Molecular Evidence 4: Redundant Pseudogenes
The fourth piece of evidence is from redundant pseudogenes.
A pseudogene is very similar to a regular gene at the DNA level, but with one crucial difference- it never gets transcribed. You can think of a pseudogene as a vestigial molecular structure- sort of like how the appendix is a vestigial organ in humans. Vestigial means that a structure is in degenerate, or atrophied, or somehow imperfect state. For example, the human appendix is basically a degenerate cecum, which is an essential digestive organ in mammals which eat lots of plant matter. You can get along fine without your appendix, but we still have them as an evolutionary carryover from a more herbivorous ancestor.
In the same way, pseudogenes are evolutionary carryovers from our ancestors, and we have them for a few different reasons. The first kind of pseudogenes are called “processed” pseudogenes. You’ll remember from last week’s episode that there are important enzymes used by retrotransposons, which allow them to copy and paste themselves throughout the genome. These enzymes, reverse transcriptase, and integrase, function by taking an RNA transcript, which is a copy of the original gene, and copying it back into a DNA form, which is then integrated back into the genome. This process is beneficial to retrotransposons, since it’s the only way that they can proliferate. But the same enzymes that work on retrotransposon RNA transcripts can work on other RNA transcripts as well. Since all genes are transcribed from the genome into RNA transcripts, there is the potential for reverse transcriptase and integrase to take a random RNA transcript, turn it back into DNA, and stick it back in the genome somewhere. Now, you might think, great, extra copies of a gene! That’s got to be a good thing, right? Well, not really. You’ll remember from the Junk DNA episode that I talked about regulatory sequences that exist in the noncoding DNA surrounding a gene. These regulatory sequences are actually quite important, and without them, you don’t get proper expression of a gene. Since integrase is fairly random in the way that it inserts DNA into the genome, what you end up with is a copy of the original gene stuck in a place that is of absolutely no value- it can’t be expressed there, since there aren’t the proper regulatory sequences.
The second way that pseudogenes can form is through gene duplication. This process occurs through improper recombination of chromosomes during the reproductive process called “meiosis,” which is necessary for sexual reproduction. Most organisms are considered “diploid,” which means that they have two copies of each chromosome. For sexual reproduction, the number of chromosomes in a germ cell has to be reduced to one copy for each chromosome, and meiosis accomplishes this through a mechanism that I won’t detail just yet. One of the stages in meiosis involves recombination between both copies of a chromosome before they’re separated, during which each can swap DNA sequences with the other. Picture two identical twin girls, one wearing a blue headband and one wearing a red headband. If they were to exchange headbands, they’d look basically the same, except for that one small change. That’s similar to what happens with chromosomes, in which sister chromatids exchange DNA. But sometimes mistakes can happen, and the exchange isn’t completely equal. Imagine the twin girls again, exchanging headbands, but only one girl is able to make the exchange. What you’d end up with is one girl with no headbands, and the other girl with two. For chromatids, this means that sometimes one can end up with two copies of a gene, which can get passed on to future generations. In addition to chromosomal recombination errors, sometimes whole chromosomes can be doubled, again due to a problem with the meiosis mechanism. This kind of thing rarely happens in animals, and is usually very detrimental. Down Syndrome is also known as Trisomy 21, which means that an extra copy of Chromosome 21 is present and causes developmental problems. Chromosome duplication, also known as polyloidy, is more common in plants. Recently, evidence has been found that long segments of the human genome exist as replications, although the mechanism for this process is unknown. Whatever the case, be it recombination or segmental duplication, these duplicate genes represent a pretty significant portion of the genome- over 15,000 duplicate genes according to a recent review out of the University of Michigan, which is close to 2/5 of all genes.
The final way that a pseudogene can arise is through evolutionary forces. Just like the ancestral cecum shrank down into an appendix because the evolutionary necessity of having a way to digest a large volume of plant matter was no longer present in human evolution, the lack of selective pressure for a particular gene can make it more likely that mutations and other changes can occur without sacrificing evolutionary vigor. To borrow from the cliché, “if you don’t use it, you lose it.” For an essential gene, a mutation that causes it not to work is likely fatal, or at least decreases the ability of that organism to procreate. Either way, mutations in essential genes have a hard time staying in a population. But if a gene isn’t necessary- let’s say, a gene that synthesizes an essential molecule in a population where that same molecule is available in abundance in the common food sources. In that case, mutations that disable that gene aren’t any more likely to occur on an individual basis, but they are more likely to increase in frequency within the population because there’s no selective pressure to maintain a fully-functioning gene. You’ve probably already guessed this, but this is the reason why duplicated genes often become pseudogenes- if you have two copies of an essential gene, there’s no selective pressure to keep both of them free from mutations- you only need the one. This is why many pseudogenes are found in close proximity to fully functional copies of the normal gene- there’s no pressure to keep both copies functional.
So why is this relevant? Well, for one thing, the formation of pseudogenes is controlled by random processes, whether by retropositioning or duplication. So there’s no good reason why two completely different organisms would have the same pseudogenes in the same genomic locations… other than common heredity. But wait, there’s more! Because of the fact that pseudogenes are largely nonfunctional, they pick up mutations at about the same rate as other noncoding DNA. And as you already know, the acquisition of individual mutations is itself a random process, so there would be even less reason for different organisms to have identical pseudogenes in the same locations with the same mutations… other than common heredity. So let’s look at the evidence.
There are, in fact, many shared pseudogenes between humans and primates, including the enolase pseudogene, hemoglobin pseudogene, sulfatase pseudogene, and the steroid 21-hydroxylase pseudogene. In this last pseudogene, an 8-nucleotide deletion has been found in both the human and the chimpanzee versions of the pseudogene, which in both is responsible for deactivating the gene function. Outside of common ancestry, there is no reason why humans and chimpanzees would share the same pseudogenes, and especially no reason why they would share the same inactivating mutations. This evidence strongly supports evolutionary theory.