Is There “Junk” in Your Genome? Part 3

| By on Letters to the Duchess

One of the challenges for discussing evolution within evangelical Christian circles is that there is widespread confusion about how evolution actually works. In this (intermittent) series, I discuss aspects of evolution that are commonly misunderstood in the Christian community. In this third of several posts on “junk DNA,” we explore how a specific form of pseudogenes called “processed pseudogenes” arise within genomes.

“Pseudogenes” (literally “false genes”) are generally viewed as sequences in genomes that, though they have high sequence similarity to “real” genes, do not have a function. Historically they were found before the advent of whole-genome sequencing as alternate forms of genes that lacked certain features. Some pseudogenes have characteristics that indicate they are derived from “real” genes – a class of pseudogenes called processed pseudogenes. In this post we’ll discuss the mechanism by which processed pseudogenes arise, and then discuss how a small fraction of them pick up functions and become “real” themselves.

Some assembly required

Processed pseudogenes arise from gene sequences that are transcribed into RNA, and spliced together to form “messenger RNA,” or mRNA, which is what the cell uses to guide protein translation. While I discussed how genes work in the last post in this series, let’s briefly revisit the topic with a view to certain details that we’ll need to understand how processed pseudogenes come to be.

Genes are segments of DNA on chromosomes housed in the nucleus of the cell. In order to make a specific protein encoded by the gene, a “working copy” of the sequence is transcribed into RNA, which for our purposes you can think of as a single-stranded version of DNA (DNA being double-stranded, of course). This RNA copy is thenprocessed to remove sequences that interrupt the protein sequence code. These sequences are called introns, and they are spliced out of the RNA to produce what is called “messenger RNA” or “mRNA” – since it is now ready to carry the protein sequence code, or “message” out to the place where the protein will actually be constructed (outside the nucleus, in the cytoplasm).

While mRNA is a single-stranded molecule, an enzyme called reverse transcriptase is capable of re-creating a double-stranded DNA copy of it. This enzyme function is not a normal cellular function, since the point of producing mRNA in the first place is to make protein, not DNA. Cells don’t need to make DNA copies of RNA transcripts.

So, why is there reverse transcriptase present in cells at all? The answer, as it turns out, is that this enzyme is part of a type of transposon found in many organisms. We discussed transposons in a previous post in this series. In brief, transposons are self-replicating DNA segments that copy themselves and spread within genomes – a sort of minimalist DNA parasite. One class of transposons called retrotransposons copy themselves into RNA and then back into DNA using reverse transcriptase – so this enzyme is present in cells as a result. On occasion, reverse transcriptase makes a DNA copy of a host cell mRNA instead of its intended target (the transposon RNA):

This DNA copy of the mRNA may, at a low frequency, re-enter the nucleus and insert itself into a chromosome. The result is a sequence that is highly similar to the original gene, but lacking several key components: introns are missing, obviously, but also the original “parent gene” chromosomal DNA regulatory sequences. Processed pseudogenes, when inserted, have no function the cell requires – indeed, the cell was getting along just fine without it before it inserted. Accordingly, the vast majority of processed pseudogenes in genomes are not under natural selection, but may mutate freely without consequence.

Seeking the living among the dead

For a tiny fraction of processed pseudogenes, however, this may not be the end of the story. As we saw previously for transposon insertions, in rare cases the arrival of new DNA sequence at a chromosomal location might alter a cellular function and then be selected for on that basis. So to in this example, with an added twist: the fact that the processed pseudogene and its “parent gene” share a great deal of sequence in common raises the possibility that they could interact as RNA copies. If the processed pseudogene lands in a chromosome location that has regulatory sequences nearby, it might be transcribed into RNA as a result. If this happens, the interactions between the two RNA molecules may alter the regulation of the parent gene. If this new interaction has a selectable benefit, the processed pseudogene in effect has become a new gene in its own right and future mutation and selection may hone this nascent function over time.

As we mentioned previously, the fact that transposons can be converted into functional sequences does not “confer” functionality on all transposons. Nor does the (very interesting) finding that “the dead may rise” from pseudogene to gene indicate that all processed pseudogenes are likewise functional or about to become so. Rather, both examples illustrate that new biological information can be obtained through the natural processes of mutation (in this case, duplication and insertion of DNA sequence to a new location in the genome) and subsequent selection.

In the next installment of this series, we’ll examine one final form of non-functional DNA present in genomes, and one that is of great discomfort to antievolutionary views: unitary pseudogenes.


References & Credits

Further reading

Esnault, C., Maestre, J., and Heidmann, T. (2000). Human LINE retrotransposons generate processed pseudogenes. Nature Genetics (24); 363 – 367.

Zheng, D., and Gerstein, M.B. (2007). The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends in Genetics (23); 219 – 224.

About the Author

Dennis Venema

Dennis Venema is professor of biology at Trinity Western University in Langley, British Columbia and Fellow of Biology for BioLogos. He holds a B.Sc. (with Honors) from the University of British Columbia (1996), and received his Ph.D. from the University of British Columbia in 2003. His research is focused on the genetics of pattern formation and signaling using the common fruit fly Drosophila melanogaster as a model organism. Dennis is a gifted thinker and writer on matters of science and faith, but also an award-winning biology teacher—he won the 2008 College Biology Teaching Award from the National Association of Biology Teachers. He and his family enjoy numerous outdoor activities that the Canadian Pacific coast region has to offer. 

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