Deleting "Junk DNA" - Does it Matter?
03/09/12 07:41 PM Filed in: Intelligent Design|Evolutionary Mechanisms|Human Origins|Human Genetics|Junk DNA
Does deleting "Junk DNA" in laboratory studies, such as in mice make a difference? Interestingly, a colleague of mine just recently pointed out a paper in which exactly this type of research was undertaken. In fact the study is a few years old, and was done in 2004. However, after a search of the literature, I have not been able to find anything similar.
Because this paper, however, shows up prominently on the web as some sort of proof for “Junk DNA”. I felt that a brief review of the facts that were actually discovered in the research are in order.
First, a few brief comments on “Junk DNA” are in order. Less than 5% of the human and other mammalian genomes, like mouse, contain DNA that directly codes for protein. These protein coding segments contain the areas of chromosomes that are traditionally recognized as genes. Because scientists originally did not understand what the non-coding parts of the genome did, they labeled it as junk, hence the term “Junk DNA”.
However, over several decades of research have shown that the non-coding parts of the genome contain a wide diversity of DNA sequence that for the most part, plays a key roles in the development, growth and physiology of an organism. In fact, Dr. Jonathan Wells recently published an outstanding book covering the whole range of issues associated with this field of genetics called “The Myth of Junk DNA”. I highly recommend this book to anyone interested in this issue.
Highlighting the importance of non-coding DNA discovery in the news for 2012, I also recently published a blog post describing how a certain class of retrolements are key in the initial stages of mouse embryo development (link).
The 2004 paper in question is titled “Megabase deletions of gene deserts result in viable mice”, which is unfortunate, because it is somewhat miss-leading. One segment of deleted mouse DNA was 1.5 million bases and the other was 845,000 bases in length. The first impression from the title of the paper makes it sound like they were making multiple megabase-sized deletions all over the genome. Nevertheless, these are two large chunks of DNA. The mouse genome in total is similar to the size of the human genome at about 3 billion bases.
These segments of mouse DNA were chosen because they contained areas of the genome called “gene deserts” - meaning they were completely devoid of not only protein-coding gene sequences, but also contained very few transposable elements and other active regulatory DNA sequence. Interestingly, these two deleted regions did, however, contain over 1,200 “ultra-conserved elements” highly similar to their counterparts in human. See my previous post on ultra-conserved elements and their anti-evolutionary properties here.
Ultra-conserved elements are profound evolutionary enigmas - profound Darwinian DNA contradictions. They are highly similar (conserved) chunks of DNA across mammals (e.g. humans, rats, mice), but presently appear to show very little function (some minor enhancer activity). Hence they should be highly variable between major types of mammals, since very little hypothetical selection is acting upon them (neutral DNA).
Nevertheless, the researchers chose these segments to delete using biotechnology DNA tools because of their lack of supposed functionality. They eventually created strains of mice homozygous for the deletions, but did not perform long-term evaluations of multiple generations. To test the effects of deleting the DNA, the researchers observed both embryological development and mice for 25 weeks after birth. Parameters tested included visual appearance, growth rate, organ pathology, and blood plasma profiles. Apparently all of the visually evaluated parameters and blood profiles were normal.
The researchers also evaluated expression changes (RNA profiles) for 9 genes flanking the deletions for 12 different organs. While a number of expression levels showed possible effects, only two were statistically significant. In fact, they were markedly different for two genes, one in the brain and the other in heart tissue. Since these are two of the most critical organs in the body, the regions that were deleted obviously played some major role of importance and were not just useless chunks of DNA. Also keep in mind that only 12 organs were tested and the researchers did not state the age of the mice tested. Presumably they were adults. Gene expression does vary markedly with the developmental stage of an organ.
The effects of the DNA deletions were also not done under natural conditions where the mice would be living in the wild. Also, the mice were not stressed in any way - often genes only kick in under certain stresses and stimuli. Additionally, did the brain expression changes affect the mice mentally – how would you test that?
The researchers do give the following disclaimer: “In assessing the impact of these deletions on the engineered mice, it is important to acknowledge that our ability to phenotype an organism will always miss some features no matter how detailed. It is possible, even likely, that the animals carrying the megabase-long genomic deletions do harbour abnormalities undetected in our assays, which might impact their fitness, in some other time scale or setting than the ones assayed in this study.”
The bottom line is that gene expression was altered in these mice in very important organs - the brain and heart. Perhaps these areas of the genome where not essential to life, but they were part of God’s created design. Although we have five fingers on each hand, all fingers are not essential to existence, but they are key to an optimal existence. The same is true for nearly all regions of the genome.
Far from showing the uselessness of certain non-coding regions of the genome, this study actually shows how even deleting seemingly gene desert regions has an effect on gene expression. Also, the fact that these regions contain the evolutionary enigmatic pieces of DNA called ultra-conserved elements further indicates that something important is contained therein. Contrary to the hype, this research is just more evidence for intelligent and optimized design in living systems.