This is the second post discussing creationist1 papers on pseudogenes. The first post addressed a paper by Jeffrey Tomkins on the β-globin pseudogene [Creationists questioning pseudogenes: the beta-globin pseudogene]. This post covers another paper by Tomkins claiming that the GULO pseudogenes in various primate species are not derived from a common ancestor but instead have been deactivated independently in each lineage.
The Tomkins' article was published in 2014 in Answers Research Journal, a publication that describes itself like this:
ARJ is a professional, peer-reviewed technical journal for the publication of interdisciplinary scientific and other relevant research from the perspective of the recent Creation and the global Flood within a biblical framework.Tomkins explains two fundamental axioms of Young Earth Creationism.
- "An emerging theme from the continuing progression of genomics research across the spectrum of eukaryotic life is the widespread decay of pathways for vitamin-synthesis (Helliwell, Wheeler, and Smith 2013). This paradigm is of great importance to the creationist model of genetic entropy which postulates that genomes are in a continual state of degradation over time, not forward progressing evolution (Sanford 2010)."
- "Another important component of the creationist model of origins is the idea of molecular discontinuity between unrelated taxon (Tomkins and Bergman 2013). As will be demonstrated in this report, the enigma of the GULO pseudogene analyzed in the light of new genomic evidence most closely aligns with a creationist model incorporating both of these paradigms."
As you might have guessed, Tomkins argues that that the pattern is inconsistent with common ancestry and lends support to Young Earth Creationism. Here's the article ...
The GULO gene encodes the enzyme L-glucono-γ-lactone oxidase, the terminal enzyme in the synthesis of ascorbic acid. Ascorbic acid is required in the synthesis of collagen and a few other processes in mammals. Mutations in the GULO gene can lead to loss of function but this is not lethal in many species because they get enough ascorbic acid in their diet.The Human GULO Pseudogene—Evidence for Evolutionary Discontinuity and Genetic Entropy
Jeffrey P. Tomkins, Institute for Creation research, Dallas, TX, USA
Answers in Genesis
Abstract: Modern genomics provides the ability to screen the DNA of a wide variety of organisms to scrutinize broken metabolic pathways. This wealth of data has revealed wide-spread genetic entropy in human and other genomes. Loss of the vitamin C pathway due to deletions in the GULO (L-gulonolactone oxidase) gene has been detected in humans, apes, guinea pigs, bats, mice, rats, pigs, and passerine birds. Contrary to the popularized claims of some evolutionists and neo-creationists, patterns of GULO degradation are taxonomically restricted and fail to support macroevolution. Current research and data reported here show that multiple GULO exon losses in human, chimpanzee, and gorilla occurred independently in each taxon and are associated with regions containing a wide variety of transposable element fragments. Thus, they are another example of sequence deletions occurring via unequal recombination associated with transposable element repeats. The 28,800 base human GULO region is only 84% and 87% identical compared to chimpanzee and gorilla, respectively. The 13,000 bases preceding the human GULO gene, which corresponds to the putative area of loss for at least two major exons, is only 68% and 73% identical to chimpanzee and gorilla, respectively. These DNA similarities are inconsistent with predictions of the common ancestry paradigm. Further, gorilla is considerably more similar to human in this region than chimpanzee—negating the inferred order of phylogeny. Taxonomically restricted gene degradation events are emerging as a common theme associated with genetic entropy and systematic discontinuity, not macroevolution.
The human gene is nonfunctional giving rise to a unitary pseudogene located on chromosome 8 at p21. As a result, ascorbic acid is now an essential component of the human diet. Because it has become essential, it is now called a vitamin (vitamin C) (see Helliwell et al., 2013) [Human GULOP Pseudogene].
The standard explanation for the origin of this pseudogene—and all other unitary pseudogenes—is that the original gene became inactivated by mutation at some time in the past. That null allele then became fixed in the population by random genetic drift. All descendants of that population inherited the pseudogene.
Tomkins takes a scattergun approach to the problem by bringing up all kinds of objections to the standard explanation. I don't have time to discuss all of his objections and I don't have enough knowledge of some of the issues to respond to his points. For example, I don't know enough about bird evolution to say whether the pattern of GULO gene loss is compatible with common ancestry or not.
Let's just look at the pseudogenes in primates to see which explanation is more reasonable. Lapachapelle and Drouin (2011) looked at the pattern of neutral substitutions in the primate lineages. All Haplorrhini3 primates (e.g. humans, chimpanzees, macaque, gibbon etc) have a pseudogene with certain shared characteristics, including a number of identical substitutions. This suggests that the ancestor of all Haplorrhini primates contained the pseudogene, which must have arisen shortly after the the split between Haplorrhini and Strepsirrhini (lemurs, galagos, etc.). According to the fossil record, the split occurred about 63 million years ago.
Lapachapelle and Drouin calculated that the pseudogene must have arisen about 61 Mya based on the neutral substitution rate. The fact that these values are so close lends support to the idea that all Haplorrhini species are derived from a common ancestor that lost the GULO gene.
The authors also looked at specific deletions to see if the results are consistent with common ancestry. All of the primate pseudogenes are missing exons 1 and 2 of the intact, functional, gene.4 They compared the sequences of the human, chimpanzee, and macaque genes to that of the galago gene. The result is shown in Figure 4 of their paper (see below).
Note that the large deletion of the two exons ("deletion") occurs at the same position in the human, chimpanzee, and macaque genomes. All three genomes also have two identical seven base pair indels in the upstream region preceding exon 1. This is evidence of common ancestry.
Lachapelle and Drouin were testing the hypothesis that large deletions in the GULO pseudogene were due to aberrant recombination between flanking transposable elements (TE). They mapped all surrounding transposons in the primate genes and concluded that TE's did not play a role in the deletion.
Tomkins discusses this paper in his creationist journal article. He ignores the evidence of common descent and focuses instead on the transposable elements. He points out that Lachapelle and Drouin failed to find evidence that TE's were responsible for the deletions. Here's what he wants his readers to conclude from a paper that strongly supports common descent ....
Despite the fact that TEs are apparently one of the main genomic drivers of deletion events in the genome, the researchers (Lachapelle and Drouin 2011) concluded that the lineage specific TE insertion patterns, which defied the standard inferred evolutionary model for primates, did not contribute to the loss of exons in the GULO gene. Thus, their evolutionary presuppositions caused the rejection of otherwise strong genomic data that implicated TE related unequal recombination at the GULO locus (resulting in exon deletion) that occurred in taxonomically restricted events.I think it's disingenuous of Tomkins to focus on that aspect of the study while ignoring all the evidence for common descent.
The GULO pseudogene locus on human chromosome 8 is in a gene-rich region. Orthologous genes are present at the same site in all vertebrate species although the order of the surrounding genes has been repeatedly shuffled by microrearrangements (Yang, 2013).
The presence and order of the exons within the GULO gene/pseudogene in diverse vertebrates is consistent with several independent inactivations and descent from a common ancestor (Yang, 2013). One of them occurred in the primate lineage. All of the primate pseudogenes are missing exons 1 & 2 as well as exons 5, 7, and 10 as shown in the figure below.
The data is consistent with an ancestral pseudogene gene that was missing exons 1, 2, 5, 7, and 10. Exons 3 & 4 were subsequently lost in a separate events in the gibbon lineage. The orangutan and human pseudogenes are similar with respect to exon loss and the chimpanzee pseudogene is probably the same. (The 5′ region of the GULO pseudogene was not present in the chimp genome sequence.)
Tomkins doesn't discuss the evidence for the common ancestry of the primate pseudogenes and he doesn't try to explain the pattern according to a Young Earth Creationist worldview. Instead, he draws attention to another part of Yang's paper—the part where he documents the rearrangements of the genes surrounding the GULO locus. There's nothing unusual about such rearrangements. They are common between closely related species and even within a species. Over time, blocks of genes are shuffled and re-ordered so that distantly related vertebrates show very little synteny.
Tomkins thinks this is a serious problem for evolution ...
The GULO gene lies within a gene-dense region in all vertebrate genomes studied thus far (Yang 2013). Related to this fact is the evolutionary anomaly that the gene neighborhood surrounding the GULO locus is rearranged across the vertebrate spectrum of life, and the patterns cannot be readily resolved into the standard inferred evolutionary lineages (Yang 2013).Once again, Tomkins is cherry-picking the data to focus on minor anomalies that don't fit with his strawman version of evolution. Once, again, he ignores the much more important data in the same paper that supports an ancient origin of an ancesral GULO pseudogene.
Let me close by mentioning one other "anomaly" that Tomkins raises. He questions whether the functional rat gene is an appropriate standard of comparison. You might be amused by his logic ...
Traditionally, the human GULO pseudogene has been compared to the functional rat GULO gene (Nishikimi, Kawai, and Yagi 1992; Nishikimi et al. 1994; Ohta and Nishikimi 1999). According to the UCSC genome browser (genome.ucsc.edu) and the Rat Genome Database (rgd.mcw.edu), the rat GULO gene (chr15, region p12) is oriented and transcribed on the minus strand. Interestingly, the human and ape GULO pseudogenes are oriented in the plus strand configuration (chr8, region p21.2 in human). While the rat GULO gene may serve as a general guide to exon presence and absence in degraded GULO genes in other mammals, the rat GULO is clearly in a different chromosomal configuration (compared to humans and apes) and represents a unique design pattern specific to rodents (mouse GULO is on chr15, minus strand).
1. In this case, Young Earth Creationist.
2. For more information on the GULO pseudogene see ...
How do Intelligent Design Creationists deal with pseudogenes and false claims?
Junk & Jonathan: Part 8—Chapter 5
Human GULOP Pseudogene
3. Also spelled Haplorhini.
4. Lachapelle and Drouin include a short 5′ exon (#1) that isn't present in most species. It's likely an artifact. I renumbered the exons according to Yang (2013).
Helliwell, K.E., Wheeler, G.L., and Smith, A.G. (2013) Widespread decay of vitamin-related pathways: coincidence or consequence? TRENDS in Genetics, 29:469-478. [doi: 10.1016/j.tig.2013.03.003]
Lachapelle, M.Y., and Drouin, G. (2011) Inactivation dates of the human and guinea pig vitamin C genes. Genetica, 139:199-207. [doi: 10.1007/s10709-010-9537-x]
Yang, H. (2013) Conserved or lost: molecular evolution of the key gene GULO in vertebrate vitamin C biosynthesis. Biochemical genetics, 51:413-425. [doi: 10.1007/s10528-013-9574-0]
