The Mother’s Curse: Insight into the Effects of Maternal Mitochondrial Inheritance

A new study pub­lished in Evol­u­tion Let­ters provides sup­port for the ‘Mother’s Curse’ hypo­thes­is in a more gen­er­al­is­able way than pre­vi­ously demon­strated. Lor­can Carne­gie, who is an author on the paper, gives us an over­view of the findings.

Mito­chon­dria are organ­elles that drive the pro­duc­tion of cel­lu­lar energy and meta­bol­ic sub­stances in many forms of life. Cru­cially, mito­chon­dri­al func­tion is depend­ent on inter­ac­tions of both the nuc­le­ar and mito­chon­dri­al genomes.

That’s all well and good, but what is the Mother’s Curse? Well, here’s a quick break-down for those of you who are unac­quain­ted with this top­ic: mito­chon­dria are not passed on to the next gen­er­a­tion by both par­ents – they exhib­it strict mater­nal inher­it­ance across most spe­cies. The ‘Mother­’s Curse’ hypo­thes­is sug­gests that, as all adapt­a­tions that are bene­fi­cial for females are not also good for males, this evol­u­tion­ary bias (or ‘sex-spe­cif­ic select­ive sieve’) enables the accu­mu­la­tion of male-harm­ful muta­tions in mito­chon­dri­al DNA (Fig. 1). Okay, so why don’t males go extinct?… Well, it is believed that nuc­le­ar alleles arise that com­pensate for male-harm­ing mito­chon­dri­al DNA muta­tions. How­ever, giv­en the dif­fer­ence in evol­u­tion rates between mito­chon­dri­al and nuc­le­ar genes (the nuc­le­ar gen­ome mutat­ing at a much slower rate) this grand res­cuing force is thought to often lag behind the effects of the Curse.

Fig­ure 1. Illus­tra­tions of ele­ments of the Mother’s Curse hypo­thes­is. A) Puri­fy­ing selec­tion (the sieve) removes only muta­tions that are bad for females, B) Sex-spe­cif­ic sieve has min­im­al impact when little dif­fer­ences in trait value between sexes, C) When trait val­ues dif­fer between sexes, the sex-spe­cif­ic sieve means male fit­ness is lowered.

There are two test­able pre­dic­tions asso­ci­ated with the pres­ence of the Curse. A first pre­dic­tion is that traits with high meta­bol­ic demands (i.e., rely a lot on mito­chon­dri­al func­tion) whose expres­sion var­ies between the sexes (i.e., dif­fer­ent selec­tion on female mito­chon­dri­al DNA than males) should be most to be affected by the Mother’s Curse. A second pre­dic­tion is that, because pop­u­la­tions should har­bour mito­chon­dri­al gen­omes com­pris­ing male-harm­ful mito­chon­dri­al muta­tion loads, we should see great­er levels of mito­chon­dri­al genet­ic vari­ance in its males than in its females. While dif­fer­ent pop­u­la­tions should evolve along their own pop­u­la­tion-spe­cif­ic tra­ject­or­ies and accu­mu­late their own dis­tinct­ive pools of male-harm­ing mito­chon­dri­al DNA muta­tions, such muta­tions can be unmasked by pla­cing the mito­chon­dri­al gen­ome along­side a for­eign nuc­le­ar genome!

So, what proof is there that the Curse truly exists? There has been anec­dot­al evid­ence for male-dele­ter­i­ous mito­chon­dri­al muta­tions in humans, mice, and fowl. Addi­tion­ally, some past exper­i­ment­al work using fruit flies (Dro­so­phila melano­gaster) provides some sup­port for the hypo­thes­is. How­ever, these past Dro­so­phila stud­ies used a very small num­ber of nuc­le­ar and mito­chon­dri­al gen­o­types. There­fore, we don’t know if the Mother’s Curse is gen­er­al­is­able across spe­cies like Dro­so­phila that have high levels of genet­ic variation! 

The solu­tion? We invest­ig­ated the pres­ence of the Mother’s Curse using a mito-nuc­le­ar genet­ic pan­el pro­duced through the pair­wise-com­bin­a­tion of nine pop­u­la­tions of Dro­so­phila melano­gaster drawn from around the world. Con­sequently, this pan­el con­tained 81 unique mito-nuc­le­ar com­bin­a­tions – very large! We then screened each gen­o­type and sex com­bin­a­tion for wing centroid size, a proxy of Dro­so­phila body size. We chose this trait because it exerts high meta­bol­ic demands and there is evid­ence of diver­gent selec­tion on the trait in the two sexes.

Fig­ure 2. (A) Levels of mito­chon­dri­al genet­ic vari­ance (CVm) are high­er in males (red) than females (blue) in 8 of 9 nuc­le­ar back­grounds stud­ied, and (B) vari­ance in wing centroid size accoun­ted for by mito­chon­dri­al DNA gen­o­types is great­er in males (red) than females (blue).

Our study’s res­ults sup­port the Mother’s Curse hypo­thes­is in two ways (but please see the pub­lic­a­tion for more details). First, males showed high­er levels of mito­chon­dri­al genet­ic vari­ance (meas­ured as a coef­fi­cient of vari­ation, or CVm) than females in eight of the nine nuc­le­ar back­grounds used in this study (Fig. 2 – A). Secondly, the vari­ance accoun­ted for by mito­chon­dri­al DNA gen­o­types in our lin­ear mod­els is great­er in males than females (Fig. 2 – B). Togeth­er, these res­ults demon­strate that the Mother’s Curse is more per­vas­ive than pre­vi­ously appre­ci­ated. The pan­el will now allow us to test fur­ther pre­dic­tions of the hypo­thes­is, such as how the degree to which the sig­na­ture of the Mother­’s Curse depends on the trait’s meta­bol­ic burden.

Lor­can Carne­gie is a PhD research­er who worked with Dr Floren­cia Camus at Uni­ver­sity Col­lege Lon­don. The ori­gin­al art­icle is freely avail­able to read and down­load from Evol­u­tion Let­ters.