Turns out sperm don't have mitochondrial DNA

Does that matter? And how did we not know that before?

Artist’s drawing of DNA. By Brano on Unsplash

We’ve known for a long time that mitochondria have their own DNA, that probably comes from way back when mitochondria were free living bacteria¹. We’ve also known that all our mitochondrial DNA (mtDNA) comes from our mothers, not our fathers². But the details of how and why we don’t inherit mtDNA from our fathers hasn’t been clear. Sperm certainly have mitochondria, so why don’t we inherit the DNA?

A group at Thomas Jefferson University published a paper this week in Nature Genetics showing a surprisingly simple answer: sperm have mitochondria but no mtDNA!

The authors showed that as human sperm cells go through development the amount of mtDNA they have decreases, until finally when they are fully mature sperm, ready to go off into the world and have adventures, they have no mtDNA at all. 

The researchers showed a possible mechanism too. There’s a protein, TFAM, that usually gets imported into the mitochondria, and sits in the little bundles of mtDNA, working to keep the DNA intact. Without this protein, cells lose their mitochondrial DNA pretty quickly. The authors of the study found that while sperm still have this protein, it’s different.

They saw that in sperm, TFAM was a tiny bit bigger than normal, and the protein turned out to be a slightly different version that can’t get sent to the mitochondria. So all the TFAM stayed out of the mitochondria, which from the mitochondria’s point of view makes it as good as gone. Without it, mitochondria can’t hold on to their DNA and pretty soon they have none left. 

Hold on, don’t sperm need functioning mitochondria to swim fast?

But aren’t mitochondria famously “the powerhouse of the cell,” and don’t sperm need to swim like crazy? So don’t they need perfect working mitochondria? It seems like there are two answers for this. Sperm can still do glycolysis, the “fast” form of energy production that happens outside the mitochondria that your muscles do when sprinting (rather than running a marathon). “Anaerobic” respiration, just breaking down sugar. 

But more than that, the authors suggest that even though the sperm lost their mtDNA, that doesn’t mean they also lost the mitochondrial proteins that the DNA codes for. Since DNA codes for protein assembly the way an instruction manual tells you how to assemble a piece of furniture, you could imagine if you’ve already built your IKEA dresser, you can throw away the instructions and you still have your dresser. So the sperm could still have perfectly functioning mitochondria using proteins the cell made before it threw its mtDNA away. This wouldn’t last if sperm had to divide and multiply and make more mitochondria, but mature sperm are done dividing.

Didn’t anyone see this before? Did no one think to look?

There’s been this huge mystery about why we don’t inherit paternal mtDNA, and no one thought to look and see if it was even there in the first place? Are we dumb? 

There are a few answers to this! And none of them are stupidity!  

In some studies, researchers equated mitochondria with mitochondrial DNA, meaning that they saw sperm still had mitochondria and assumed that meant they came along with DNA too, since there aren’t really other human cells that have no mtDNA. 

Another explanation is that in some studies, researchers used slightly immature sperm taken out of the testes of mice to study the cells. And in these cases the cells do still have DNA, just less of it. However, one paper the ‘80s specifically studied mtDNA in mature mouse sperm, and found less DNA in mouse sperm but not zero. So there’s a possibility that human and mouse sperm development is just different enough that humans lose all mtDNA and mice lose most mtDNA. 

Similarly in mice it was shown that after fertilization, the mitochondria from the father are degraded, but the authors of the new study say that this degradation hasn’t really been seen in humans. So it’s possible that in mice, sperm have a tiny bit of mtDNA left, but that’s ok because it’ll get degraded, while in people there’s no mtDNA left in sperm so the male mitochondria don’t have to get degraded. That so much research is done on mice, not humans, could explain how this phenomenon was missed for so long. 

It has been shown in people that higher amounts of mtDNA in semen correlates with infertility, which fits with the idea that we need sperm to have no mtDNA. In these fertility studies though, people were testing whole semen samples from humans at a fertility clinic, and those samples also contain plenty of contaminating non-sperm cells picked up on the way out, which again could explain why there was always some mtDNA signal even in the perfectly healthy samples, so again the idea that sperm actually have no mtDNA at all, was missed. 

Why does this happen at all? But why not just inherit dad’s mtDNA? 

All this leads to one of the truly absurd things about life, that you could argue is the reason we are here at all and didn’t die out hundreds of millions of years ago, right after life evolved: that an organism that is old, can give rise to one that is young. 

Take people: two adults, in their thirties, for example, with all the signs of aging that go along with having lived thirty years, can produce a baby who is zero years old with no signs of aging. How do young cells come out of old people?

There are a lot of theories and hypotheses about how this happens, but one thing is certain, that new young cells need good quality organelles (the components that makes up cells), especially good mitochondria. And female egg cells, oocytes, undergo extreme quality control while they are developing to keep the mitochondria in pristine shape.

Oocytes in female bodies appear during the development of the fetus³, and barely divide at all, all the way to adulthood, and they hold on to their perfect little mitochondria, while sperm on the other hand are dividing frequently. So it makes sense to only want to inherit the mtDNA that has been handled carefully, when the future of the species depends on it. This isn’t perfect forever though, and mitochondrial quality dose slowly decline with age and has been implicated as one of many reasons women are less fertile as they get older.

Notes:

¹The paper linked here is by Lynn Margulis (at the time Lynn Sagan) it’s her first presenting the idea of endosymbiosis. She suggested that mitochondria, chloroplasts in plants, and flagella were once free living. Flagella turned out to be wrong later but the other two have turned out to be right! At the time she was harshly criticized for the suggestion, even reportedly receiving a grant review telling her that her work was so terrible it wasn't even worth trying to reapply for the grant. Joke’s on them. 

²Sometimes very very rarely, humans do inherit mtNDA from their dads, and that is generally not so great for the person it has happened to. There is at least one known case of a man who had severe “exercise intolerance”, unable to run at all, and it turned out he had a mutation in his mtDNA that he had somehow inherited from his father. 

³This does mean that the egg that became you was inside your mother already, when she was a fetus inside your grandmother!