If a population is infected by one or more symbionts, then patterns of mitochondrial polymorphism will be altered by natural selection acting on those symbionts. Depending on the recency of invasion and the number of symbionts present, they may either reduce or increase diversity. There can also be an alteration in the frequency distribution of haplotypes within the population (). Unfortunately, it is these parameters that are used to infer the historical demography of populations and it is difficult to distinguish demographic from symbiont-induced effects.
The initial selective sweep that occurs as the symbiont invades, and subsequent sweeps of advantageous symbiont mutations, will reduce mtDNA diversity and skew the frequency distribution of alleles towards rare variants (Maynard-Smith & Haigh 1974
; Tajima 1989b
). These are similar patterns to those produced by population bottlenecks and expansions, and a selective sweep could thus easily be mistaken for these demographic processes (Tajima 1989a
). Therefore, low mtDNA diversity alone should not be taken as evidence for a bottleneck or founder event, although this may sometimes be the case (see Rokas et al. (2001)
for a genuine example). Instead, it is likely that many cases of low mtDNA variation are not caused by demographic events but selective sweeps of symbionts running through the population.
This is supported by the observation that parasitic symbionts are commonly associated with low mitochondrial diversity (seven cases in ). In at least two of these species, it has been shown that this has been caused by a selective sweep rather than a population bottleneck (Ballard & Kreitman 1994
; Ballard 2000a
; Jiggins 2003
). These studies used an HKA test (Hudson et al. 1987
) to show that the genetic diversity of mitochondrial genes was significantly less than their nuclear counterparts. This suggests that the low mtDNA diversity is caused by the symbiont, as demographic processes would have reduced the diversity of the entire genome.
These mitochondrial selective sweeps could result from selection on any maternally transmitted element, including the mitochondria themselves, symbionts or, in female heterogametic hosts, the W sex chromosome. Confirmation that selection is acting on the symbiont has come from comparisons of infected and uninfected hosts from the same population, from different populations or from different species. For example, uninfected Acraea encedon
butterflies have more diverse mitochondria than Wolbachia
infected individuals from the same population (Jiggins 2003
). In a study that compared different populations of D. simulans
, an uninfected population in East Africa was found to have greater mtDNA diversity than infected populations from elsewhere (Dean et al. 2003
). Finally, Wolbachia
-infected species have been found to harbour lower levels of mtDNA diversity than closely related uninfected species (Shoemaker et al. 1999
The effect of a selective sweep on mtDNA diversity will in part depend on the time that has elapsed since it occurred, with diversity gradually increasing after a selective sweep. Therefore, these effects may be most important for parasitic symbionts, as these tend to have short-lived associations with their hosts and frequently transmit to new host species (Werren et al. 1995
If a symbiont is imperfectly transmitted between generations, then any uninfected offspring produced by infected females will carry the mitochondrial haplotype associated with the infection. Because this process is unidirectional, the original mtDNA lineages in the uninfected hosts will ultimately be lost and replaced by the mtDNA type associated with the symbiont (Turelli et al. 1992
; Johnstone & Hurst 1996
). Therefore, the selective sweep may affect uninfected, as well as infected, hosts. However, whether this occurs will depend on the time that has elapsed since the symbiont invaded and the transmission rate of the symbiont from mother to offspring (Turelli et al. 1992
; Johnstone & Hurst 1996
). This is illustrated by two closely related species of butterfly, Acraea encedana
and A. encedon
, which are infected by male-killing Wolbachia
. The infection in the former species is older and has a lower transmission rate than the latter species. As expected, the selective sweep has eliminated mtDNA variation from both infected and uninfected individuals of A. encedana
but has only affected infected females of A. encedon
So far we have only considered the simplest scenario in which a single symbiont invades an uninfected population. It is also common to find multiple strains of cytoplasmic incompatibility inducing Wolbachia
co-infecting the same individuals. In this situation, the effects on mtDNA will be qualitatively similar to a single infection. However, some symbionts are polymorphic, with different infections occurring in different individuals but never co-infecting the same host. In the five cases where this has been examined, the different symbionts are associated with different mtDNA sequences (James & Ballard 2000
; Schulenburg et al. 2002
; Baudry et al. 2003
; Jiggins 2003
). Therefore, although a selective sweep may reduce the diversity of mtDNA associated with any one symbiont, high levels of diversity may be maintained within the population as a whole across different infection classes and the diversity of a population will depend on the number of symbionts it harbours. This can result in a mitochondrial genealogy with deep internal branches and short terminal branches, which could easily be mistaken as evidence for population structure and admixture (F. Jiggins, unpublished results).
Once a symbiont has invaded and reached equilibrium, the associated mtDNA will gradually accumulate mutations, and patterns of polymorphism may eventually resemble those expected under neutrality (e.g. Keller et al. 2004
; Marshall 2004
). However, it is notable that there are only two case studies from 19 in which mtDNA diversity in symbiont-infected species was compatible with that expected in the comparable uninfected species. There are several reasons why diversity may not return to ‘normal’. The first is that mutations may occur that increase the symbiont's fitness and are fixed by positive selection, resulting in recurrent selective sweeps through the population. Evidence for this process comes from a strong positive selection found to act on certain symbiont genes (Jiggins et al. 2002
), which contrasts with mitochondrial genes that tend to be under a purifying selection. This process may be particularly important in parasitic interactions, where host–parasite coevolution can result in strong directional selection (Jiggins et al. 2002
). However, if an advantageous mutation occurs in a beneficial symbiont, it may also cause a selective sweep of mtDNA. That this may be a regular occurrence is suggested by the observation that genome reduction of beneficial symbionts is common during the early stages of symbiosis and must be associated with selective sweeps within the population.
The second reason that diversity may fail to return to pre-infection levels is that the effective population size of mtDNA is lower after infection. There are two causes of this. First, in cases where there is inefficient transmission, only mutations in infected individuals can spread. Thus, the effective population size diminishes to that of the number of infected females (Johnstone & Hurst 1996
). In cases of low prevalence infection, as found for many male-killers, significant reduction in diversity at equilibrium is therefore expected. The reduced variation in mtDNA relative to nuclear DNA in D. innubila
, compared with the same metric in D. falleni
, an uninfected sibling species, can be explained by a model based on the reduced effective population size of mtDNA associated with a prevalence of infection in this species of 35% (Dyer & Jaenike 2004
). The second cause of diminished effective population size is greater efficacy of background selection in the presence of a symbiont. Background selection can be understood as a reduction in the mitochondrial effective population size to the proportion of cytoplasms free from deleterious mutations (Charlesworth et al. 1993
). Its impact on mtDNA diversity will be greatest when the deleterious mutation rate is highest. Considering the relative mutation rates and genome sizes of symbionts and mtDNA (Tamura 1992
; Ochman et al. 1999
; Sun et al. 2001
; Wernegreen 2002
), the total cytoplasmic mutation rate will be increased roughly tenfold in symbiont-infected hosts. However, it is unclear whether mitochondrial and symbiont mutations will have similar effects on fitness, nor whether mtDNA lies in a region of parameter space where background selection is important.