How sperm succeed: widespread selfish genes

Sperm are supposed to all act the same, with a few genes as exceptions. Turns out it's more than just a few.....
15 January 2021

Interview with 

Robin Friedman, Ohana Biosciences

SPERM_AND_EGG

Sperm surrounding an egg cell.

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Each human sperm cell has a very random combination of DNA, taken from each of the two copies of each chromosome the person carries. Genetics orthodoxy would say that it’s therefore random which genes make it into the baby, with a few exceptions: genes that make the sperm themselves quicker and better. But scientists from Ohana Biosciences in the USA have recently discovered that this far more than a few exceptions - and the results reveal a deep conflict going on inside our own bodies. Phil Sansom spoke to author Robin Friedman...

Robin - Genes come in two copies, one from your mother and one from your father; we call those alleles. And each sperm has one of those copies of every gene. It's random chance that determines which of those two alleles gets passed on to my offspring, right? So I have a 50% chance of passing on my father's version of a gene, and a 50% chance of passing on my mother's version of a gene. But if you think about the sperm, it requires those sperm to be functionally equivalent, regardless of what genes they have; they have to swim the same, they have to fertilise the egg the same. And what we've found in this work is a mechanism by which sperm are not all created equal, and by which the genetics can actually have an effect on their function, and thereby the probability that they're going to pass that gene onto the next generation.

Phil - These are genes then that are actually good for one sperm over another?

Robin - That's right, yeah. So it can lead to sperm competition, where the sperm that are more fit might have better genetics that underlie that ability.

Phil - Is that surprising?

Robin - Yes! It's been known for a long time that there are very rare exceptions to this rule, discovered by Mendel, that you pass on genes at a 50:50 ratio to the offspring; but those exceptions are thought to be extremely rare. There are only a tiny handful that have been discovered in mammals. And in this study we used single cell RNA sequencing to look at individual spermatids - that's developing sperm in the testis - in a variety of mammalian species, to find that there are far more of these differences than we expected between sperm that could lead to this sperm competition.

Phil - How many more?

Robin - There are thousands of genes that fall into this category. It's about a third to a half of genes that are expressed in the testis. We call these genes 'genoinformative markers', or GIMs for short.

Phil - Thousands is a heck of a lot more than the few exceptions that you talked about. How are these genes getting away with favouring only one sperm, when you've just told me that actually sperm normally have got to be functionally the same - they do the same things?

Robin - First you have to understand that although sperm have only one copy of each gene, when they're developing they're actually connected by bridges, so the actual cells are sharing their contents back and forth. Now what we've found is that this class of genes - that we call GIMs - actually is not completely shared; they're not going across these bridges completely. And so that's the mechanism by which these sperm start to get functionally different.

Phil - These genes are basically sitting in their sperm and they're going, "I don't want to go to the other sperm . I don't want to send my products everywhere else. I'm happy here. Stop making me share."

Robin - Yeah, that's exactly right.

Phil - What physically are they then doing to make the sperm any better?

Robin - So we haven't actually been looking at individual sperm and studying their function. Instead we've been looking at the evolutionary traces of what these GIMs are doing over the long haul. And what we can see is that it causes an evolutionary conflict, where sperm are optimising their function, and the genes might be selfish genetic elements, because their function in the rest of your body might not be the same as the function in sperm.

Phil - Right, they're selfish in the sense that they want to get ahead in the place they are right now - AKA the sperm - no matter what bad thing it might do for you when you're grown up.

Robin - That's right, yeah. And one way that we can find evidence for this is that evolution will want to avoid these selfish elements being in conflict with the function of these genes in a human. These genes will tend to evolve to become more sperm specific over time, and you will get things like gene duplication, where a gene becomes sperm specific, and another copy of it becomes expressed in the rest of the organism. And we think this is a big reason why there are so many genes that are specific to the testis compared to other tissues, which has been a mystery for a long time.

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