Treasure in the Genetic Goldmine: PZ Myers Fails on “Junk DNA”

_{Jonathan McLatchie

December 19, 2011

Intelligent Design}

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Readers may recall my encounter with developmental biology professor PZ Myers earlier this year. In that brief interaction, I came to appreciate Myers’s ability to charm his adoring fans and followers irrespective of the scientific robustness of his claims, or the accuracy with which he represents the views of those with whom he disagrees.

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All introns have at least ONE function-> to separate exons to allow for alternative gene splicing. Differences in introns- those non-conserved areas, could either be species specific or just physical space to hold data (as RAM does in a computer).Joe_{December 20, 2011
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paulmc: I think you are really misrepresenting the situation. Here is the beginning of Sorek and Start's paper: "The recently published draft sequence of the mouse genome (Waterston et al. 2002) facilitates a great advance in searching for cis-regulatory sequence elements. The 75 million years that have passed since the divergence of the ancestor of the human and mouse lineages allowed a substantial divergence in neutral DNA; the constraint on functional elements has kept them conserved. Indeed, homologous human and mouse exons are, on the average, 85% identical in their sequences, but introns are more poorly conserved: 60% of the nonexonic sequences are nonalignable, and in the alignable regions the average identity level is 69% (Waterston et al. 2002). However, numerous regions that are conserved between human and mouse are also found in introns (Hardison et al. 1997). Comparison between the human chromosome 21 and the corresponding genomic sequences in mouse revealed that only one-third of the conserved blocks are exons (Dermitzakis et al. 2002). The other two-thirds of highly conserved sequences are intronic and intergenic. These conserved elements were found to be unexpressed in microarray experiments. Thus, the conclusion was that they are probably cisregulatory sequence elements, but no function could be assigned to most of them (Dermitzakis et al. 2002). We decided to check the possible correlation between the conserved intronic sequences and alternative splicing regulation." As you can see, things are a little bit different from what you stated. It is true that introns show in general less conservation than exons, but 40% of intron sequence shows some conservation, and two-thirds of highly conserved sequences are intronic and intergenic. I would not say that this equals to "the overwhelming majority of intronic sequences lack the sequence conservation indicative of function". As can be seen form what I quoted, a significant part of introns, even if not the majority, shows conservation. Sorek and Ast just chose to concentrate their work on the possible function in alternative splicing of the regions flanking exons. moreover, as the function of non coding DNA in general, and of introns in particular, is probably mainly regulatory, it is perfectly possible that they can change more fron one species to anothers one than proten coding segments for functional reasons. It is extremely likely, indeed, that the differences between species, especially at the high end of evolution (we are discussing human and mouse here), are mainly regulatory, rather than mediated by big differences in the effectory protein genes. So, while good conservation almost certainly denotes function, we cannot assume that lower conservation equals lack of function, as we can see in the approach to the search of specific human functional genes by looking for HARs.gpuccio_{December 20, 2011
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Jonathan, we need to look a little more closely at Sorek and Ast (2003) here. We should be careful to not that they observed conserved regions of introns, and not that the entire intron is conserved, as one could conclude from what you've written. They note we are talking about "103 bases in the upstream intron and 94 bases in the downstream intron". Introns within human coding sequences average 3,749 bp (Hong et al. 2006). Even if these conserved stretches occurred in all genes (instead of a minority of genes), this is still a trifling proportion of the intron sequence. Hence, we need to be clear here that there are small islands of function in introns - and of course there are lots of other examples of functional intronic tidbits than the one discussed here. But let's keep this in perspective - the overwhelming majority of intronic sequences 1) lack any known function, 2) lack the sequence conservation indicative of function, 3) occur without evidence of facilitating alternative splicing, and 4) accumulate in species with sufficiently small population sizes that they are unable to remove all slightly deleterious mutations (such as intronic expansions).paulmc_{December 19, 2011
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Excellent summary of important findings. Thanks Jonathan M.PaV_{December 19, 2011
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