Mitochondrial DNA- A Magical Mystery Tour
There are always certain prerequisites in every field of study necessary for further understanding of the field. These initial endeavors are often viewed as boring and may turn beginners off to the field of study. Learning the typical components of a generalized cell is probably one of those areas in biology that have people running for the hills. But wait- intrigue is upon us.
Mitochondria are a major organelle of a typical cell, one of the ones you most definitely learned about in an introduction to biology course. It is known as the ‘powerhouse of the cell’ because it is the major energy production site for the cell. Cellular respiration is the overall process of converting food molecules into energy, the mitochondria is the site of the second and third steps of this complex three-step process. Oxidative phosphorylation via the Electron Transport Chain (ETC) is the major ATP producer of the cell. No doubt in a biology course this lead to a rather involved look at the ETC, all of the various oxidation-reduction reactions occurring within the mitochondria to ultimately produce ATP, the major energy currency of the cell. Let’s skip all of the convoluted reactions and have the summary suffice.
Here’s where this organelle gets interesting- mitochondria have their own genome, as discovered in the 1960s by Margit M. K. Nass and Sylvan Nass and confirmed by Ellen Haslbrunner, Hans Tuppy, and Gottfried Schatz. This mitochondrial DNA (mtDNA) remains separate from the bodies’ genome, referred to as the nuclear DNA since it resides in the nucleus of the cell. The mitochondrial genome has about 16,500 base pairs and codes for 37 genes, 13 of which are involved in the process of oxidative phosphorylation and the others for transfer RNA and ribosomal RNA. mtDNA is much smaller than the nuclear genome, and it also is circular while the nuclear genome is linear. Mitochondrial DNA differs from nuclear DNA in a number of other ways as well; it has a higher rate of mutation and it is haploid. It is haploid due to the fact that it is only maternally inherited, a point to get into later. Nuclear DNA is diploid (2N, where N is the number of chromosomes) due to inheritance from both the mother and father. Nuclear DNA boasts a better repair system for DNA damage than mtDNA, which goes along with the larger size of the nuclear genome, more coding for more proteins including an extensive repair system. Take into consideration mitochondria’s main function, the electron transport chain generates reactive oxygen species (ROS) as a by-product of the energy producing system and these can damage DNA. This damage is compounded with the fact that mtDNA repair systems are not as advanced as nuclear DNA systems and the damage from ROS is not always repaired.
Mitochondrial Genome vs. Nuclear Genome
3 billion base pairs
16,500 base pairs
Number of Genes
One of the reasons why mtDNA is thought to hold answers is it appears to have been its own self-reliant organism at one time. The theory: mitochondria started as simpler organisms which, at some point in evolution, joined up with evolving multi-cellular organisms. If that is the case, having its own DNA will certainly come in handy for tracing purposes. The DNA sequence can be used to trace how far back in time the organism was on its own and when it joined up with its host. This idea summarized above describes the endosymbiotic theory which proposed the idea that certain cellular organelles were able to survive being taken up, the process called endocytosis, by a higher level organism and formed a symbiotic relationship with the host. The organelle in question would have been its own free-living bacteria and presented the host with new and advantageous capabilities. Likewise the host cell would provide a better chance at survival for the engulfed bacteria.
Let’s travel back in time and get all caught up- first we have the discovery of mitochondria as a critical cell organelle in the late 1800s. Then in the 1920s Wallin proposed the idea that mitochondria and bacteria have an awful lot in common, staining characteristics along with general side by side comparison of components. Sounds pretty primitive but remember this is the 1920s and investigational tools were lacking. It wasn’t until the 1960s when, as mentioned above, mitochondrial DNA was discovered allowing scientists to go back and re-evaluate Wallin’s ideas. Lynn Margulis did just that using a very important and unique characteristic of mitochondria to further propel this idea. Mitochondria are not created from scratch, a fancy term for this is de novo synthesis, like other organelles but instead divide. So now we have an organelle in a cell that contains its own DNA and replicates to create new copies. What does all of this sound like? Well, to scientists it sounded like the mitochondria were at some point self-sufficient individuals, and thus organisms in-and-of themselves. Although the basic idea had been around since the 20s, Margulis is the one who fought for the theory throughout her lifetime of scientific work. The endosymbiotic theory, in summary, states the mitochondria in animal cells and plastids (the most common example chloroplast in higher plants) in plant cells were once individual organisms, bacteria, which along the way were taken up by eukaryotic cell types. It makes sense right?
Well, it is important to remember the endosymbiotic theory is just that, a theory. It’s a good one and it makes sense but it is not totally proven yet. In a way it seems advances in scientific techniques have created more questions under the umbrella of this theory instead of just simply proving it. Now researchers are finding differences between various organisms’ mtDNA genome and this is adding a lot more work that needs to be done to completely prove a theory of this magnitude. Overall, the endosymbiotic theory is commonly accepted as a truth since there is enough evidence on its side.
Another intriguing thing about mitochondrial DNA is it is almost solely maternally inherited. Sperm cells contain the majority of their mitochondria in the tail, recall mitochondria are the energy producer of the cell and sperm cells need energy to swim. Sometimes the tail of the sperm doesn’t make it to fertilization and thus neither does the male’s contribution of mtDNA. When the male mitochondria do enter the egg cell, the oocyte, it is tagged for destruction. The reason for this is speculated to be due to the damage the mitochondrial DNA of the male receives during spermatogenesis. As mentioned earlier, mtDNA is susceptible to ROS damage and it does not have the proper repair mechanisms to undo this type of damage. The idea is since the male mtDNA is damaged it is tagged for destruction. This leaves the maternal mtDNA, in most circumstances, as the only mtDNA to be passed along to offspring.
Mitochondrial DNA provides a good alternative to nuclear DNA for tracing family relation for a number of reasons- including the just mentioned maternal inheritance. Nuclear DNA is from both parents and undergoes recombination, which further mixes it up making it more difficult to trace it back. Since mtDNA is, in most cases, exclusively from the mother there is no change from mother to offspring. There is more of it (many mitochondria in a given cell and a high copy number of the DNA itself), so trying to identify old remains is easier with mtDNA since the odds are better for extracting an intact sample. Also a higher rate of mtDNA mutation can come in handy with relatedness. A particularly famous case of using mtDNA came in identifying the remains of Jesse James, the outlaw notorious in the mid to late 1800s for robbery of trains and banks alike. His death was questioned partly because he was supposedly living under another name, Thomas Howard, when a fellow gang member claims he went to his house and killed him. Mitochondrial DNA analysis was run on the remains of the assumed James along with two living family members at the time of this study (published in 2000). This mtDNA analysis and comparison, along with other techniques, confirmed the remains were in fact the infamous Jesse James.
Learning about the various cell organelles in school can seem a little dull, a boring prerequisite to get through early on in the course. But mitochondria are anything but dull. The discovery that this organelle contains its own DNA has opened up extensive fields of study in both evolution and inheritance. Questions have arisen about the origin of life, the retention of certain genes in the mitochondria while others have been transferred to the nuclear genome, and the reasons behind mostly exclusive maternal inheritance of mitochondrial DNA. Answers have been found in solving mysteries of remains and adding serious weight to the endosymbiotic theory. Using mtDNA to accurately identify remains has been used in several news-grabbing headlines, notorious figures like Jesse James and more recently Saddam Hussein. Many times in science, getting through the tricky concepts and complex processes leads to the ultimate payoff for us curious types- many questions answered but still more mysteries yet to be solved.
Sources/Additional Reading available upon request.