The classic story regarding the evolution of antibiotic resistance that is taught to students at more-or-less all levels is that the presence of antibiotics - in growth medium, in an infected organism, etc. - kills off the susceptible bacteria, leaving resistant members to survive. More complex versions of this story note that early resistant mutant phenotypes tend to somewhat sensitive to antibiotics, and as more and more generations appear, the resistant phenotypes become more and more resistant, finally culminating in resistance to antibiotics at dosages that are utilized clinically.

Though quaint, plausible, and powerful with respect to explanatory scope, the story is simply not true. It has been known for a good deal of time that most antibiotic resistance genes are acquired and passed to other bacteria via integrons, which are mobile genetic elements that can capture and transfer genes, and subsequently integrate them into other genomes in a site-specific manner. For the most part, antibiotic resistance in bacteria is a consequence of both inter- and intraspecies transfer of non-essential, self-replicating, extrachromosomal collections of genes and other elements of DNA information known as plasmids. An excellent article detailing this information was published in the journal Cell back in March of 2007.The abstract from this article nicely summarizes and supports what is written here (special emphasis added by TRR):

Molecular Mechanisms of Antibacterial Multidrug Resistance Cell 128(6):1037-1050 Michael N. Alekshun and Stuart B. Levy Treatment of infections is compromised worldwide by the emergence of bacteria that are resistant to multiple antibiotics. Although classically attributed to chromosomal mutations, resistance is most commonly associated with extrachromosomal elements acquired from other bacteria in the environment. These include different types of mobile DNA segments, such as plasmids, transposons, and integrons. However, intrinsic mechanisms not commonly specified by mobile elements—such as efflux pumps that expel multiple kinds of antibiotics—are now recognized as major contributors to multidrug resistance in bacteria. Once established, multidrug-resistant organisms persist and spread worldwide, causing clinical failures in the treatment of infections and public health crises.... The means that microbes use to evade antibiotics certainly predate and outnumber the therapeutic interventions themselves. In a recent collection of soil-dwelling Streptomyces (the producers of many clinical therapeutic agents), every organism was multidrug resistant. Most were resistant to at least seven different antibiotics, and the phenotype of some included resistance to 15–21 different drugs...

So... not only is antibiotic resistance, in general, not attributable to mechanisms of Darwinian evolution (random selection of 'more fit' individuals via the influence of some multitude of 'selective forces'), but the mechanisms that microorganisms commonly use existed prior to the use of antibiotics.

This is actually summarized quite nicely in a story (Medical Tribune, 29 December 1988, pp.1, 23, no electronic resource known to be available) about some unfortunate sailors who froze to death on an Arctic expedition back in 1845. The sailors were buried in the permafrost until 1986 when their bodies were exhumed. Given that the sailors had been frozen solid in the permafrost, the bodies were extremely well preserved; in fact, researchers were able to isolate and revive six strains of 19th century bacteria found within the contents of the sailors' intestines. These 19th century bacteria - bacteria that were alive prior to the discovery of penicillin were found to be resistant to several modern-day antibiotics, including penicillin.

Another piece of research has appeared that further corrupts the classic story of the development antibiotic resistance via Darwinian evolution. The abstract is reproduced below:

Integrons are found in the genome of hundreds of environmental bacteria but are mainly known for their role in the capture and spread of antibiotic resistance determinants among Gram-negative pathogens. We report a direct link between this system and the ubiquitous SOS response. We found that LexA controlled expression of most integron integrases and consequently regulated cassette recombination. This regulatory coupling enhanced the potential for cassette swapping and capture in cells under stress, while minimizing cassette rearrangements or loss in constant environments. This finding exposes integrons as integrated adaptive systems and has implications for antibiotic treatment policies.

You got all that, right?

Perhaps not. I'll do the best I can do translate it: This particular article details the molecular mechanism behind the transfer of resistance genes between bacteria. As the article details, it's the use of antibiotics themselves that actually triggers the synthesis of a specific bacterial enzyme that identifies and preferentially captures the resistance genes, and subsequently facilitates their expression. Additionally, this enzyme promotes the rearrangement of these resistance genes. The rearrangement of these genes alters the order of when the genes are expressed. New rearrangements that are triggered by taking an antibiotics, and those bacteria that have 'correctly' rearranged their genes, creating a new resistance cassette, will be able to survive and pass on resistance not only vertically, to subsequent generations, but also horizontally; bacteria can pass resistance genes to their neighbors in a deliberate manner.

This is huge. The classic Darwinian story render the organism entirely a slave to the environment, unable to respond or adapt at the individual level. Only a lucky few - a few that are resistant simply by chance - survive the selective pressure of antibiotic use, and are able to pass on their genes.

Or as you've been more simply taught: Survival of the fittest.

This new research clearly indicates that this is not necessarily the case; indeed, it appears that - contrary to what I've been taught more-or-less through my entire history in science - individual organisms, not just populations are able to react to and adapt to the environment.

Or at least individual microorganisms are able to do this.

It cannot be stressed enough how significant of a break this is from the classic story of antibiotic resistance via Darwinian evolution. The idea that the individual and not just the population of organisms can adapt to a changing environment at the DNA level is literally scientific heresy.

This is of course more evidence, another huge piece of evidence suggesting that The Theory of Evolution with respect Darwin's ideas is at least not as well understood as was once believed, and at most completely, utterly, and totally false.

I just found this article on Bloomberg.com regarding the H1N1 Swine Flu; the article is entitled: "Swine Flu Is Spreading Wider Than Official Data Show (Update2)", and this article is nothing more than scare tactics and sensationalist journalism at its worst. It might take a trained eye to catch some of this stuff and interpret it, but that's what I'm here for. In any case the first little bit of the article reads:

Swine flu is spreading more widely than official figures indicate, with outbreaks in Europe and Asia showing it's gained a foothold in at least three regions.

This first statement is meant to frighten you, meant to lead you in and make you believe that the swine flu is a serious concern - or at least more or a concern than the typical seasonal flu. The italicized portion is the real scare tactic... in reality it's actually quite an innocuous statement, and is explained in the very next paragraph/statement:

One in 20 cases is being officially reported in the U.S., meaning more than 100,000 people have probably been infected nationwide with the new H1N1 flu strain, according to the Centers for Disease Control and Prevention.

Sounds scary, doesn't it? In actuality, it's not only not a bad thing - it is in fact a good thing, and here is why. In my previous swine flu update, I provided some statistics regarding Case Fatality Ratios (CFR's) for not only past 'serious' flu outbreaks, but also for the seasonal flu, and this current swine flu outbreak, rather than reproducing these statistics here it is easier to simply quote this other post:

...the CFR is the best estimate or description of a disease's virulence. Estimates for the CFR of the seasonal flu are approximately 0.1%. The 1918 Spanish Flu Pandemic has been estimated to have a CFR ranging from 2% to 20%, depending on which sources you check, but is most commonly given as 2.5%. This particular virus, depending on which statistics you look at. Considering only the number of deaths per infected individual, the USA, Mexico, and worldwide have CFR's of 0.110%, 1.97%, and 0.78% respectively. These CFR's are likely overestimated as well; it's reasonable to assume that the actual number of cases is higher – probably significantly higher – than the reported number of cases.

As the quote above indictates, the CFR's that I have calculated are actually likely to be overestimated by at least an order of magnitude, or as suggested above as much as 20 times. If I recalculate CFR's based on an underestimate of 20 fold, the numbers as of today for the USA, Mexico, and the entire globe are 0.00739%, 0.09635%, and 0.036525%, respectively. In the worst case scenario, Mexico, based on the most recent swine flu update from the WHO, the approximate CFR is 0.09635%, under the value typically estimated for the seasonal flu. If you read the article a bit further, the prognosis is even more hopeful:

In the U.K., the virus may be 300 times more widespread than health authorities have said, the Independent on Sunday reported yesterday.

Or based on the most recent numbers of 137 cases and 0 reported deaths, the actual and estimated CFR's are zero, given the underestimation of the case number, the number is less than in the US or Mexico when each of those countries had a comparable number of cases 0.709% and 5.769% for the US and Mexico, respectively. Even more good news:

Japan, which has reported the most cases in Asia, began reopening schools at the weekend after health officials said serious medical complications had not emerged in those infected.

The statement that follows attempts to frighten the reader once again:

The virus is now spreading in the community in Australia, Jim Bishop, the nation's chief medical officer, said yesterday. "I think we will see the number rise," Bishop told Australian Broadcasting Corp. radio today after confirming the nation's 17th case and saying test results are pending on 41 others.

The flu virus spreads, and as it spreads, the number of cases rise; this is what's expected of the flu virus, or for the most part, any easily transmitted virus. As the virus makes its way around the planet, more people are infected. Nothing scary about that - or at least nothing more scary than the seasonal flu. The statement that truly drives home the point that - thus far - there is nothing to fear from the dreaded H1N1 swine flu:

Most of those infected experience an illness similar to that of seasonal flu. The main difference is that the new H1N1 strain is persisting outside the Northern Hemisphere winter.

For the most part the rest of the article simply cites statistics about the virus - all of which suggest that this particular virus is of no more concern than the typical seasonal flu.

I've never been fond of the term "junk DNA"; the term seems to be loaded with a staggering degree of presumption and hubris, quite possibly reflecting the omniscient attitudes all too common among some, even many scientists.

Personally, when I teach about this portion eukaryotic genomes, I not only utilize the term "non-coding" DNA, but also generally express my disdain for the term "junk DNA".

To be honest with you, I don't even believe that non-coding DNA is an adequate term. Indeed these particular regions of the genome are not translated, but that doesn't mean the DNA doesn't encode something. For example there are many regions of the genome that are transcribed, but are not translated.... that is these regions of the genome have functionality, but it occurs at the level of RNA, not at the level of protein.

It's often surprising to people who taken a few, biology courses, but believe it or not, there are many more varieties of RNA than the three commonly taught: mRNA, rRNA, and tRNA. Indeed, a wide variety of different RNA, with unique functionalities and specifities have been discovered; wikipedia has a nice list of these different RNA types. Some of these RNAs are universal while others are found in eukaryotes only, and some are found in specific cell types. However this post isn't about RNA; it's about DNA - junk DNA specifically.

Despite the fact that I've entitled this post "More Function for Junk DNA," this is actually my first post in this blog regarding junk DNA, so I'm going to add quite a bit of background information, including a brief history of junk DNA.

The term junk DNA was first coined in 1972 by Susum Ohne, an Asian-American geneticist and evolutionary biologist. Just to be fair to Ohno, the introduction of the unfortunate misnomer junk DNA was not his only contribution to science. Ohno is credited with the discovery that the Barr body present in mammalian female nuclei is in fact a condensed X chromosome. Ohno also authored the classic book Evolution by Gene Duplication, published in 1970, wherein he postulated that gene duplication plays a significant role in evolution. Ohno's law, which postulates that mammalian X chromosomes are conserved among species, is named for this specific Ohno.

What are we talking about when we say junk DNA? Loosely, the term is probably best defined as DNA for which no known function has yet been determined. There are many different regions of the genome that classify as junk DNA; indeed 95% of the human genome does not encode for protein. There is a wide variety of non-coding DNA present in eukaryotic genomes, examples include: pseudogenes, retrotransposons, microsatellites, centromeres, telomeres, introns. Admittedly, some of these regions, telomeres, centromeres, and introns in particular have known functions, but represent non-coding regions of the genome that were not historically understood. An article summary posted on ScienceDaily yesterday reports that researchers have discovered another important role for 'junk' DNA; indeed this summary reports that junk DNA plays a "central" role in the organism.

They have discovered that DNA sequences from regions of what had been viewed as the "dispensable genome" are actually performing functions that are central for the organism. They have concluded that the genes spur an almost acrobatic rearrangement of the entire genome that is necessary for the organism to grow... ...transposons appear to first influence hundreds of thousands of DNA pieces to regroup. Then, when no longer needed, the organism cleverly erases the transposases from its genetic material, paring its genome to a slim 5 percent of its original load. "The transposons actually perform a central role for the cell," said Laura Landweber, a professor of ecology and evolutionary biology at Princeton and an author of the study. "They stitch together the genes in working form."

In other words, enzymes called transposases reorganize the genome of an organism, then when no longer needed are removed from the organism. The article reports that these transposases are passed on in the form of maternal RNAs that is briefly passed to offspring, that also provide templates to facilitate genomic rearrangement.

We can add this to the growing list of functions that have been discovered for DNA once alleged to be 'junk.' There has always been evidence that non-coding DNA was not in fact 'junk'; for example: Studies indicated that long areas of non-coding DNA were constructed of palindromic sequences and that these palindromes maintained a symmetry between opposite complementary strands. Another study that employed statistical techniques co-opted from linguistics to study non-coding DNA within genomes, reported that non-coding DNA is organized into patterns that resemble patterns observed in human languages. Large portions of the genome called heterochromatin, which in the past were thought of as junk DNA, have been reported to play a role in the inactivation of genes, and suppression of their expression. Other evidence suggests that non-coding DNA plays a critical role in regulating expression of genes during development in general, which is further affirmed in the ScienceDaily summary that prompted this blog entry.

In addition, non-coding DNA has been reported to regulate the expression of specific genes that control development of the central nervous system, the reproductive tract, and photoreceptor cells present in the eye. Functional roles have even been found for pseudogenes. Prior to 2003, there were no known functions for any pseudogenes; pseudogenes were thought to be non-fuctional relics of related functional genes that are no longer translated and expressed in the cell. Researchers inserted a fruitfly gene into a pseudogene called Makorin1-p1 in mice. It was discovered that this lineage of genetically-altered mice exhibited multi-organ failure in approximately 80% of the individuals; the researchers on this project learned that this pseudogene was expressing an RNA molecule that regulated the expression of a functional Makorin1-p1 gene. Thus we can add this example to the growing list of functions for non-coding, or what has been historically - and unfortunately - termed "junk DNA". Indeed, this growing list of functions is extremely numerous and diverse, and contrary to popular opinion - and in stark contrast to the evolutionary explanation typically employed to explain the presence of "junk DNA" - more and more it appears that non-coding DNA is a dynamic and essential component of genome functionality, not a useless relic of imperfect process of evolution.