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Pseudogenes ~ Page 2































2. Human globin genes.  Hemoglobin is a large molecule in our red blood cells responsible for carrying oxygen.  It has iron as part of its molecule and that is why our blood is red. A single adult hemoglobin molecule consists of two alpha-globins and two beta-globins.  There are five different functional genes (or alleles) for the beta-globin, all on chromosome 11.  However, in the middle of the beta-globin gene cluster is a broken beta gene. We know it is a pseudogene because it is nearly identical to the other beta genes, but it contains a series of errors or mutations that keep it from being transcribed.  An explanation from an antievolutionist might be that there was originally six beta genes and after "The Fall" one was "de-evolved".  But this hypothesis can be tested and fails.  Not only do gorillas and chimps have the same pseudogene in the same location, but all three groups share exactly the same set of mutations: an altered control region, a defective start signal, four 'stop' signals at the same locations, and two identical frameshift deletions.  This is a 'smoking gun' of evolutionary evidence.  All three primates MUST share the same common ancestor; it's the only explanation that makes sense.




The Importance of Pseudogenes


If evolution is true, pseudogenes should have been accumulating in our genome for millions of years and will represent a molecular fossil bed that can be mined for information of our past and our origins. Some will be relics of past genes that were eliminated during evolution and no functional version will exist.  Others will be copies of a gene that has evolved over time and these pseudogenes can be viewed as ancestors to present genes.  Other pseudogenes that are shared between species can point to common ancestry.  When the mouse genome was studied, it was found that 99% of human genes have a corresponding version in the mouse.  Nearly all of the human genome can be lined up against equivalent mouse regions, known as syntenic blocks.  Despite this, only a small fraction of the known human pseudogenes have mouse counterparts. Thus, since we last shared a common ancestor with mice about 75 million years ago, we share few pseudogenes with mice compared to other apes as most of our pseudogenes have been generated relatively recently in geologic time.  


Once disabled, these pseudogenes tend to be no longer under natural selection pressure and will accumulate mutations (exceptions are known). They are said to be neutral in regards to evolution and by studying them, we can estimate the rate at which mutations accumulate. This can give us a molecular clock that can be used to study changes through time in a species’ genome.


Unitary pseudogenes are unprocessed and unlike other pseudogenes, have no functional counterparts. Unlike duplicated pseudogenes, these genes had an established function prior to the mutation that inactivated them.  So far, 76 human unitary pseudogenes have been identified and an additional 11 human genes with pseudogenic alleles have been found.  Examples include the NR1H5 nuclear receptor pseudogene and the chemokine receptor CCR5 gene which are discussed below.  


The NR1H5 pseudogene is present in human, chimpanzee, and rhesus monkeys. Of the 14 disruptive mutations present, three are found in all the mentioned groups and include one frame shift, one splice-junction and one nonsense mutation. Based on DNA sequences from human, mouse, rat, and chicken the inactivation of NR1H5 occurred 42 mya, slightly later than the previous 42.9 mya estimated divergence between the catarrhines (humans, apes, Old World monkeys) and New World monkeys. The concurrence is striking; it is very difficult to impossible for one to argue against common ancestry.


The CCR5 human gene has a pseudogenic allele with a 32 bp deletion. The homozygous person is strongly protected from infection by various pathogens, including HIV. Thus, it also represents an example of a beneficial mutation. A second example of a beneficial mutation is the caspase-12 gene in which carriers are more resistant to severe sepsis.  This particular mutation has spread through most of the human population within the past 100,000 years.


Dead Genes For Tooth Enamel (Jerry Coyne) - Original Paper: PLOS Genetics

Toothless animals that evolved from ancestors with teeth have enamel pseudogene (ENAM) present as predicted. The species can be nested to produce an evolutionary tree that matches the fossil record.



Functional Pseudogenes?


When comparing  interspecies genomes, some pseudogenes appear to be better preserved than others.  Such pseudogenes may be under natural selection after all and thus have hidden functions.  About two dozen examples of pseudogenes that appear to be active in some way have been described.  Results are preliminary but this may actually be an example of nature using broken genes for other functions, similar to the cases where parts of ERVs are thought to contribute to the host genome. In yeast, some pseudogenes appear to be able to be reactivated when environmental conditions change - thus they can serve as a potential genetic reserve in times of change.  


Certainly, it appears that some pseudogenes will probably be confirmed in the future to have functions or to have new functions in their disabled state (through RNA functions for example since they cannot transcribe DNA).  However, the patterns of accumulated mutations and shared pseudogenes across species will speak loudly to common ancestry and the reality of macroevolution. In addition, even if some pseudogenes are confirmed to have functions, at this time it appears doubtful that they would make a significant dent in the 20,000 known and counting human pseudogenes identified to date. The newer concept of pseudogenes are that they have become functionless to their original parental gene, whether they are found to have a new function or not, such as a RNA gene that can feed back on it’s parental gene.  Molecular paleontology has been born and may provide us with more evidence of evolution than even the fossil record has.



Concept of Plagiarism


One way to approach the issue of pseudogenes and common ancestry is to view it as an example of plagiarism. In attempting to decide if two items share a common source one way is to look for errors that may be shared between them.  It is well known that publishers will often introduce into their books some purposeful errors.  In the case of copyright suits the original author can successfully claim copying by the second author if  it can be demonstrated that the same errors exist in both.  Duplicated errors imply copying and this principle is well established in copyright law. The inclusion of false entries in textbooks is one method publishers use to trap potential plagiarizers (see Max).  More recently, computer chip manufacturers also place erroneous code in their chips to protect themselves in the same manner as book publishers.  Lastly, in Miller’s “Only A Theory” he details how he exposed two students for plagiarism when they could not explain how they both had the same errors in their papers.  One might claim that the material could be similar since they were studying together, etc. but the copying errors made that an impossible defense.


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