    What's the point?

    ReplyDelete
  12. You can't imagine any scenario under which "junk" DNA could possibly be beneficial? Lets imagine a hypothetical situation: cellular exposure to an environmental agent that creates a constant number of DNA lesions per cell. The "junk", by acting as a sink for damage, can protect critical genomic regions.

    The point is that you seem to be convinced that the fitness value of all "junk" DNA is zero or less under all circumstances. I find the evidence insufficiently persuasive to argue this case as vigorously as you appear to be doing. That's all. Maybe I'm misinterpreting your text in this regard.

    ReplyDelete
  13. Anonymous says,

    You can't imagine any scenario under which "junk" DNA could possibly be beneficial? Lets imagine a hypothetical situation: cellular exposure to an environmental agent that creates a constant number of DNA lesions per cell. The "junk", by acting as a sink for damage, can protect critical genomic regions.

    Okay. let's imagine such a strange hypothetical agent. Let's assume that it's able to add up the amount of DNA in a cell and adjust its mutational ability accordingly.

    We'll apply the Onion Test.

    The onion genome is about five times larger than the human genome. This hypothetical mutagen takes a quick look at the amount of DNA in the onion nucleus and figures out that it should apply 100 hits randomly over the entire genome. It's chances of hitting a gene are low.

    Then this hypothetical mutagen examines the human genome and observes that there's five times less DNA. Instead of applying the same number of hits per mole of DNA, the mutagen decides to increase the mutation rate per mole of DNA by five-fold in order to have exactly the same number of total hits (100) as it had with the onion.

    The chances of hitting a gene at still very low but they are five times greater than in onion—assuming that onions and humans have the same number of genes.

    That's quite a sophisticated hypothetical mutagen. It's able to adjust the true mutation rate (per mole of DNA) depending on the species that's being mutated.

    I agree with your hypothetical. If there were such a strange mutagen then just having more useless DNA in your genome would confer a protective benefit.

    But there is absolutely no scientific evidence that such a strange mutagen exists. Most mutations are due to copying errors during DNA replication and that rate is measured as the number of mutations per nucleotide. (A typical value is one mutation for every 10^10 nucleotides replicated.)

    Thus, whenever the onion genome is replicated, it accumulates five times more mutations than the human genome replication.

    Other mutagens behave similarly. For example, when you bombard genomes with X-rays the damage is proportional to the size of the target. There will be five times more mutations in the onion nucleus than in the human nucleus.

    The bottom line is that there is no scientific reason to suppose that excess DNA in your genome offers any protection at all against mutation. That's because there's no reason to believe that your strange hypothetical mutagen exists.

    The point is that you seem to be convinced that the fitness value of all "junk" DNA is zero or less under all circumstances. I find the evidence insufficiently persuasive to argue this case as vigorously as you appear to be doing. That's all. Maybe I'm misinterpreting your text in this regard.

    I'm still waiting for you to come up with a single bit of scientific evidence for the adaptive value of junk DNA in the face of overwhelming scientific evidence that neither the specific sequence of junk DNA, nor it's total amount are consistent with positive selection.

    ReplyDelete
  14. Oh, I don't know. How about trying to treat the polyploid disease cells in a cancer patient with cisplatin while not killing the normal ploidy cells. Guess which kinds of cells usually win this mini-evolutionary battle against chemotherapy.

    ReplyDelete