Prediction 4.4: Molecular evidence - Redundant pseudogenes
Other molecular examples that provide evidence of common ancestry are curious DNA sequences known as pseudogenes. Pseudogenes are very closely related to functional, protein-coding genes. The similarity involves both the primary DNA sequence and often the specific chromosomal location of the genes. The functional counterparts of pseudogenes are normal genes that are transcribed into mRNA, which is in turn actively translated into functional protein. In contrast, pseudogenes have faulty regulatory sequences that prevent the gene from being transcribed into mRNA, or they have internal stop codons that keep the functional protein from being made. In this sense, pseudogenes are molecular examples of vestigial structures.
However, pseudogenes are included here under a separate prediction because many pseudogenes are unusual in an additional way. Morphological vestiges have lost their original function, and the organism carrying the vestige has likewise lost that function. In contrast, pseudogenes have lost their original function, yet the organism itself may still retain that function if it carries the functional counterpart of these pseudogenes. Pseudogenes that are vestigial in the morphological sense, like the vitamin C synthesis pseudogene, are considered in prediction 2.3. The remaining type of pseudogene, in which an organism carries both a functional gene and one or more counterpart pseudogenes, is hereafter termed a "redundant pseudogene."
Most pseudogenes are largely non-functional. There are several lines of evidence that support this conclusion. First, the presence or absence of most specific pseudogenes has no measurable effect on organismal phenotype. Second, there are good mechanistic, genetic arguments indicating pseudogenes have little, if any, function. Pseudogenes have complex sequences highly similar or identical to those required for the proper function of other enzymatic or structural proteins. These normal genes are actively transcribed and translated into proteins, whereas pseudogenes are not. Thus, pseudogenes cannot perform the functions of the proteins they encode. If pseudogenes do have a function, they must perform relatively simple functions for which the protein encoded by them was not designed. Note that some pseudogenes are the non-functional counterparts of structural or enzymatic RNAs that are never normally transcribed into protein. In fact, the first pseudogenes ever discovered were broken pseudogenes related to normal ribosomal RNA genes.
Third, simple functions do not require highly specific, complex DNA sequences. If a pseudogene has little or no function, then most mutations in the pseudogene will have no functional consequences, and the mutations will not be weeded out by purifying selection. Therefore, we expect that pseudogenes should accumulate mutations at the background rate of mutation. As expected if pseudogenes have little, if any, function, the majority of pseudogenes accumulate mutations at the fastest rate known for any region of DNA in animal genomes. Furthermore, the rate of mutation inferred for pseudogenes from phylogenetic analysis matches very closely the measured rates of spontaneous mutations. For more information and references, see Prediction 5.8.
Fourth and finally, we understand how redundant pseudogenes are created, and we have observed the creation of new redundant pseudogenes in the lab and in the wild. Redundant pseudogenes originate by gene duplication and subsequent mutation. Many observed processes are known to duplicate genes, including transposition events, chromosomal duplication, and unequal crossing over of chromosomes.
These facts offer strong support for the conclusion that most pseudogenes have little, if any, function. Like transpositions (see prediction 4.3), the creation of new redundant pseudogenes by gene duplication is a rare and random event and, of course, any duplicated DNA is inherited. Thus, finding the same pseudogene in the same chromosomal location in two species is strong evidence of common ancestry.
Confirmation:
There are very many examples of redundant pseudogenes shared between primates and humans. One is the øç-globin gene, a hemoglobin pseudogene. It is shared among the primates only, in the exact chromosomal location, with the same mutations that destroy its function as a protein-coding gene (Goodman et al. 1989). Another example is the steroid 21-hydroxylase gene. Humans have two copies of the steroid 21-hydroxylase gene, a functional one and a untranslated pseudogene. Inactivation of the functional gene leads to congenital adrenal hyperplasia (CAH, a rare and serious genetic disease), giving positive evidence that the 21-hydroxylase pseudogene lacks its proper function. Both chimpanzees and humans share the same eight base-pair deletion in this pseudogene that renders it incapable of its normal function (Kawaguchi et al. 1992).
Potential Falsification:
As explained above, observed gene duplications are rare and random events. Thus, it is highly unlikely that other mammals would have these same redundant pseudogenes in the same chromosomal locations, with the same mutations that cripple their normal functions. For instance, it is essentially impossible for mice to carry the 21-hydroxylase pseudogenes, in the same genomic location, with the same eight base-pair deletion that destroys its enzymatic function.
Furthermore, once a gene is duplicated and mutations render it a redundant pseudogene, it is inherited by all descendents. Thus, once certain organisms are found that carry the same pseudogene, common descent requires that all organisms phylogenetically intermediate must also carry that pseudogene. For example, suppose we find that humans and old world monkeys share a certain redundant pseudogene. According to common descent, all apes (including chimpanzees, gorillas, orangutans, and siamangs) must also necessarily carry that same redundant pseudogene in the same chromosomal location. This conclusion rests on the premise that there are no mechanisms for removing pseudogenes from genomes (or that the mechanisms are very inefficient). This apparently is true for vertebrates, but some organisms with short generation times, such as bacteria, protists, and Drosophila are known to have mechanisms that remove excess DNA.
Note that, though pseudogenes are curious because they are usually non-functional, this confirmation and potential falsification are independent of whether a specific pseudogene has a function or whether it is completely non-functional, for the same reasons explained in the prediction on morphological vestiges. Like any other genetic element, evolutionary opportunism may occasionally take a pseudogene and press it into a new and different function.
for each of you.
