The Genomic Evidence for Common Descent: 3. Shared identical pseudogenes

If a university lecturer receives six term papers that not only share the same four paragraphs in the conclusion which are word-for word from Wikipedia, except for identical spelling errors at the same place in the paragraphs that closely resemble Wikipedia, she is unlikely to conclude that purely by chance, all six students independently wrote four concluding paragraphs that happened to resemble Wikipedia word for word, and independently made the same spelling mistakes. Rather, she is entitled to conclude that one student plagiarised Wikipedia, making a few spelling errors in the process, and that the remaining five students copied that original paper.

A similar phenomenon exists in comparative genomics, where identical genetic 'errors' are found in exactly the same place in the genome when we compare genomes from a number of related species. These 'errors' include broken genes, remnants of ancient retroviral infection, mobile genetic parasites, and markers of DNA repair. These are not design features, but evidence of an ancient accident which occurred in an ancestral species, and was subsequently inherited by descendant species. This post will review the evidence from pseudogenes.

Pseudogenes are genetic elements that resemble genes but are not able to produce the product for which that gene normally would code. Three types of pseudogene exist: unitary, duplicated and processed.

• Unitary: result when a normally functioning gene acquires a crippling mutation that prevents it from functioning. One of the better known unitary pseudogenes is the gulonolactone oxidase pseudogene, GULOP. Most organisms are able to make their own vitamin C, but in a number of species, most notably humans, apes, guinea pigs and bats, the gene which codes for L-gulonolactone oxidase, one of the enzymes involved in vitamin C biosynthesis is non-functional. 
• Duplicated: occurs when a gene is copied, and one or more of the copies becomes inactivated through mutation. The haemoglobin gene family is one notable example as there are a number of haemoglobin pseudogenes in addition to the functional haemoglobin genes, the former having arisen via duplication and inactivation. 
• Processed: these occur if the RNA transcript of a gene, which normally is used by the cell as the ‘recipe’ to create the protein for which it encodes, is copied via reverse transcriptase to a DNA copy and is inserted randomly into the genome. In order to appreciate how readily one can tell the difference between a processed pseudogene and the gene from which it originated, it is useful to know some of the details of genetics. A working gene will have a promoter element (a section of genetic material involved in initiating gene transcription), while the part of the gene that actually codes for the protein will be broken up with genetic elements called introns that are spliced out during transcription. The tail-end of the RNA copy of a gene will contain what is called a poly-A tail, which is important in stabilising the RNA copy. The processed pseudogene lacks introns and a promoter element, but has a poly-A tail added.

Common descent would predict that species descending from a common ancestor not only would have similar genes, but have most of those genes in the same order. Building on from the information above, we would also predict that if an organism was infected by a retrovirus that became fixed in its genome, had one of its genes incapacitated by mutation and converted to a pseudogene, or had a number of retrotransposition events occurring in its genome, then these ‘genetic errors’ would be inherited by species descended from the ancestral species. 

Conversely, special creation would have no credible answer other than to claim that purely by chance:

• the same retrovirus inserted into the same location,
• the same gene became incapacitated by exactly the same mutation
• the same RNA transcript of a gene became reverse transcribed and pasted into the same location
• the same retrotransposon copied and inserted itself into the same location in related species. 

The odds of this occurring by chance are remote even if we are referring only to a single event. In reality, there are multiple examples of identical shared ‘genetic errors’ in species which according to mainstream biology share a common ancestor, and the pattern of these shared errors agrees remarkably well with the accepted evolutionary family tree. Needless to say, the chances of this occurring by chance are so remote as to be negligible. The most parsimonious interpretation of this is the acquisition of these ‘genetic errors’ in ancient species whose ancestors have inherited these mistakes.

The literature is replete with examples. The first – and arguably most famous example – is that of the GULO-P pseudogene which in humans, chimpanzees, orangutans and macaques [1] is broken in exactly the same was. (For those interested in the details, the 164 nucleotide sequence of exon X shared a single nucleotide deletion). While guinea pigs also have a non-functional GULO gene, this was inactivated in a completely different way [2] and therefore represents a separate pseudogenisation event. The GULO pseudogene in humans, apes and old world monkeys is broken in exactly the same way, consistent with the incapacitation of GULO in the common ancestor of these primates.

After a gene is rendered non-functional, it becomes selectively neutral, which means that it is free to acquire random mutations. If we look at all the species that have the same pseudogene in common, those that share a recent common ancestor should differ by fewer random mutations. Conversely, those that have a distant common ancestor will have had more time to accumulate random mutations, and therefore will be less similar. By creating a family tree based on this mutation data, we should be able to create a tree roughly consistent with the expected evolutionary tree. This is exactly what we see when we look at the GULO data in primates:

Source

The primate data clusters closely together, with humans and chimpanzees closest of all. Rodents cluster closely together, with guinea pigs clustering closely with the rodents. This is exactly what we’d expect if common descent was true. Special creation simply has no credible answer. Remember, when we look at the primate data, we’re looking at random mutations in a non-functional gene. The creationist either has to assume that this occurred purely by chance; the odds of which are so remote as to be practically impossible or answer:

• Why did God create primates with a broken vitamin C synthesis system, leaving others with the ability to synthesise vitamin C
• Why did God create humans, apes and old world monkeys (which according to evolutionary biology form a clade, or group of organisms sharing a common ancestor) with a GULO pseudogene broken in exactly the same way?
• Why did God then insert random mutations into this broken pseudogene in such a way as to allow one to construct an evolutionary family tree that agrees with the conventional evolutionary tree derived from morphological data?

This is why the biochemist and intelligent design advocate Michael Behe admitted that the GULO data is powerful evidence for common descent:

When two lineages share what appears to be an arbitrary genetic accident, the case for common descent becomes compelling, just as the case for plagiarism becomes overpowering when one writer makes the same unusual misspellings of another, within a copy of the same words. That sort of evidence is seen in the genomes of humans and chimpanzees. For examples, both humans and chimps have a broken copy of a gene that in other mammals helps make vitamin C As a result, neither humans nor chimps can make their own vitamin C.  

[…] 

The same mistakes in the same gene in the same positions of both human and chimp DNA. If a common ancestor first sustained the mutational mistakes and subsequently gave rise to these two modern species, that would very readily account for both why both species have them how. It's hard to imagine how there could be stronger evidence for common ancestry of chimps and humans. (Emphasis mine) [3]

The enzyme cytochrome P450 C21 is of critical importance in the biosynthesis of steroid hormones. Humans have both a working copy of the CYP21 gene (which has eight exons), as well as a pseudogene, which is damaged in three main ways:

• An eight base pair deletion in exon 3 of the gene
• A one base pair substitution at codon 318 of exon 8
• A single nucleotide insertion in exon 7

Kawaguchi et al analysed the DNA of humans, orangutans, chimpanzees and gorillas to clarify how and when the defects in the CYP21 pseudogene occurred:

The primary purpose of this study has been to determine the evolutionary origins of the three defects characterizing the human CYP21P gene. The study shows that the 8-bp deletion in exon 3 is present in the chimpanzee but not in the gorilla or orangutan genes, whereas the T insertion in exon 7 and the substitution generating the stop codon in exon 8 are restricted to human genes. [4]

In other words, the 8 base pair deletion occurred in a common ancestor of humans and chimpanzees, while the substitution and insertion occurred after the human-chumpanzee speciation event: 

Our results are consistent with this scenario: the 8-bp deletion apparently occurred after the gorilla lineage split off but before the chimpanzee and human lineages separated from each other. We can thus date the occurrence of the 8-bp deletion rather precisely within a relatively short period of some 6 Myr ago. The deletion was followed, in the human lineage, by the two other defective mutations. [5]

Again, recall our analogy of multiple examination papers with the same wrong errors and the same mistakes in the wrong answers, down to the same spelling errors. No one would seriously advance multiple independent errors as a valid explanation. Rather, they'd conclude that copying had occurred. The same applies here. When we have identical errors in the CYP21 pseudogene of chimpanzees and humans, it stretches credibility to assume that:

• Purely by chance, chimpanzees and humans both have a CYP21 pseudogene which arose via a duplication event
• Purely by chance, they both acquired the same eight base pair deletion
• Common descent, with the duplication event occurring in a species ancestral to human and chimpanzee which was then passed down to chimpanzee and human lineages is the only credible explanation. 

Other examples of shared pseudogenes include:

1. The GBA gene, which codes for the enzyme glucocerebrosidase has a pseudogene present not only in humans, but in chimpanzees and gorillas. Human, chimpanzees and gorillas share the same 55 base pair deletion. [6]

2. The RT6 gene normally codes for a protein which is found on the surface membrane of T lymphocytes (a class of white blood cell). In both humans and chimpanzees it is a pseudogene, which means this protein is not expressed. Haag et al have examined the human and chimpanzee RT6 pseudogene:

We have now cloned and sequenced the homologues of the RT6 genes from humans of distinct ethnic backgrounds and of the chimpanzee. Surprisingly, in each case, three premature in-frame stop codons preclude expression of the single copy RT6 gene as a cell surface protein. Otherwise, the RT6 genes of human and chimpanzee exhibit high structural conservation to their rodent counterparts. RNA expression analyses indicate that the RT6 gene is not transcriptionally active in human T cells or any other human tissue analyzed so far. To our knowledge, RT6 represents the first mammalian membrane protein identified that has been lost universally in the human and chimpanzee species due to gene inactivation. [7]

Again, here is an example of humans and chimpanzees having the same pseudogene with the same crippling mutation, which makes sense if humans and chimpanzees shared a common ancestor in which this mutation took place and from whom the two lines inherited the pseudogene. From a special creationist point of view, this is inexplicable.

3. Humans and apes are unable to synthesise the enzyme urate oxidase, as the gene which normally would code for it is a pseudogene. In humans, chimpanzees, this is due to the same mutation. In gibbons, which are also unable to synthesise urate oxidase, this is due to a separate mutation event:

Two nonsense mutations at codon positions 33 and 187 and an aberrant splice site were found in the human gene. These three deleterious mutations were also identified in the chimpanzee. The nonsense mutation at codon 33 was observed in the orangutan urate oxidase gene. None of the three mutations was present in the gibbon; in contrast, a 13-bp deletion was identified that disrupted the gibbon urate oxidase reading frame. These results suggest that the loss of urate oxidase during the evolution of hominoids could be caused by two independent events after the divergence of the gibbon lineage; the nonsense mutation at codon position 33 resulted in the loss of urate oxidase activity in the human, chimpanzee, and orangutan, whereas the 13-bp deletion was responsible for the urate oxidase deficiency in the gibbon. [8]

4. Humans have thirteen genes which code for the oxygen-carrying molecule haemoglobin. Four of them in adults are functional, while five are active only in the foetal stage and are inactivated around birth. The remaining four are pseudogenes. The genes occur in two clusters, the alpha cluster (three pseudogenes and four genes) and the beta cluster (one pseudogene and five genes).

The single pseudogene in the beta cluster - the ψβ pseudogene - is considerably degraded, with around 30% of the gene sequence mutated when compared with the functional β haemoglobin gene. Given the known rate of mutation, this means the ψβ pseudogene must have been disabled a long time ago. Therefore, common descent would predict we'd see it not only in humans and the great apes, but in more distantly related primates, and that is exactly what we see. The ψβ pseudogene is seen in humans, apes, baboons and new world monkeys. Furthermore, when we examine the ψβ pseudogene in humans, chimpanzees and gorillas, we see the same crippling mutations:

These three pseudogenes each share the same substitutions in the initiator codon (ATG → GTA), a substitution in codon 15 which generates a termination signal TGG → TGA, nucleotide deletion in codon 20 and the resulting frame shift which yields many termination signals in exons 2 and 3. [9] 

One of the pseudogenes in the alpha cluster, the ψζ pseudogene is almost identical with the working ζ foetal haemoglobin gene. It is another example of a duplicated pseudogene, one which was inactivated only a relatively short time ago [10]. When we look at the genome of the chimpanzee, regarded as the closest living relative of humans, we see two ζ haemoglobin genes, confirming that the conversion of the duplicated ζ gene to a pseudogene took place after the human-chimp speciation event, relatively recently:

Beta haemoglobin gene cluster. Pseudogenes are black

Source: Fairbanks D.J. "Relics of Eden: The Powerful Evidence of Evolution in Human DNA" (2007, Prometheus Books)

This consonance between morphological and molecular phylogenetic trees is exactly what common descent would predict, and utterly impossible to honestly reconcile with common design, unless God was deliberately creating life with errors in order to fake common descent.

This barely touches the surface of the vast array of pseudogene evidence demonstrating human-ape common ancestry. As molecular biologist Daniel Fairbanks notes:

With a few notable exceptions, chimpanzees and humans have the same pseudogenes in the same places, and they are, on average, about 98 percent similar. [11]

Cell biologist and cancer researcher Graeme Finlay in a 2003 paper summarising the genomic evidence for common descent likewise echoes Fairbanks' comments:

Our genome contains 6,000 to 10,000 derelict genes or gene fragments (pseudogenes) that no longer produce functional proteins (Figure 2). Some are disabled versions of genes which remain functional in other species. Others are inactive copies or duplicated fragments of functional genes. Each pseudogene is unique. It is the product of a random, unrepeatable originating event (or series of events) that occurred during the history from which humanity arose. Pseudogenes therefore provide unambiguous evidence for the animal ancestry of humans. [12]

Needless to say, the odds of these species purely by chance having the same genes convert to pseudogenes with exactly the same genetic mutation causing the pseudogenisation of these genes is so remote as to be impossible. Common design fails to explain this evidence:

• It fails to explain why, if a creator did not intend for humans and apes to have these genes in the first place, were they created with broken versions of genes that in other animals are functional.
• It fails to explain why these broken genes were created in closely related animals with the same crippling mutation.
• It fails to explain why these broken genes were also created with random mutations places in exactly the right way to allow scientists to construct evolutionary family trees that are consonant with the standard evolutionary family trees. Such consonance is exactly what one would expect if common descent was true. Special creation is simply unable to honestly account for this evidence. 

The evidence for common descent just from pseudogenes is clear, and unarguable.

References

1. Ohta Y, Nishikimi M "Random nucleotide substitutions in primate nonfunctional gene for L-gulono-gamma-lactone oxidase, the missing enzyme in L-ascorbic acid biosynthesis.” Biochim Biophys Acta. (1999) 18;1472(1-2):408-11.

2. Nishikimi M, Kawai T, Yagi K. "Guinea pigs possess a highly mutated gene for L-gulono-gamma-lactone oxidase, the key enzyme for L-ascorbic acid biosynthesis missing in this species." J Biol Chem. (1992) 267(30):21967-72.

3. Behe M “The Edge of Evolution. The Search for the Limits of Darwinism” (2007, Free Press) pp 71-72

4. Karaguchi H, O'hUign C, Klein J "Evolutionary Origin of Mutations in the Primate Cytochrome P450c2l Gene" Am. J. Hum. Genet. (1992) 50:766-780

5. ibid, p 777.

6. Wafaei J.R., and Choi F.Y., "Glucocerebrosidase Recombinant Allele: Molecular Evolution of the Glucocerebrosidase Gene and Pseudogene in Primates" Blood Cells, Molecules, and Diseases (2005) 35: 277-85.

7. Haag F, Koch-Nolte F, Kiihl M, et al. Premature stop codons inactivate the RT6 genes of the human and chimpanzee species. J Mol Biol (1994) 243:537-546

8. Xiangwei Wu, Donna M. Muzny, Cheng Chi Lee, C. Thomas Caskey "Two independent mutational events in the loss of urate oxidase during hominoid evolution" Journal of Molecular Evolution (1992) 34:78-84

9. L.Y.Edward Chang, Jerry L. Slightom "Isolation and nucleotide sequence analysis of the β-type globin pseudogene from human, gorilla and chimpanzee" Journal of Molecular Biology (1984) 180:767:783
10.  W. C. Wong et al., "Comparison of Human and Chimpanzee Zeta 1 Globin Genes" Journal of Molecular Evolution (1985) 22: 309-15
11. Fairbanks D.J. "Relics of Eden: The Powerful Evidence of Evolution in Human DNA" (2007, Prometheus Books) p 54

12. Finlay G "Homo divinus: The Ape that Bears God's Image.” Science and Christian Belief (2003) 15:17–40.