Friday, 17 February 2012

The GULO Pseudogene and Its Implications for Common Descent

L-gulonolactone oxidase (GULO), the final enzyme in the biosynthetic pathway of ascorbic acid (vitamin C), is a subject that comes up often in discussions of common ancestry. The functioning GULO gene allows most plants and many animals to produce vitamin C from glucose or galactose. In some taxa, however, the GULO gene does not function in this capacity and is given the "pseudogene" label. The GULO gene is thought to be broken in humans (Nishikimi and Yagi, 1991), primates and guinea pigs (Nishikimi et al., 1994; Nishikimi et al., 1988), as well as in bats of the genus Pteropus (Cui et al., 2011).

When scientists compared the human GULO pseudogene to its functional counterpart in the rat genome, they found that regions equivalent to exons I to VI, as well as exon XI, were absent (Inai et al., 2003). This means that the human GULO pseudogene has only five exons out of the twelve found in the functional rat GULO gene. Other features of note associated with the human GULO pseudogene included one single nucleotide insertion, two single nucleotide deletions, and one triple nucleotide deletion. Researchers also identified additional stop codons. Similar mutations have been identified in the genome of chimpanzees, orangutans and macaques (Ohta and Nishikimi, 1999).

GULO and Common Descent

The GULO pseudogene -- particularly the identical base deletion in exon X at position 97 -- has long been used as an argument for establishing the validity of common descent.

Since 2003, ID proponents have been citing the claim of Inai et al. that parallel substitutious have occurred in the human and guinea-pig lineages. Inai et al. calculated the probability of attaining identical substitutions in those two lineages at the number of sites observed to be 1.83 x 10^-12, hypothesizing the phenomenon of mutational hotspots to account for this occurrence. This claim, however, is no longer tenable. As I mentioned, researchers used the rat sequence as a norm to compare the primate and guinea-pig sequence. It is more likely though that the rat GULO gene has mutated such that it is not representative of the ancestral sequence, rather than the convergence of the primate and guinea-pig sequence. This becomes clear when we consider a broader range of taxa (see here and here).

Inconsistent Use of Statistics

It is interesting to note that the argument for common ancestry based on common mutations affecting a segment of DNA is based on a form of reasoning that is uncannily similar to the specified-complexity criterion employed by advocates of design. Given the premise that mutations occur essentially at random, the inference to common ancestry is preferred over the chance hypothesis. Notice that the inference is justified not solely on the basis of high improbability (attaining the same specific mutations in multiple lineages is no more improbable than any other combination of mutations of the same number).

If the specific mutational combination occurred only once, however -- that is, before the divergence of the two lineages -- one no longer needs to explain how the same specific improbable combination of mutations occurred more than once. In this case, if we assume that there is no function for the pseudogene, as well as other assumptions (e.g. no hotspot mutations), then the common ancestry hypothesis seems preferable. If the event cannot be accounted for by common ancestry, then something fundamentally non-random must account for the phenomenon (this is what led Inai to postulate the existence of genomic hotspots where certain kinds of mutations occur with greater frequency). If Darwinists are happy to employ this kind of reasoning in their own defence of evolutionary theory, why do they object so vehemently to its use by advocates of ID?

After I had raised concerns about the prohibitive improbabilities facing the occurrence of many of the macromolecular functionally interdependent systems found in living systems, the renowned evolutionary biologist and philosopher Massimo Pigliucci wrote to me on an Internet forum,

"No evolutionary biologist I know...actually attaches probabilities to specific evolutionary events of the type you are talking about. There is no way to do that. Similarly, there is no way to attach probabilities to the set of physical laws regulating our universe, for the simple reason that we have no sample population to draw from (which is why typically you estimate probabilities)."
It was a bizarre statement, given the extent to which arguments for common descent depend on probabilistic considerations. Darwinists are quite happy to use probabilistic reasoning when it supports their case, but when a critic wants to use similar reasoning to show the limitations of the Darwinian mechanism, suddenly probabilities become incalculable and irrelevant.

What's more, as Jonathan Wells observes in the appendix of The Myth of Junk DNA, the GULO pseudogene argument is circular. Balakirev and Ayala (2003) and Khachane and Harrison (2009) take pseudogene similarities as evidence of function. When such similarities are explicable by reference to common descent, then it is taken as evidence for common descent. When such similarities are not explicable by common descent, on the other hand, it is taken as evidence of function. Moreover, there are many well documented cases of deep molecular convergence (for a catalogue, see Fazale Rana's contribution -- chapter 21 -- to The Nature of Nature). Again, when these instances are explicable by common descent, it is taken as evidence of shared ancestry. When these instances are not explicable by common descent, it is evidence of convergent evolution -- and thus the efficacy of the neo-Darwinian mechanism. This is classic circular reasoning.

Signs of Function?

There is actually some evidence to suggest that concentrations of ascorbic acid in the human fetus and in the neonate is not wholly explicable by the mother's intake of vitamin C in her diet. For example, a study conducted by Andersson et al. (1956) documented, over a period of five years, no more than two reports of infantile scurvy in malnourished South African Bantu infants. It was found that ascorbic acid plasma concentrations were comparable among infants who had been well nourished.

A further study, by Adlard et al. (1974), found substantially heightened vitamin C concentrations in the fetal human brain as compared to that of the adult. This concentration was found to fall with increased gestational age.

Salmenpera (1984) examined the levels of plasma vitamin C in infants who had been breast-fed as compared with controls who had been supplemented with vitamin C. They reported that the concentration of plasma vitamin C was the same or higher in the former compared to the latter. In fact, the concentration was roughly double the maternal concentration. The author reported, "Surprisingly, the infantile plasma concentration, which was already high compared with maternal concentration, continued to rise despite the decreasing concentration in milk ... the significance of this phenomenon is unknown."

Some researchers have actually suggested that the loss of a functional GULO may have provided a selective advantage for early man. For example, Calabrese (1982) wrote,

"Considerable controversy exists over the role of ascorbic acid in maintaining health and resisting a wide variety of diseases including cancer. It has been contended that the evolutionary loss of ascorbic acid synthesis capability in man has enhanced the occurrence of numerous chronic diseases and was essentially a maladaptive alteration which initially was well tolerated because early man lived in a habitat which supplied foods with amounts of vitamin C equivalent to what they normally may have synthesized. However, as humans migrated into habitats with less availability of vitamin C, the adverse aspects of the loss of ascorbic acid synthesizing capability came to be demonstrated (1,2). In contrast, this paper proposes that the loss of an ability to synthesize ascorbic acid in humans, far from being a neutral or totally negative mutation, may have been a critical preadaptation which markedly enhanced the survival of earlv man with a G-6-PD deficiency living in a malarial infested environment" [emphasis added]
What survival advantage might this have imparted? The paper explains,
"It is proposed that the loss of ability by humans to synthesize ascorbic aicd may have markedly enhanced the survival opportunities of early man living in a malarial infested environment. This hypothesis is based on biomedical evidence which indicates that glucose-6-phosphate dehydrogenase (G-6-PD) deficient individuals display enhanced sensitivity to ascorbic acid induced hemolysis which has been fatal at sufficiently hiqh doses and that the G-6-PD deficient trait has been selected for in malarial environments."
The highly toxic hydrogen peroxide is also known to be a biproduct of ascorbic acid biosynthesis (Banhegyi et al., 1997). Perhaps it is possible that vitamin C is produced endogenously -- and is, in fact, vital -- in utero, but that there are good biochemical reasons for supressing the expression of GULO later on -- when, in most cases, an adequate dietary intake of vitamin C has been reached.

Summary and Conclusion

The GULO pseudogene may or may not turn out to harbour some sort of function. With more and more papers coming out documenting a myriad of functions associated with pseudogenes, such a future finding should not come as a surprise. The hypothesis of limited common descent seems to me, for the time being, a reasonable one. Perhaps it is the case that all taxa belonging to the Primate Order are related by descent. Extending this inference to universal common descent, however, runs into substantial scientific problems. Whichever scenario turns out to be correct, it has no bearing on the question of the respective scientific merits of neo-Darwinism and intelligent design to account for the complexity of life.

This article was previously published on Evolution News & Views.

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