Why sons inherit their mother’s curse

By Ed Yong | May 12, 2011 4:00 pm

No expecting mother would ever wish harm to befall her children. Unfortunately, she may have no choice in the matter. Due to the rules of genetics, mums always run the risk of passing a “mother’s curse” onto their sons, but not their daughters.

The curse is an ancient one, the result of events that happened billions of years ago. At a time when all life consisted of single microscopic cells, one of these swallowed another. Normally, the engulfed cell would be digested, but not this time – this time, the two cells formed an alliance. The swallowed cell transferred many of its genes to its host, keeping only those involved in providing energy. It evolved into a mitochondrion – a tiny, efficient battery that would power its host, giving it the energy to become more complex. This alliance is the foundation of all complex life on the planet. All animals, plants, fungi and algae run on mitochondria power.

This means that all animals really have two genomes – their main nuclear one, and a far smaller secondary one in their mitochondria. The two sets of genes work together, each controlling the activity of the other. But they are inherited differently. The nuclear genome is a mash-up of genes from both parents, but the mitochondrial one only comes from mum. And this asymmetry is the reason for the mother’s curse.

Mitochondrial genes in a female animal will be passed onto the next generation, but those in a male face an evolutionary dead-end. In daughters, these genes can respond to natural selection, but they are hidden from view in sons. This doesn’t matter if the genes do the same thing in males and females, but not all genes are so equitable – some benefit one sex, while encumbering the other. If mitochondrial genes change in a way that harms females, they’ll be weeded out – after all, females are their only ticket to the next generation. But if the genes change to harm males, that’s okay – males are a dead-end.

As time passes, mitochondrial genomes should gradually build up changes that impair males. In this battle of the sexes, played out in every cell, males have a natural disadvantage. This phenomenon has many names: “selective sieve”, “male mutational load”, and “mother’s curse”. Now, Paolo Innocenti from Uppsala University and Damian Dowling from Monash University have found a real example of the curse that matches the predictions from evolutionary theory.

They manipulated fruit flies (Drosophila melanogaster) to create five strains that differed only in their mitochondrial genes, which hailed from one of five countries – Australia, Benin, USA, India and Japan. Their nuclear genomes were exactly the same. They were sterilised to free them of bacterial infection. They were raised in the same environments. They were like identical computers, with different USB sticks plugged into them.

Mitochondrial genomes can influence the nuclear ones, affecting which genes are switched on and off. If the mother’s curse is real, this influence should be far greater in male flies than in female ones. And it is. Swapping the mitochondrial genomes only affected the activity of 7 genes in female flies. In male flies, the same swaps affected 1,172 genes (around 10% of the total).

These genes included many that are switched on mainly in the testes or sperm glands, and that affect the health, fertility and success of males but not females. These differences may be harmless, but it’s unlikely since most changes in gene activity have a negative effect.

Thanks to their mitochondrial inheritance, the male flies are probably carrying a heavy extra burden that their sisters lack. One of the strains, for example, was completely sterile when it was loaded with the American mitochondrial genome, but fertile when it carried its normal one. And other scientists have found that mitochondrial genes in humans, hares and other species can play important roles in the quality of sperm and the fertility of males.

Males don’t take this burden lying down. If males start becoming weak and infertile, that’s bad news for the nuclear genome, which ought to evolve ways of counteracting the effects of the mother’s curse. These defences were beyond the scope of Innocenti and Dowling’s study, but they may lie in the one part of the genome that’s only passed down from fathers to sons – the Y chromosome.

Like the mitochondrial genome, the Y chromosome is tiny. But its small squad of genes punch above their weight, steering the activity of genes throughout the rest of the genome. In fact, changes in Y’s genes seem to have a disproportionate effect on genes that control the mitochondria. It’s possible that these small sets of genes wage a battle of the sexes that we’re only starting to understand.

Reference: Innocenti, Morrow & Dowling. 2011. Experimental Evidence Supports a Sex-Specific Selective Sieve in Mitochondrial Genome Evolution. Science http://dx.doi.org/10.1126/science.1201157

Image from Jay Reimer

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Comments (9)

  1. Great post! Given the selection pressure to escape the “mother’s curse”, is there any evidence that paternal mitochondria evolve ways to bypass the mechanisms that exclude them from the fertilised egg? I have come across reports of paternally-inherited mitochondria in the literature (see, for e.g. http://www.nejm.org/doi/full/10.1056/NEJMoa020350 and http://www.nature.com/nature/journal/v352/n6332/abs/352255a0.html ). Admittedly, these cases are rare, but it got me wondering if there was some kind of arms race going on between egg and sperm, and why the egg appears to be winning…

  2. Winston Yee

    Hi Ed, that was beautifully told, and this is coming from a member of Dowling’s lab group. I especially like your computer and USB analogy.

  3. marvin

    Very interesting.
    I’m an XXY.

  4. Strombio Lentatric

    This is a well written article.

  5. Christina

    @Claire – I would presume that a major reason the maternal mitochondria usually win is that the ova are massively larger than the sperm, and thus start out with large numbers of mitochondria, whereas the sperm has only one or two mitochondria. Thus, maternal mitochondria start out massively outnumbering paternal mitochondria.

  6. Catherine steacy

    Loading comment…

  7. Catherine steacy

    @Claire and Christina,
    the male mitochondria are not inherited because they do not enter the egg.
    The head of the sperm contains the nucleus. This is the only paart of the sperm to enter the egg.The mid piece which has the mitochondria and the tail remain outside the egg.
    So only female mitochondria are inherited.

  8. Christina

    @Catherine
    Actually, the male mitochondrion does enter the ovum, but is subsequently tagged with ubiquitin and destroyed. “[T]he mitochondria, and therefore the mitochondrial DNA, usually comes from the egg only. The sperm’s mitochondria enter the egg but do not contribute genetic information to the embryo. Instead, paternal mitochondria are marked with ubiquitin to select them for later destruction inside the embryo.” from Wikipedia. It cites a ScienceNews article, but that article is subscription-only. I’ve read this in other books on genetics as well.

  9. I’ve got your male mutational load right here.
    (sorry… =P )

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