More functions for 'junk DNA' discovered

It's not exactly Ferguson, Mo., but the battle between ENCODE researchers and junk-DNA holdouts goes on. Our ongoing coverage of the hostilities left off with the latter sending over their latest salvo. Now, ENCODE is back. Confident that genomes are not mostly junk, they have set their latest contender in the ring: a mouse.

The mouse genome was sequenced in 2002 as a primary model in which to study gene function and human diseases and to develop drugs. This was followed by maps of transcribed messenger RNA molecules and of long, non-protein-coding RNAs, which facilitated such experiments and analysis. Yet although 17 mouse strains have been sequenced, genome function and regulation cannot be understood by sequence analysis alone. Now, in four papers published in this issue, the Mouse ENCODE Consortium presents data sets that dramatically enhance our understanding of the regulation of the mouse genome, and of the similarities and differences compared with the human genome. (Emphasis added.)

The four papers in announce the findings from the Mouse ENCODE Consortium: The gist of the salient results can be seen from Piero Carninci's summary article in the same issue of , "Genomics: Mice in the ENCODE spotlight."

Surprisingly, the Mouse ENCODE Consortium ... finds that sequences commonly considered useless or harmful, such as retrotransposon elements (stretches of DNA that have been incorporated into chromosomal sequences following reverse transcription from RNA), have species-specific regulatory activity. Because retrotransposon elements can contain embedded transcription-factor binding sites, this may provide unexpected regulatory plasticity... Evolutionary conservation of primary sequence is typically considered synonymous with conserved function, but this finding suggests that this concept should be reinterpreted, because insertions of retrotransposon elements in new genomic regions are not conserved between species.

In short, the Mouse ENCODE group takes direct aim at the arguments of Dan Graur and the other junk-DNA faithful, who say that everything evolution did not conserve is junk.

Here are a few of the other surprising results that Carninci summarizes:

• Most of the differences between human and mouse genes appear in regulatory elements rather than gene sequences.


• Despite the different primary sequences of many regulatory elements, the basic reciprocal regulatory networks among transcription factors are evolutionarily conserved between mice and humans.


• Expression of similar genes is species-specific, not organ-specific.


• Many single-nucleotide changes associated with human disease are found in orthologous regions in the mouse genome.


• Chromosome structures are associated with regulation of gene expression, and they replicate together.

Undoubtedly these findings will lead to a great deal of excited discussion about what they mean for evolution or for intelligent design, but the same basic principle applies to Mouse ENCODE that applied to Human ENCODE: much of what Darwinian evolutionists had dismissed as junk appears functional. Non-coding regions of the mouse genome are transcribed, and appear to function in previously unimagined ways, such as regulation of gene expression, chromosomal stability, and maintenance of species identity. Carninci offers further thoughts:

Analysis of these data will continue, both broadly and in the context of specific biological questions, although new tools for visualizing, analysing and interpreting such data are needed to open them up for broader use by experimental biologists. But the existing findings are already thought-provoking. For example, they suggest that we should rethink the relationship between genomic function and evolutionary conservation. Regulatory regions and long non-coding RNAs (lncRNAs) are not subject to the evolutionary constraints of protein-coding genes, which may help to explain the sequence drifts reported in these papers. However, it is striking that transcription-factor networks are conserved despite low conservation of their binding positions in the genome.

As the junk-DNA advocates try to explain away the new findings, we look forward to evaluating this flood of new data from a design perspective.