Wednesday, February 28, 2007

Human GULOP Pseudogene

Locus GULOP in the human genome is the site of a pseudogene called GULOP. In most mammals this is an active gene encoding the enzyme L-glucono-γ-lactone oxidase. This is the enzyme that catalyzes the last step in the synthesis of ascorbic acid (vitamin C). The gene is defective in humans and other primates so we can't make ascorbic acid and that causes scurvy if we don't get enough ascorbic acid in our food (Scurvy and Vitamin C).

The GenBank entry for this pseudogene is GeneID=2989. GULOP is located on chromosome 8 at p21.1 in a region that is rich in genes (map).

The human pseudogene was first identified by Nishikimi and Yagi (1991) using the intact rat gene (GeneID=60671) as a probe. They cloned and sequenced four exons that contained several deletions and several in-frame stop codons. This allowed them to conclude that the human pseudogene could not make a functional product. Several of these same mutations are found in chimpanzees, orangutans and macaques indicating that the inactive GULOP gene in all primates descends from a common ancestor that also had an inactive gene (Ohta and Nishkimi 1999).

Subsequent analysis on the GULOP locus in the human genome reveals that the pseudogene is missing most of the 5' exons that are present in the intact rat gene. In particular, exons I to VI are completely absent in the human genome. It is not known whether this deletion is responsible for the original inactivation of the GULOP gene in the primitive ancestral primate (Nishikimi et al. 1994; Ohta and Nishikimi 2003).

The human locus is also missing exon XI. In this case the deletion is probably due to recombination between Alu sequences that flank the site of the deletion. This deletion probably took place after the original inactivation event.

Inai, Y., Ohta. Y., and Nishikimi, M. (2003) The whole structure of the human nonfunctional L-gulono-gamma-lactone oxidase gene--the gene responsible for scurvy--and the evolution of repetitive sequences thereon. J Nutr Sci Vitaminol (Tokyo) 49:315-319.
Nishikimi, M. and Yagi, K. (1991) Molecular basis for the deficiency in humans of gulonolactone oxidase, a key enzyme for ascorbic acid biosynthesis. Am. J. Clin. Nutr. 54(6 Suppl):1203S-1208S.
Nishikimi, M., Fukuyama, R., Minoshima, S., Shimizu, N. and Yagi. K. (1994) Cloning and chromosomal mapping of the human nonfunctional gene for L-gulono-gamma-lactone oxidase, the enzyme for L-ascorbic acid biosynthesis missing in man. J. Biol. Chem. 269:13685-13688.
Ohta, Y. and Nishikimi, M. (1999) Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis. Biochim. Biophys. Acta. 1472:408-411.

21 comments:

  1. This is the place for all intelligent design creationists to jump in and explain the GULOP pseudogene.

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  2. Jesus put all the pseudogenes and endogenous retroviruses there to test our faith. Thanks for the post Larry.

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  3. Well obviously, it appealed to God's (oops sorry, the Intelligent Designer’s) sense of whimsy. Like er…‘vestigial’ automobile running boards.

    Anyway, as Dembski himself has said: “ ID is not a mechanistic theory, and it’s not ID’s task to match your pathetic level of detail in telling mechanistic stories. If ID is correct and an intelligence is responsible and indispensable for certain structures, then it makes no sense to try to ape your method of connecting the dots.”

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  4. Well, you see, ID is science, but not that kind of science. You know, the kind where you actually try to find out how stuff works, and so forth. I mean, you Darwinists are so unreasonable!

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  5. Oh, that's easy: the GULOP gene suffers from deterioration caused by the Fall. Adam and Eve could synthesize their own vitamin C. The reason other primates show the same disabling mutations is....is....um......is.. Do you know that abiogenesis is as unlikely as a tornado in a junkyard assembling a 747? Ergo, God created it all in 4004 BC, QED. Repent now.

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  6. Not to worry,It has been found that the components in fresh olive leaves when ingested actually provide the last "trigger",enabling ascorbic acid synthesis in humans.I am up to 30 leaves throughout the day with good results.Sincerely,Van

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  7. Journal of Creation 21(December 2007)118–127
    Why the shared mutations in the Hominidae exon X GULO pseudogene are not evidence for common descent
    by
    Royal Truman and Peter Borger

    Not available online, it seems

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  8. "This is the place for all intelligent design creationists to jump in and explain the GULOP pseudogene."

    I invited Dr Peter Borger today
    In fact , he already did react on
    a Ian musgrave article in Panda's thumb
    and
    He is still writing about all his "victorious adventures " and debating skills ( in dutch )on his own blog ...

    Tsjok 45

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  9. On what chimpanzee chromosome does the GULOP pseudogene appear?

    Do you have any predictions as to what would happen if we figured out a way to fix the pseudogene?

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  10. If the GULOP gene was “functional” in humans the additional vitamin C could lead to a suboptimal copper metabolism that could contribute to birth defects and poor brain development.

    You may be interested to know that in the world of software development there is something that is analogous to a pseudogene. It’s called an interface class. Unlike regular classes, interface classes don’t get instantiated [transcribed] into objects, yet they still serve a purpose. I don’t think it’s a good idea to assume that all pseudogenes are broken. Some may be by design.

    Suppose there was a vaccine that could "fix" your GULOP gene. Would you risk it?

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  11. Intelligent (?) Designer says,

    If the GULOP gene was “functional” in humans the additional vitamin C could lead to a suboptimal copper metabolism that could contribute to birth defects and poor brain development.

    That's crazy. People have been megadosing with vitamin C for decades and there are no such side effects. Do you really think that every woman who takes vitamin C supplements is putting her children at risk?

    Where in the word do you guys come up with these ideas?

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  12. I followed your link.

    It's difficult to sort out fact from rumor on most of the websites. When you start looking for real scientific evidence there's little to be found.

    What it boils down to is this: two studies on humans suggest that megadoses of vitamin C may lower the activity of copper binding protein but there's no evidence of detrimental effect due to copper deficiency.

    I couldn't find a single scientific study showing that megadose levels of vitamin C causes "birth defects and poor brain development" as you claim.

    If they exist, you should have no trouble providing me with the references.

    waiting .....

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  13. Interested readers can google “copper deficiency” “birth defects” or “copper deficiency” “brain development”. But I am not trying to prove that mega doses of vitamin C cause birth defects. I am only suggesting that it’s a bad idea to assume that pseudogenes are broken. You may be right about the GULOP.

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  14. This year, scientists showed that man has an additional 678 unique genes relative to chimp and other primates. In contrast, man and chimp have only a few shared indel mutations as they are found in the GULO gene. These errors may be explained using the common descent (CD) hypothesis, but the 678 novel genes in man are merely a falsifying observation of CD. This fact can be taken as evidence that man and chimp did not have a common ancestor, and we only have to explain the observation of shared errors in GULO and a few other genes. This only requires a new interpretational framework. We did that: non random interspecies "hotspot" mutations. Unlikely? Well, not as unlikely as the "evolution" of 678 novel genes. The interspecies hotspots for indel mutations give an illusion of common descent. That's a rule of GUToB.

    Darwin's trick was to postulate "common descent PLUS modification", a proposition that CANNOT be falsified. If a trait cannot be explained by common descent, it is modification, and if it is not modification it is common descent.

    So, Darwinism "explains" every observation we did in the past, we do in the present and we will do in the future. Therefore it is pseudoscience.

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  15. peter borger says,

    This year, scientists showed that man has an additional 678 unique genes relative to chimp and other primates.

    Not they did not. Whoever told you that is lying. They are not unique genes, they are duplicate genes.

    You are referring to work from Mathew Han's lab at Indiana University. His lab studies the evolution of gene families in mammals. What they do is look at a set of about 9,000 gene families to see if the number of genes in each family expands or contracts in different lineages.

    The members of a gene family are often exact duplicates of each other and in most cases the gain or loss of one or two copies has no effect on the phenotype of the species. The studies are attempting to develop a robust hypothesis for gene family evolution. The leading contender is something known as the Birth-and_Death Hypothesis [see Mammalian Gene Families: Humans and Chimps Differ by 6%, Birth-and-Death Evolution in Mammalian Gene Families, The Evolution of Gene Families].

    Hahn and his coworkers have found that among all 9,000+ gene families, the human lineage has gained 678 new members by gene duplication and the chimpanzee line has lost 740 members by deletion/recombination since humans and chimps diverged. Thus, the human genome has a total of 1418 genes not found in the chimp genome.

    Most (all?) of these differences are thought to have no, or very little, effect on the appearance of chimps and humans but the authors argue that some of them may be responsible for the differences in appearance. Their main point is that we should not attribute all the differences to changes in the regulation of gene expression.

    ... the 678 novel genes in man are merely a falsifying observation of CD [common descent]. This fact can be taken as evidence that man and chimp did not have a common ancestor ....

    Nonsense. The fact that the human lineage has gained 678 additional family members by gene duplication while the chimp lineage has lost 749 family members is perfectly consistent with common descent.

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  16. by the old --now outdated --definition these genes may be "duplicates" but they are unique in the sense that they are in a new genomic context. Besides, it is merely assumed they have originated in duplication events. A duplicate is redundant by definition and will decay rapidly. The fact they are in the genomes as duplicates would merely argue for 1) recent origin 2) stringent functional contraint. For redundancies 2) is paradoxical, therefore I prefer 1). Ohno predicted a 1:10 ratio (it was more a wild guess) for novel-function-acquiring "duplicates", but apparently now every duplication is functional and acquires novel functions?

    The 2005 human-chimp comparison showed 36 unique protein coding sequences in human. The miRNA gene analyses between chimp and man showed 10 percent unique miRNA genes in man. The gap is getting wider. And the gap is not only quantitative.

    Anyway, the blog topic is on GULO and the indel in exon X is a hotspot in all other species Truman and I studied and reported in the science literature.

    Such interspecies hotspots also occurred in the UOX pseudogenes (see: Oda et al, J Mol Evol 2002). I think, non-random mutations that line up to induce an illusion of common descent are much more common than acknowledged by the evolutionary community, but they explain an alignment of shared errors independent of common descent.

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  17. By the way, the reference that Heleen provided can now be read online:

    Why the shared mutations in the Hominidae exon X GULO pseudogene are not evidence for common descent
    Paper by Royal Truman and Peter Borger

    http://uk.creation.com/images/pdfs/tj/j21_3/j21_3_118-127.pdf

    I'd be interested in reading Larry's thoughts.

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  18. I need help assessing the evidence from comparing the GULO gene (1) between rat and human, (2) between chimp and human. RE: (1): what is the effect if any of the large deletion in the human GULO pseudogene on the assessment of the comparison and the conclusion of common ancestry; RE (2): do chimps and humans share this deletion.

    Jitse van der Meer

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  19. In this case the deletion is probably due to recombination between Alu sequences that flank the site of the deletion. This deletion probably took place after the original inactivation event.
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    ReplyDelete
  20. Evolution by natural selection equals common descent plus modification [E(NS) = CD + M] an it is a non-falsifiable concept.

    Shared traits between organism prove common descent, whereas unique traits proof modifications. That holds for the DNA, for morphology, for ontology, for all observations. Therefore, it does not belong to the realm of science.

    ReplyDelete