BMC Evolutionary Biology
:125http://www.biomedcentral.com/1471-2148/8/125Page 3 of 13
(page number not for citation purposes)
ical selection coefficients
between which extinction isexpected to occur in a given interval of time [6,9]. This
critical range of selection coefficients corresponds to theclass of deleterious mutations that are sufficiently weak that they can accumulate, yet are strong enough to nega-tively impact fitness.
For the nuclear genome, the results show that
cannot survive pure selfing for extended periods of time inthe absence of mitigating forces, across most plausibleparameter combinations (Figure1). For example, consid-ering
= 0.5, a value that might closely reflect the truehaploid genomic deleterious mutation rate (see Meth-ods), we expect an extinction time of less than 10 Kyr (~6× 10
generations, assuming an average 60 day generationtime in nature) for a range of critical selection coefficients
between about 0.0003 and 0.09. Even in the absence of precise estimates of the distribution of deleterious muta-tional effects on fitness (DDME) in
, we can becertain that a substantial fraction of all deleterious muta-tions will have effects in that range [23,24]. This assump-
tion is confirmed by our point estimate of the DDME (seebelow), which suggests that
= 51% of all mutationshave effects between
= 0.0003 and 0.09. Generation timeexerts a linear effect on the expected extinction time, sothe contribution of uncertainty in this life history charac-ter does not qualitatively alter the principal conclusion(Figure1). Maximal reproductive output
enters only as its log in the computation of extinction time. Conse-quently, even large changes to
cause only minimalchanges in extinction time, rendering our results robust tothis parameter, as well. The effective population size
can have a large effect on the operation of the ratchet, but only for the minority of mutations with effects that are very close to the 'wall of background selection' and wouldbe eliminated deterministically by selection; because wesimulate the whole range of realistic
values, our resultsare robust in this regard as well. In general, the conclusionthat
cannot persist over extended periods of evolutionary time in a purely selfing state is robust touncertainty in
and other parameters.
The results for the mitochondrial genome in
areless dire (Figure2). The parameter values that are most plausible yield extinction times close to the estimated ageof common ancestry with related species (~18 Myr). Thus,the genomic decay of
mitochondria is not strongly implicated as an important factor limiting thepersistence of this species since its divergence with sister taxa. Although we know of no evidence for or against thepresence of mitochondrial recombination in
,despite examples from other nematodes [25,26], such a
phenomenon would only reduce the potential for Muller's ratchet to operate in mitochondria.
These results indicate either that a predominantly selfing mode of reproduction is a recent innovation in the
C. ele- gans
lineage or that compensatory mutation and/or regu-lar bouts of outcrossing contribute to species persistence.For the most plausible estimates of the nuclear deleteriousmutation rate we conclude that Muller's ratchet wouldhave led to extinction within thousands of years (tens or hundreds of thousands of generations). More generally,current knowledge about mutation rates and the distribu-tion of deleterious mutational effects (DDME) cannot bereconciled easily with extinction times of more than a mil-lion years in the absence of outcrossing.
Segregation in selfers
Previous work has shown that the segregation of deleteri-ous mutations that occurs during meiosis can reduce therate of mutation accumulation . The same is true for asexual species that experience mitotic recombination[28,12]. Because recombination can stop Muller's ratchet
[11,29], one might argue that segregation in selfers could
be sufficient to halt Muller's ratchet. However, existing theory shows that this would be true only if all mutationshave effects of a specific size such that their doubling willshift them into the domain of background selection andthus prevent their accumulation [10-12]. This is not likely
to stop Muller's ratchet if there is a broad, continuous dis-tribution of deleterious mutational effects, as is most compatible with our present understanding. If our analy-sis is corrected for the maximal recombinational repair that can come from free recombination within a selfer [10-12], then it still indicates that Muller's ratchet contin-
ues to operate (to apply this correction we use the haploidgenomic mutation rate of
= 0.5 instead of the dip-loid rate of
= 1 in Figure1). Thus purging of delete-rious mutations by segregation in selfers is not expected tostop Muller's ratchet here.
Our analysis of Muller's ratchet assumes pure selfing, yet population genetic studies have demonstrated that out-crossing does occur at low levels in
[13,14,30,15,31,32]. However, recent evidence of out-
breeding depression in
 and of changes inmultilocus haplotype frequencies over time in nature, in which recombinants appear to suffer a fitness dis-advantage, indicate that outcrossing and effective recom-bination are selected against, even if they occur within thesame population. In laboratory populations, males andoutcrossing are selected against, although elevated muta-tion rates and some genetic backgrounds partially miti-gate this effect [34-38]. Furthermore, females of obligate