Certain concepts just irritate me: they are often unnecessarily complicated and their meaning distorted in an attempt to make them easy to understand.
For example, consider the idea of Mitochondrial Eve.
The term appeared in 1987 and recalls the first woman with its weighty name, Eve. Nature It certainly didn’t help that the title describing this concept was “Outside the Garden of Eden.”
The Mitochondrial Eve is like the Stanley Cup in some ways: the title remains the same, but who is awarded it changes depending on the circumstances.
To fully understand who Mitochondrial Eve is, we need to consider that tricky adjective: mitochondrial. It refers to mitochondria (plural: mitochondria), which are as strange as they are powerful. They contain a genome that is not very familiar to us, but that connects you to your mother, and her mother’s mother, and her mother’s mother, all the way back to the little-known Biblical Eve.
The story of mitochondria is both a story of mothers and a story of energy.
Phosphate as currency
Living organisms need energy to function. What is this energy? It is found in the food we eat, which is broken down and converted by the body’s metabolism into a molecule called adenosine triphosphate (ATP), the true fuel of life.
The key to understanding what role ATP plays is in the word “triphosphate.” An adenosine molecule is bound to three phosphate groups, each phosphate being a phosphorus atom bound to four oxygen atoms. Importantly, these phosphate groups are transferred from molecule to molecule, transferring energy. ATP can pass on a phosphate group to another molecule, activating that molecule and setting in motion a vital chain of events. These phosphate groups are like dollars exchanged between molecules, and most ATP is produced by mitochondria, the currency offices of the cell.
Our bodies are made of organs, which are themselves made of tissues, which are made up of cells. Imagine these cells as a fresh egg cracked in a frying pan. The yolk is the nucleus of the cell, and the white is the active part. Some of the structures inside this white, called the “cytoplasm” of the cell, are mitochondria. Mitochondria were discovered in 1857 by Swiss scientist Albert von Kölliker, and named in 1898 by German microbiologist Karl Benda. Benda coined the name by combining the Greek words “mitos-” meaning “thread” and “-chondros” meaning “granule,” because mitochondria tend to form long, punctate chains in cells.
We still don’t know exactly how these tiny powerhouses emerged inside our cells. The most commonly accepted hypothesis is that they were bacteria-like organisms that were engulfed by ancestral cells about 2 billion years ago. These tiny worms were able to provide energy to larger cells, and the two lived in a symbiotic relationship. Today, mitochondria not only generate most of the ATP our cells need, but they are also involved in other aspects of cell life and death.
Interestingly, mitochondria have their own DNA, and their behavior calls into question everything non-experts think they know about the molecules of life.
The mother of all genomes
You may remember that half of your DNA comes from your mother and the other half from your father, that this DNA forms 23 pairs of rod-shaped chromosomes, and that this DNA is replicated according to a very strict cell cycle. All of these facts are true, but Nuclear By DNA, we mean the DNA found in the nucleus of a cell or in the yolk of an egg.
Outside the nucleus, inside the hundreds, sometimes thousands, of mitochondria that each cell contains, there is more DNA: the mitochondrial genome. Like a rebellious teenager, mitochondrial DNA opposes nuclear DNA. It is constantly copied, independent of the carefully orchestrated cell cycle. It forms a single circular chromosome, or ring of DNA, rather than a rod-shaped chromosome. And crucially, it is passed uniquely from mother to child, regardless of gender.
This last fact, called maternal inheritance, has been controversial in recent years. In 2018, a research team claimed to have found evidence of parental inheritance in three unrelated families. This means that some of the child’s mitochondrial DNA is also inherited from the father. To rule out contamination or sample mix-up, the researchers repeated the tests in multiple laboratories using fresh blood samples. Paternal inheritance of mitochondrial DNA has been reported in fruit flies, mice, and sheep, and 20 years ago, a man was reported to have a muscle that seemed to contain his father’s mitochondrial DNA, but this 2018 paper was truly shocking. The authors even wrote that their results “contradict the central dogma of mitochondrial inheritance.”
But last year, a better explanation was proposed. In this rare phenomenon, mitochondrial DNA is passed on in a way that is reminiscent of the father’s and mother’s nuclear DNA being passed on to children. The mitochondrial DNA detected in these cases that is passed on from both parents does not seem to come from the mitochondria themselves. Rather, they are pieces of mitochondrial DNA that have made their way into the nucleus of the cell and integrated into the chromosomes. They are therefore passengers, passed on together with the rest of the nuclear chromosomes of the mother and father. A review article on the phenomenon points out an important lesson. The existence of these passengers does not challenge the dogma of how the mitochondrial genome is passed on from one generation to the next. Rather, a more succinct explanation exists. While DNA in human mitochondria is indeed passed on from mother to child, sometimes a piece of mitochondrial DNA can get inside the father’s nuclear genome and be passed on to the child. The dogma of maternal inheritance still holds good. After all, puzzling discoveries do not necessarily lead to new scientific revolutions.
This ring of DNA we inherit from our mothers is very tough, which is why it is so valuable in the field of human identification. Nuclear DNA is easily destroyed after death. Enzymes grab the ends of this strand of DNA and chew it up like Pac-Man. Moisture and UV rays also do a lot of damage to nuclear DNA in corpses. But mitochondrial DNA is more durable. Its circular shape prevents the enzymes that need clean ends from getting started. And because each cell has hundreds of mitochondria, each containing 2-10 copies of DNA, there is plenty of mitochondrial DNA to survive. This makes it impossible to identify very old, weathered bodies with nuclear DNA, but possible with mitochondrial DNA. The human mitochondrial genome contains 37 genes and regions called hypervariable regions that have enough variation to form a fingerprint. By comparing it to the same parts of maternal relatives, the body can be identified.
Mutations can also occur in one of 37 genes, and some of these mutations cause mitochondrial diseases. Many of these conditions are related to the nervous system, such as some kind of vision loss or various muscle problems. A controversial way to prevent this is the creation of so-called “three-parent babies”. In 2016, a US fertility clinic revealed that they had produced a boy using this method. His mother had a debilitating mutation in her mitochondria. However, only a small proportion of her mitochondria had this mutation, making her a carrier of the disease, called Leigh syndrome. However, if her child inherits the mutation and the number of mitochondria with the mutation significantly exceeds the number of mitochondria without the mutation, the child will manifest the disease, causing disability and rapidly leading to death.
So the fertility clinic team took eggs from healthy women and sequenced their mitochondrial genomes to make sure they didn’t have any disease-causing mutations. They then removed the egg’s nucleus and replaced it with one from a woman who was a carrier of Leigh syndrome. This new egg was fertilized by the father’s sperm and implanted in the mother’s uterus. The baby was born in April 2016. Half of the baby’s nuclear DNA came from the father, and half from the mother. But the majority of the baby’s mitochondrial DNA came from this third, healthy donor, theoretically preventing Leigh syndrome. I say “most” because it turned out that, somehow, some of the mitochondrial DNA carrying the maternal mutation made its way into the egg.
This genetic adventure has raised important ethical questions, including the long-term risks of this kind of biological manipulation and whether the parents were properly informed about it. But it also shows that as our knowledge of biology expands and our technological expertise becomes more sophisticated, DNA doesn’t have to be our destiny.
All of this brings us back to Mitochondrial Eve. She was not the first human woman, nor was she the only woman alive at that time. She was probably present in Africa sometime between 100,000 and 230,000 years ago. Because the mitochondrial genome is passed from mother to child and from the child to their descendants, scientists began to wonder how far back this line of transmission could be traced. This lineage is called the matrilineal. Close your eyes and think about every human alive today, all 8 billion of us. Then go back one generation to find all our mothers, go back another generation to find their mothers, and so on up the lineage, until you finally arrive at one woman. This is Mitochondrial Eve, or more simply, our Maternal Recent Common Ancestor (MRCA).
But as some families only produce sons, and some generations produce no offspring, some matrilineages go extinct, and the identity of Mitochondrial Eve changes. Like the Stanley Cup, the title is passed down according to changing circumstances.
I think the idea of Mitochondrial Eve is a bit niche and misunderstood, and so are mitochondria themselves and the circular DNA they contain, but 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 that are responsible for energy production and other aspects of cell life and death.
– Mitochondria contain their own DNA molecules that are separate from the 23 pairs of human chromosomes, and this DNA is inherited from the mother.
– Mitochondrial Eve is the title given to the most recent woman in history to whom all humans alive today can trace their maternal ancestry.
