Certain concepts simply irk me. They are often needlessly complicated and their meaning gets distorted in an attempt to make them understandable.
Take, for example, the idea of a Mitochondrial Eve.
That term came about in 1987, and because of the presence of that weighty name, Eve, it conjures up the idea of the first woman. The fact that a news item in the journal Nature describing the concept was titled “Out of the garden of Eden” certainly didn’t help.
Mitochondrial Eve is, in one respect, like the Stanley cup. The title remains the same, but to whom it is awarded changes with the circumstances.
To fully understand who Mitochondrial Eve is, we have to take a crack at this cumbersome adjective: mitochondrial. It refers to the mitochondrion (or mitochondria, in its plural form), and the mitochondrion is both mighty and strange. It contains a genome you may not be familiar with but which ties you to your mother, and her mom, and hers, all the way back to this not-so-Biblical Eve.
The story of the mitochondrion is a story of mothers, but it is also a tale of energy.
Phosphate as currency
Living things need energy to function. What is this energy? Well, it is in the food we eat, but as this food gets broken down and converted by our body’s metabolism, we end up with the true fuel of life, a molecule called adenosine triphosphate or ATP.
The key to understanding the role that ATP plays is in the word “triphosphate.” The molecule adenosine is attached to three phosphate groups, where each phosphate is an atom of phosphorus bound to four atoms of oxygen. Crucially, the movement of these phosphate groups from one molecule to another is how energy is transferred. ATP can lose a phosphate group to another molecule, and this transfer activates that molecule and starts an important cascade of events. These phosphate groups are like dollars being exchanged from one molecule to another, and most of the ATP is made by the currency mint of the cell, the mitochondrion.
Our bodies are made of organs, themselves made of tissues, which are composed of cells, and these cells can be imagined as an egg freshly cracked over a pan. The yolk is the nucleus of the cell and the white of the egg is full of activity. Some of the structures inside this white—called “cytoplasm” in cells—are mitochondria. They were discovered in 1857 by Swiss scientist Albert von Kölliker and named in 1898 by Carl Benda, a German microbiologist who coined the name from the Greek “mitos-,” meaning “thread,” and “-chondros,” meaning “granule,” because mitochondria inside of a cell tend to form long dotted chains.
We still do not know exactly how these little powerhouses evolved to be found inside of cells. The most commonly accepted hypothesis is that they were bacteria-like organisms which were swallowed up by ancestral cells nearly two billion years ago. These little bugs were able to produce energy for the larger cell, and the two found themselves in a symbiotic relationship with each other. Now, mitochondria not only produce most of the ATP our cells need, but they are also involved in other aspects of cell life and death.
Interestingly enough, mitochondria have their own DNA, and its behaviour challenges everything nonexperts think they know about the molecule of life.
The mother of all genomes
You may remember that you inherit half of your DNA from your mother and the other half from your father; that this DNA forms 23 pairs of stick-like chromosomes; and that this DNA is copied according to a very strict cell cycle. All of these facts are true, but they apply to nuclear DNA, meaning the DNA found inside the nucleus of the cell or the yolk in the egg analogy.
Outside the nucleus, in the hundreds and sometimes thousands of mitochondria a single cell contains, there is yet more DNA to be found: the mitochondrial genome. Like a teenager defying its parents, mitochondrial DNA stands in opposition to nuclear DNA. It is copied constantly, independently of the carefully choreographed cell cycle. It does not form stick-like chromosomes, but a single, circular chromosome, a ring of DNA. And importantly, it is passed down uniquely from the mother to her children regardless of their sex.
This last fact, called maternal inheritance, has been controversial in the recent past. In 2018, a team of researchers claimed to have found evidence in three unrelated families of biparental inheritance, meaning that some of the mitochondrial DNA in children came from their father as well. To rule out contamination or sample mix-up, the researchers had the tests repeated by multiple laboratories using fresh blood samples. Paternal inheritance of mitochondrial DNA has been reported in the fruit fly, mouse, and sheep, and 20 years ago, there was a published report of one man whose muscles seemingly contained mitochondrial DNA from his dad, but this 2018 paper was a real shocker. Its authors even dared to write that their results ran “counter to the central dogma of mitochondrial inheritance.”
Last year, however, a better explanation was proposed. Whenever this rare phenomenon is seen, the mitochondrial DNA is inherited in a way that recalls how a father and a mother’s nuclear DNA makes its way into their children. It would appear that the mitochondrial DNA detected in those cases of biparental inheritance does not come from the mitochondria themselves. Rather, they are bits of mitochondrial DNA that have made their way inside the nucleus of a cell and integrated themselves to the chromosomes. They are thus passengers, and they end up being inherited alongside the rest of a mother’s and a father’s nuclear chromosomes. A review article of this phenomenon points out an important lesson: the existence of these passengers does not challenge the dogma of how the mitochondrial genome is inherited from one generation to the next. Rather, a more parsimonious explanation exists. The DNA inside mitochondria in humans is indeed passed down from the mother to her children, but sometimes bits of mitochondrial DNA end up inside the nuclear genome of the father and are inherited by the children. The dogma of maternal inheritance is still valid. Puzzling findings don’t always usher in a new scientific revolution, after all.
This ring of DNA we inherit from our mother is quite tough and it comes in handy in the field of human identification. Nuclear DNA is easily destroyed after death. Enzymes grab a hold of the end of this string of DNA and chew it up like Pac-Man. Humidity and ultraviolet light also play havoc on the nuclear DNA of dead bodies. Mitochondrial DNA, however, is more resilient. Its circular shape discourages enzymes that need a clean end to start feasting, and the presence of hundreds of mitochondria in each cell, with each mitochondrion containing two to 10 copies of its DNA, means there is plenty of mitochondrial DNA to ensure its survival. This is why the identification of very old bodies exposed to the elements can be impossible with nuclear DNA, but not with mitochondrial DNA. In humans, the mitochondrial genome contains 37 genes and a stretch called the hypervariable region, which has enough variation as to constitute a fingerprint. When compared to the same region in a maternal relative, a body can thus be identified.
Variation can also occur in one of the 37 genes, and some of these mutations result in mitochondrial diseases. Many of these conditions involve the nervous system, including a type of vision loss and various muscular issues. A controversial way to prevent this from happening is the creation of a so-called “three-parent baby.” In 2016, an American fertility clinic revealed it had created a boy in this way. His mother carried a debilitating mutation in her mitochondria. Only a minority of her mitochondria had this mutation, however, making her a carrier for this disease called Leigh syndrome. But if her child were to inherit the mutation, and if the mitochondria with the mutation were to greatly outnumber the ones without it, the child would express the disease, leading to disability and a rapid progression to death.
So, the team at the fertility clinic took an egg from a healthy woman. They sequenced her mitochondrial genome to make sure it did not have any disease-causing mutation. They removed its nucleus and replaced it with the nucleus of the woman who was a carrier for Leigh syndrome. This new egg was fertilized by the father’s sperm and it was implanted in the mother’s uterus. The baby was born in April 2016. Half of its nuclear DNA comes from his dad. The other half comes from his mom. But the vast majority of his mitochondrial DNA comes from a third person, this healthy donor, thus theoretically thwarting Leigh syndrome. I say “the vast majority” because it was revealed that, somehow, some of the mutation-carrying mitochondrial DNA from the mother did make its way into the egg.
This genetic adventure raised important ethical questions, such as the long-term risks of this sort of biological manipulation and whether or not the parents were properly informed about them. But what it also shows is that DNA does not have to be destiny as our knowledge of our biology expands and our technical expertise is refined.
All of this brings us back to Mitochondrial Eve. She was not the first human woman, nor was she the only living woman of her time. She existed sometime between 100,000 and 230,000 years ago, probably in Africa. Because the mitochondrial genome is given from a mother to her children, and from those female children to their own descendants, scientists began to think about how far back they could go up this line of transmission. This line is called the matrilineage. If you close your eyes and think of every living human being alive right now, all eight billion of us, and you go up one generation to find all of our mothers, then up another generation to find all of their mothers, and up the genealogical stream for many, many generations, you will ultimately arrive at one woman. This is Mitochondrial Eve or, less succinctly, our matrilineal Most Recent Common Ancestor or MRCA.
But as certain families only produce sons, and as some generations never reproduce, certain matrilineages become extinct, which changes who Mitochondrial Eve is. Like the Stanley cup, the title is passed down as circumstances change.
I find the idea of a Mitochondrial Eve a bit niche and too easily misunderstood. Then again, mitochondria themselves and the circular DNA they contain are also a bit niche and easily misunderstood. We need them even if, like teenagers, they choose to do things their own way.
Take-home message:
- Mitochondria are tiny structures inside our cells responsible for energy production and other aspects of cell life and death
- Mitochondria contain a unique DNA molecule, distinct from our 23 pairs of chromosomes, and this DNA in humans is inherited from our mother
- Mitochondrial Eve is a title given to the most recent woman in history to whom all living human beings today can trace their maternal ancestry
