<i>Nature</i> Paper Shows "Junk-RNA" Going the Same Direction as "Junk-DNA" - Evolution News & Views


Evolution News and Views



The Nature article, titled, "Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals," finds that rather than being "transcriptional noise," over 95% of the non-coding RNAs studied in the paper show "clear evolutionary conservation." That's another way of saying that their sequences are more similar than would be expected if they were functionless and their encoding DNA was accumulating neutral mutations at a constant rate. After all, if such RNA has no function, you can mutate their encoding DNA with no negative consequences to the organism. But if they have function, then mutations in their encoding DNA would tend to be highly deleterious. By finding that they have highly similar sequences, we find evidence of stabilizing selection, which is strong evidence of function. The abstract of the article is worth reading in full:

There is growing recognition that mammalian cells produce many thousands of large intergenic transcripts1--4. However, the functional significance of these transcripts has been particularly controversial. Although there are some well-characterized examples, most (.95%) show little evidence of evolutionary conservation and have been suggested to represent transcriptional noise5,6. Here we report a new approach to identifying large non-coding RNAs using chromatin-state maps to discover discrete transcriptional units intervening known protein-coding loci. Our approach identified 1,600 large multi-exonic RNAs across four mouse cell types. In sharp contrast to previous collections, these large intervening non-coding RNAs (lincRNAs) show strong purifying selection in their genomic loci, exonic sequences and promoter regions, with greater than 95% showing clear evolutionary conservation. We also developed a functional genomics approach that assigns putative functions to each lincRNA, demonstrating a diverse range of roles for lincRNAs in processes from embryonic stem cell pluripotency to cell proliferation. We obtained independent functional validation for the predictions for over 100 lincRNAs, using cell-based assays. In particular, we demonstrate that specific lincRNAs are transcriptionally regulated by key transcription factors in these processes such as p53, NFkB, Sox2, Oct4 (also known as Pou5f1) and Nanog. Together, these results define a unique collection of functional lincRNAs that are highly conserved and implicated in diverse biological processes.

(Guttman et al., "Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals," Nature, Vol. 458:223-227 (March 12, 2009).)

The article makes an extremely important point: "Strictly speaking, the absence of evolutionary conservation cannot prove the absence of function." This is important because in his book, The Language of God, theistic evolutionist Francis Collins argues that a greater level of differences among species' non-coding DNA than among their protein-coding DNA serves as evidence that the non-coding DNA is "junk." The alternative, of course, is that the large differences within non-coding DNA serve important functions that may actually help determine the differences between species themselves. In other words, the genetic holy grail -- the differences in DNA that determine differences between species -- was staring Collins in the face and he dismissed it as genetic junk. This shows how the "junk" DNA paradigm is deeply embedded within Darwinian thinking, and can serve to stifle scientific advance.

Collins could have used the advice of this Nature paper, which warns that a lack of conservation does not necessarily imply a lack of function. For details on Collins' mistake, see "A Reply to Francis Collins's Darwinian Arguments for Common Ancestry of Apes and Humans."

In closing, the Nature article is a wonderful study on testing function for so-called junk-RNA by knocking out the RNA and assessing whether there is any deleterious effect on the organism (in this case, a mouse). The article states:

The ultimate proof-of-function will be to demonstrate that RNAinterference-mediated knockout of each lincRNAs has the predicted phenotypic consequences. Towards this end, we examined a recently published short hairpin RNA screen of (presumed) protein-coding genes to identify genes that regulate cell proliferation rates in mouse ESCs29. The screen involved genes and some unidentified transcripts that had been identified as expressed in ESCs and showing rapid decrease in expression after retinoic acid treatment. Of the top ten hits in the screen, one corresponded to a gene of unknown function. We discovered that this gene corresponds to one of our lincRNAs (located,181 kb from Enc1) contained in both the 'cell cycle and cell proliferation' cluster (FDR,0.001) and the 'ESC' cluster (FDR,0.001; Supplementary Fig. 9 and Supplementary Table 16). This provides functional confirmation that this lincRNA has a direct role in cell proliferation in ESCs, consistent with the analysis above.
The paper ends by suspecting much function for these non-coding RNAs:
"we speculate that many lincRNAs may be involved in transcriptional control--perhaps by guiding chromatin remodelling proteins to target loci--and that some transcription factors and lincRNAs may act together, with the transcription factor activating a transcriptional program and the lincRNA repressing a previous transcriptional program"
Under the Darwinian vision that our bodies are the result of unguided and clumsy evolutionary processes, Larry Moran supported junk-RNA by proclaiming, "The take-home lesson here is that you can't assume that some region of genomic DNA is functional just because it's transcribed." As an ID proponent, I'm still waiting for Darwinists to let go of their precious "junk" arguments for blind evolution and common descent and learn the lesson that you can't assume that if we don't yet see function for a biomolecule, then it's probably just "junk."