One person’s junk is another’s treasure

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In previous essays (here and here), we learned that genes encoding new proteins can and do, often, arise de novo in the course of evolution, contradicting one of the central tenets of ID proponents. The means by which these genes arise are many. One of these, suggested by Cai at al. (the subject of one of the earlier essays), involved the adaptation of a gene encoding an evolutionarily-conserved non-coding RNA via the appearance, by mutation, of appropriate translation initiation and termination (“start” and “stop”) codons. This mechanism represents an intersection of sorts between the subject of protein evolution and another matter of discussion on these blogs, namely the existence, evolution, and “function” of junk DNA. In this essay, I review a 2007 study by Debrah Thompson and Roy Parker (“Cytoplasmic decay of intergenic transcripts in Saccharomyces cerevisiae”, Mol. Cell. Biol. 27, 92-101) that adds a great deal of clarity to this mode of gene and protein evolution.

To begin this review, it helps to refresh our memories with respect to a previous essay. In this essay, we learned of a class of RNAs in Saccharomyces cerevisiae that were termed “cryptic unstable transcripts” (or CUTs). These RNAs were uncovered by analysis of mutants defective in the functioning of the nuclear exosome, a complex responsible for the degradation of RNA; they were typified as transcripts whose abundances were dramatically increased by mutational disruption of the nuclear exosome. Thompson and Parker extended the study of CUTs by studying the contributions of other degrading mechanisms to the production and accumulation of CUTs. The basic strategy of the study was similar to earlier ones – compare and assess the levels of CUTs in yeast strains that carry mutations that affect other RNA degrading processes. In addition to the nuclear exosome, these processes include the decapping (1) of mRNAs in the cytoplasm, degradation of the mRNA from the 5’ end by the Xrn1 exonuclease, and nonsense-mediated decay (2) of mRNAs (abbreviated hereafter as NMD).

One outcome of the experiments described by Thompson and Parker was the identification of a number of subclasses of CUTs (see the following figure, which is Fig. 4 from Thompson and Parker). Thus, some CUTS had the characteristic that their steady-state levels were increased by mutation of the nuclear exosome, but not components of the cytoplasmic RNA degradation and NMD systems. This is consistent with earlier studies; however, the proportion of CUTs that fell into this class was small (13% of those studied). A much larger number (83%) were affected by mutations in the cytoplasmic RNA turnover complexes, including many (40%) that were affected by mutations in the NMD machinery. These results are important, as they indicate that a majority of CUTs are available for degradation in the cytoplasm as well as in the nucleus.

Thompson and Parker Fig4.jpeg

(In this figure, the nuclear exosome is “queried” by the rrp6 mutation, and cytoplasmic turnover by the dcp1 and xrn1 mutations; NMD is self-explanatory.)

The effects of mutations in the NMD complex are significant for yet another reason. NMD not only occurs in the cytoplasm, it also requires that the target RNAs be able to be translated. This is an unexpected property of CUTs, as they do not possess long open reading frames (a defining property of most translated mRNAs). Accordingly, Thompson and Parker studied the association of CUTs with polyribosomes (3). The results were clear – CUTs in fact may be found in polyribosomes, indicating that they can be “translated” by the translation machinery. (The results of this study are in Fig. 6 of the paper by Thompson and Parker.)

These experiments reveal an unexpected diversity in the mechanisms of mRNA quality control in the cell. However, they also provide an interesting snapshot into the path by which “junk” RNA may evolve into a moiety that encodes a functional protein (such as BSC4). This pathway is described in Fig. 7 of the paper by Thompson and Parker (see below). As the authors put it:

The ability of “noncoding” intergenic transcripts to enter translation suggests a possible mechanism whereby new ORFs encoded by bona fide mRNAs might arise (Fig. 7). First, a noncoding intergenic transcript would be produced by RNA Pol II. Note that in many cases fortuitous intergenic transcription might arise simply due to the bidirectional nature of eukaryotic transcriptional enhancers. For example, NEL025c lies head to head with the gene DLD3. Between them are two palindromic transcription factor binding sites, which mediate a response to available nitrogen sources (6, 23). We have shown that NEL025c levels respond to nitrogen source in a manner similar to that of DLD3 (data not shown) (23). Second, these intergenic transcripts would gain a 3’ end, either by normal polyadenylation or potentially by other methods for 3’-end generation. Not only would intergenic transcripts that gained a normal poly(A) tail be good substrates for nuclear export, but once exported, the capped and adenylated RNA would be expected to engage the cytoplasmic translation machinery. Intergenic transcripts producing an advantageous polypeptide would then be subjected to natural selection, allowing further evolution into a bona fide mRNA with a functional ORF. Thus, intergenic transcripts may not simply be genomic noise but may also be a factor of adaptive mechanisms requiring variation and selection, thus providing fodder for the evolution of new ORFs.”

Thompson and Parker Fig7.jpeg

Importantly, none of these steps is a necessarily “high-information” one (to adopt the terminology of ID proponents), but rather are well within the reach of random mutation and natural selection.

To summarize, this study adds yet another set of data to the collection that shows how readily new genes may arise. It also brings together some different areas (protein evolution, mRNA turnover) in a most interesting and provocative manner.

Citation:

Thompson, D.M., Parker, R. (2007). Cytoplasmic Decay of Intergenic Transcripts in Saccharomyces cerevisiae. Molecular and Cellular Biology, 27(1), 92-101. DOI: 10.1128/MCB.01023-06

Footnotes:

1. As explained here and here, eukaryotic mRNAs possess a distinctive chemical structure at their 5’-ends that is called the cap. This cap must be removed before the mRNA can be degraded from its 5’ end by 5’->3’ exonucleases.

2. One of the quality control mechanisms that operate to reduce the contributions of errors to the goings-on of the cell involves the recognition and degradation of mRNAs that possess premature stop codons (also commonly known as nonsense codons, as they arise by the mutational conversion of codons that specify amino acids with one of the three stop codons). Truncated proteins encoded by mRNAs with premature stop codons are disposed to possess undesirable characteristics, such as being unfolded or capable of non-productively interacting with other proteins in a cell. NMD reduces these contributions, and thus helps to counter the effects of mutation and misincorporation during transcription.

3. Polyribosomes are complexes that consist of mRNAs and their associated translating ribosomes; they are termed “polyribosomes” because more than one ribosome is associated with each mRNA. They can be isolated and characterized by density gradient centrifugation.

4. This essay may also be found here.

12 Comments

Of course, to me the most interesting question about this study is whether features of the eukaryotic genome can be explained as adaptations which facilitate the creation of new genes through this mechanism. For instance, are eukaryotic promoters commonly palindromic because eukaryotes with palindromic promoters produce new genes more quickly?

Anyway, just skimmed the research article, so I hope this line of discussion isn’t too inane.

My personal hypothesis with regards to palindromic promoters is that it was a relatively easy target for other proteins to hit because of the symmetry. You could take one small domain that had an affinity for half the sequence and doubling seems to be a common mechanism. In general though I think these kinds of evolovability hypotheses and arguments are interesting even if they do demand incredibly challenging experimental designs to test effectively.

JGB said: My personal hypothesis with regards to palindromic promoters is that it was a relatively easy target for other proteins to hit because of the symmetry. You could take one small domain that had an affinity for half the sequence and doubling seems to be a common mechanism.

So are you saying that head-to-head or tail-to-tail (“palindromic”) doubling is more likely than head-to-tail (“sequential”) doubling? If so, how much more likely? (Just asking.)

Palindromic promoters aren’t all that common. Spend some time with the genome browser at http://www.genome.ucsc.edu/ When they do occur you have to suspect that one of the genes arose from upstream non-coding sequence. I haven’t a clue of whether or not that is often the case, but the UCSC browser would let you make a study of it. Look at the conservation of the sequence region, and how expression in both directions is conserved.

It’s not an issue of the doubling by preferential one way or the other as far as I know. It has more to do with the tail to tail would be an easy to spot product, which is related to Mike’s comment. I certainly haven’t studied the issue in any depth, but based on doubling being a relatively common mechanism it is an attractive argument.

Highly neat series all around; informative with a side order of revealing yet another creationist mistake in their long series caused by assuming the result.

But I’m sure this nitpick has been mentioned many times before:

none of these steps is a necessarily “high-information” one (to adopt the terminology of ID proponents), but rather are well within the reach of random mutation and natural selection.

The ID terminology is nonsense, and contradicts information theory usage. Basic information measures such as Shannon information or algorithmic information are maximized by noise. So from that view mutation, translation, and transcription noise are all part of a high information environment.

AFAIU selection forms functions by paring down the information theoretical content of what that environment contributes.

OTOH, intended as a description of coarse-grained high-level information of complexity or whatever, what IMHO pops out to the reader of the series of articles is that those evolutionary mechanisms really works on all of the underlying fine-grained actual chemical functions taking place. “Divide and conquer”, “evolution as tinkerer”, et cetera.

(Dope slap) Of course there are studies easily googled, and its not all that uncommon in the human genome. 10%. http://www.genome.org/cgi/reprint/14/1/62.pdf Now looking at the first example in their supplemental table 2, isocitrate dehydrogenase 3 gamma and SFRS protein kinase 3 on X, on the UCSC browser you can see conservation in mammalian genomes, but isocitrate dehydrogense 3 gamma vanishes in nonmammalian sequence. There seem to be a number of isocitrate dehydrogenase isoforms on other chromosomes. Wonder if they’re convergent or divergent?

Mike said:

(Dope slap) Of course there are studies easily googled, and its not all that uncommon in the human genome. 10%. http://www.genome.org/cgi/reprint/14/1/62.pdf Now looking at the first example in their supplemental table 2, isocitrate dehydrogenase 3 gamma and SFRS protein kinase 3 on X, on the UCSC browser you can see conservation in mammalian genomes, but isocitrate dehydrogense 3 gamma vanishes in nonmammalian sequence. There seem to be a number of isocitrate dehydrogenase isoforms on other chromosomes. Wonder if they’re convergent or divergent?

I feel like Jane Goodall, observing the molecular biology tribe at play. “They’re grooming now … “

White Rabbit (Greg Goebel) http://www.vectorsite.net/tadarwin.html

Torbjörn,

Thanks for the kind remarks. Of course you are correct about the IDists’ abuse of information theory. This is why I couched the term with quotation marks. ID proponents have many and sundry euphemisms for “evolution didn’t do it” or “beyond the reach of natural mechanisms”, and “high-information” is unfortunately one of the more widely-used of these. Hopefully, my sloppiness does not confuse the main issue - that the ID position about the origins of new genes is just plain wrong.

Arthur,

Another fine essay, thanks. Speaking of information, I was enjoying your discussions with Kirk Durston at Recursivity. Will you be returning to them?

For anyone else interested:

http://recursed.blogspot.com/2008/0[…]ientist.html

SteveF,

Thanks. I’ll be continuing my discussion with Kirk, if at a somewhat leisurely pace. We’ll see where that discussion goes.

Art

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This page contains a single entry by Arthur Hunt published on July 23, 2008 12:52 AM.

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