Saturday, February 18, 2012

Exam Question #3

 
Now that you've tried Exam Question #1 and Exam Question #2, let's see how you do with this one.
There are hardly any pseudogenes in bacterial genomes. Why haven’t pseudogenes been eliminated from our genome?


16 comments :

  1. Bacteria are very strongly selected for what I might call biochemical efficiency -- the ability to duplicate DNA and reproduce very quickly and to reproduce even when resources are very limited. Therefore, having less DNA to produce and duplicate could be a strong selective advantage for bacteria.

    In humans, the strongest selection pressures involve other things. A little extra DNA hardly matters -- and although the total of pseudogenes and other DNA sequences without obvious utility is a high percentage of our genome, each individual pseudogene is too small to be selected against.

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  2. What Barbara said, plus,

    1) Humans reproduce sexually and have a slow reproductive cycle; the human genome will carry up to 2 alleles of the same gene; there's room for redundancy so any extra "baggage" won't be felt.
    2) Bacteria have a fast reproductive cycle, so any useless DNA that has to be copied requires resources; the effects become visible over time.

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  3. 'Cause bacteria rule the world?

    Interesting stuff at following link and comments, including this snippet:

    haploid genomes would be more susceptible to dominant-negative effects that pseudogenes might impart

    http://phylogenomics.blogspot.com/2010/08/lack-of-neutrality-in-bacteria-and.html

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  4. Pseudogenes haven't been eliminated from our genome because they were designed to have a function. Modern research is making this increasingly evident. See the following article for example:

    http://rnajournal.cshlp.org/content/early/2011/03/11/rna.2658311.abstract

    As new functions continue to be discovered for so-called "junk DNA," it will be harder and harder for critics to dismiss Intelligent Design.

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    1. WHile I was just going to say that you are an idiot, I add that it is quite wasteful to use pseudogenes for regulation, and that it would be quite difficult for you to show that the pseudogenes were there for regulation to begin with, rather than the system adapted to the presence of spurious and useless transcripts thus entering into a vicious circle. The pseudogenes thus become parasites of the system and get even harder to eliminate.

      Yet, if all the DNA had a function the ID bullshit would still be bullshit. No way around.

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  5. If my dissertation hadn't drained me of all ambition to write at length, I'd have given you an answer hoping for full marks. As it is, I'll leave it at there being no major selective pressure in the human genome to encourage the rapid removal of pseudogenes, which is true for most eukaryotes, whose mitochondria (in theory) allows an eukaryote to have 200'000 times as much DNA as the average prokaryote.

    On a side note, I think I would have liked your course! The questions you have shown us are both complex and subtle, making you think. Which I think is the best way to learn.

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    1. I'll leave it at there being no major selective pressure in the human genome to encourage the rapid removal of pseudogenes, which is true for most eukaryotes

      That's not an answer, though. As it is, it is a very elaborate rephrasing of the question. The answer necessarily involves explaining why there is no selective pressure to eliminate making so much extra DNA.

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    2. I don't think so. The question is why the DNA has not been eliminated, the student has to show knowledge of the concept of selective pressure as part of the answer, which I take from previous questions in Larry's blog, to be just part of what he expects from the students. I would think that you still would have to think, given data and concepts of evolution, why there would be no selection pressure against this DNA ...

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  6. I don't think there's really an answer to this out there. The most common thing I've heard is that bacteria are just under so much pressure to get things done right and quickly that they can't afford to 'waste' time and resources mucking about with junk. I've heard this applied to our mitochondrial DNA also, that the mitochondrial environment is too destructive, requiring them to quickly and constantly replicate their DNA, so they've 'selected out' junk.

    But I don't know how well supported that supposition is, it's an adaptationist argument that seems to be presented as a 'just so' story. I mean, cancerous cells can grow and they don't loose junk over time. Different closely related species of Onion (as we saw in the "onion test") have massively varying amounts of junk, but I've never heard that the 'less junky' ones are under less pressure.
    It seems to be a bit of a mystery, that bacteria have little to no junk, but prokaryotes have wildly varying amounts of junk. IF there's some functional difference, then perhaps the place to investigate is in the replication machinery and genome organizational differences between these groups (maybe having nuclear DNA and Chromosomes /allows/ for junk, but doesn't guarantee it).

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  7. They have not had enough of a negative effect on reproduction.

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  8. "As new functions continue to be discovered for so-called "junk DNA," it will be harder and harder for critics to dismiss Intelligent Design."

    The function or non-function for "junk DNA" is actually neutral with respect to evolutionary theory. When "junk DNA" was first discovered, it was a big surprise for scientists, and they advanced and evolutionary explanation for why it might exist. If all the genome is indeed functional, this poses no problem for evolution at all.

    The ID crowd have set up an absurd false dichotomy as follows: i. "evolutionists" predicted that there would be junk DNA with no function (a completely false statement). ii. If "junk DNA" is shown to have any function at all, then "evolutionists" are wrong, and the entire theory of evolution falls apart. iii. The ID people set up in opposition to the "evolutionist" viewpoint, with the false dichotomy that if the "evolutionists" were wrong the ID people have to be right.

    How, exactly, would function for "junk DNA" actually support the notion of ID (apart from the notion that it supposedly disproves the "evolutionists"?)

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  9. Physical packing constraints. Not enough space in small bacterial cells to tolerate large numbers of non-functional genes or large intergenic spaces. Would be even more true for most viruses, hence some viruses even overlap their genes. Actually doubt this simplistic explanation is correct, but nevertheless may have some truth to it in some cases. Note that one of the largest bacteria Epulopiscium (several orders of magnitude larger than E. coli) is thought to have an average sized bacterial genome (perhaps in the range of 3-6 Mb or so) but also displays extreme polyploidy and carries as estimated tens of thousands of copies of its chromosome in each cell (as compared to E. coli which will only possess 1-2 copies per cell). Wouldn't be surprised if this isn't the correct answer to the question...but thought I would throw the idea out there anyway.

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  10. Effective population size. Small enough in euks (especially multicellular ones) to tolerate an accumulation of dead genes and other crap. Prokaryotes also appear to have a strong deletion bias intrinsically, as one can see in bacteria that have become endosymbionts and gotten much smaller. (eukaryotes that experience drastic reduction in eff pop sizes tend to bloat their genomes full of crap). One would think that eukaryotes need streamlining just as much as prokaryotes, but their populations are too small for selection to "make a decision" before drift randomly fixes things.

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  11. In addition the population size differential that several people note above (leading to longer retention times and higher fixation rates for mildly deleterious stuff), it is worth adding that there are more reasons than simply efficiency for why pseudogenes might be slightly deleterious in the first place, and that population size alone does not explain all observed phenomena, as our mitochondrial genomes do not bear pseudogenes.

    Lynch argues there is a mutation risk from insertions that combines with population size to create a as composite variable Neu (effective N x mutation rate). Below a certain threshold for Neu, insertions such as gene duplications and introns are generally effectively neutral as there is low risk of them mutating into something harmful before going to fixation. As population size increases or mutation rates for genomes or genomic regions increase, such insertions become increasingly deleterious, as they may result in spurious promoters amongst other genetic elements that will mess with normal cell functioning. This explanation is consistent with the observations of plant versus animal mitochondria, where there is a vast mutation rate difference. Whereas plant and animals have overlapping nuclear mutation rates and population sizes, resulting in similar nuclear genomic architecture, there is a 100x mutation rate difference (lower in plants). The resulting lower risk of subsequent mutation appears likely to have contributed to the bloating of plant mitochondria with all manner of junk such as introns, whereas animal mitochondria appear tightly constrained and entirely lack introns. Effective population size alone cannot explain this difference.

    Hence, pseudogenes in the human nuclear genome appear to be retained on account of sufficiently low mutational risk from a combination of both a typically small mammalian population size and nuclear mutation rate.

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