Mitochondrial DNA and sperm

5 minute read

Tuesday, I referred to mtDNA and sperm evolution. The topic was covered in some detail in a 2004 review paper by Neil Gemmell and colleagues, entitled, “Mother’s curse: the effect of mtDNA on individual ?tness and population viability.”

The basic idea:

  1. Mitochondrial DNA is maternally inherited, so that the mtDNA germline leading to any male is female all the rest of the way back in time.

  2. Hence, any male’s mtDNA would have been subject to selection only for success in females, never males.

  3. But male traits depend on the adequate function of mtDNA genes, possibly differently from females.

Sperm stand out as a male-only cell type that place special requirements on mitochondrial function. The midsection of each sperm cell is composed largely of mitochondria packed together to provide energy for the flagellum. In humans, several mitochondrial disorders are known to induce infertility by means of reducing sperm motility. From the mtDNA perspective, every male is sterile. Hence, the Darwinian fitness of males is irrelevant to mtDNA genes. Such a gene, behaving selfishly as genes do, might well change in ways that would reduce males’ reproduction. This is the “mother’s curse” referred to in the literature: male-only mtDNA adaptations cannot evolve, and male-centric mtDNA functions can only be maintained by differential fitness of females who carry them.

Of course, anyone who knows much evolutionary theory probably can immediately think of some ways to evade the “curse”. The usual ways are the ones by which Darwin explained the fitness of steers and the evolution of sterile castes of insects: the behavior of sterile individuals influences the fitness of their female relatives. Michael Wade and Yaniv Brandvain (2009) pick up on this mechanism with respect to mtDNA evolution. From their abstract:

The absence of paternal transmission of such extranuclear components is thought to preclude a response to selection on their effects on male viability and fertility. We overturn this dogma by showing that two mechanisms, inbreeding and kin selection, allow mitochondria to respond to selection on both male viability and fertility. Even modest levels of inbreeding allow such a response to selection when there are direct fitness effects of mitochondria on male fertility because inbreeding associates male fertility traits with mitochondrial matrilines. Male viability effects of mitochondria are also selectable whenever there are indirect fitness effects of males on the fitness of their sisters. When either of these effects is sufficiently strong, we show that there are conditions that allow the spread of mitochondria with direct effects that are harmful to females, contrary to standard expectation.

Wade and Brandvain’s argument suggests that inbreeding may be an important mechanism underlying the maintenance of mtDNA function. Inbreeding-induced associations between mtDNA variants and the fitness of nuclear genes might amplify fitness differences between mtDNA mutations. This means that situations that reduce inbreeding might relax constraints on slightly deleterious mtDNA mutations and lead to rapid mtDNA evolution. This has some interesting implications:

  1. Geographically isolated populations may individually be inbred, but isolation between them would prevent the kind of mtDNA-nuclear associations that would constrain the accumulation of deleterious mtDNA mutations. Muller’s ratchet would proceed slowly within each population, but the deleterious changes in the mtDNA lineages represented in one population would occur outside the context of nuclear DNA evolution of the other population. At an extreme, mtDNA evolution might generate genetic incompatibilities that reduce the fitness of hybrids. This is the mechanism suggested by Burton and colleagues (2006). From their abstract:
We hypothesize that because mitochondrial genes frequently evolve more rapidly than the nuclear genes with which they interact, interpopulation hybridization might be particularly disruptive to mitochondrial function. Understanding the potential impact of intergenomic (nuclear and mitochondrial) coadaptation on the evolution of allopatric populations of the intertidal copepod Tigriopus californicus has required a broadly integrative research program; here we present the results of experiments spanning the spectrum of biological organization in order to demonstrate the consequences of molecular evolution on physiological performance and organismal fitness. We suggest that disruption of mitochondrial function, known to result in a diverse set of human diseases, may frequently underlie reduced fitness in interpopulation and interspecies hybrids in animals.

This study is part of a trend, where rapidly evolving genes are examined for evidence that they may reinforce isolation between populations, causing speciation as a side effect of rapid change. Mitochondrial DNA appears promising because it has a high mutation rate and its products interact with many hundreds of genes encoded in the nucleus.

  1. Gemmell and colleagues (2004) pointed out that one strategy by which populations might avoid the risks of deleterious mtDNA mutations in males would be for females to mate with multiple males. The higher variance in male fitness introduced by mtDNA mutations might have global effects on genetic variation within a population, by means of lowering the effective sex ratio. It also would interact with other factors influencing male reproductive variance, such as male mating competition.

To me, this suggests another pathway by which changes in mating structure might influence mtDNA evolutionary dynamics. Again, inbreeding may be necessary to select on male mtDNA, but in this instance inbreeding would increase the chance that a male’s mtDNA would match his daughters – in whom he may continue to invest. In a high-inbreeding population, the disadvantages of deleterious mtDNA mutations would be reduced so that females could be more confident in the continued fertility of a single male. In contrast, kin selection would be stronger than inbreeding, and maternal uncles’ mtDNA would always match their sisters’ nieces.

Well, that’s some thinking out loud.

  1. Gemmell and colleagues further noted that sperm competition is one very important context in which the mtDNA of males may impact fitness. Lower sperm motility may not impose a strong fitness cost on males in monogamous contexts, but would be highly detrimental if a male’s sperm had to compete directly with other mens’ sperm. In this regard, it is very interesting that our close relatives, chimpanzees, have strong sperm competition while humans do not. That may well indicate different evolutionary dynamics on our mtDNA as well as upon nuclear genes that influence testis and sperm function. Possibly, energetic constraints on early hominids may have altered selection on mtDNA and effectively precluded sperm competition. Or a loss of sperm competition may have relaxed constraints on energy metabolism. Curious.


Burton RS, Ellison CK, Harrison JS. 2006. The sorry state of F2 hybrids: Consequences of rapid mitochondrial DNA evolution in allopatric populations. Am Nat 168:S14-S24. doi:10.1086/509046

Gemmell NJ, Metcalf VJ, Allendorf FW. 2004. Mother's curse: the effect of mtDNA on individual fitness and population viability. Trends Ecol Evol 19:238-244. doi:10.1016/j.tree.2004.02.002

Wade MJ, Brandvain Y. 2009. Reversing mother's curse: selection on male mitochondrial fitness effects. Evolution 63:1084-1089. doi:10.1111/j.1558-5646.2009.00614.x