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CUMULATIVE EFFECTS OF SPONTANEOUS MUTATION ON VIABILITY IN TWO STRAINS OF
RHABDITID NEMATODES
D. Blanton, V. Chik, D. St. Clair, C. Baer
University of Florida
Department of Zoology
MATERIALS AND METHODS
ABSTRACT
Classical values for the genomic mutation rate for fitness (U) have been established in
Drosophila melanogaster by Mukai et al. (Mukai, 1972). Recent studies, both in Drosophila
RESULTS
Procedure-
Change in the Mean - Mean egg-to-adult viability declined significantly (F1,112=19.33, P<0.0001)
Four strains of rhabditid nematodes were used, two strains of Caenorhabditis elegans (N2 and PB306) and two strains of C. briggsae (HK104 and PB800).
over 250 generations of mutation in both strains. On average, HK104 declined faster than N2 (ΔMHK
Two treatments were employed: the unmutated ancestor (control) and the descendent (MA) lines that had accumulated mutations for ~250 generations. Data
(Fry, 2004) and Caenorhabditis elegans (Keightley & Caballero 1997; Vassilieva and Lynch
= 0.011%/gen; ΔMN2 = 0.0057%/gen), consistent with the results for lifetime fecundity and total
on fecundity were taken from Baer et al. (2005). The viability assay was conducted in four blocks. Each block consisted of 10 (different) MA lines and five
1999) suggest rates of mutation significantly lower than the classical values. To establish a
fitness, but the rate of decline did not differ significantly between strains (F1,112 = 0.81, P<0.37).
control lines. On day one of each block, all lines were replicated five times by the transfer of a single worm to an individual plate. On day five, one gravid
more direct comparison to the work done in Drosophila, we have assayed egg to adult viability
Change in the Variance - As expected, the among-line (genetic) component of variance increased
adult was picked from each plate (75 total plates per strain), and transferred to a new plate. On day nine, ten eggs were picked from each plate and transferred
in C. elegans (strain N2) and Caenorhabditis briggsae (Strain HK104).
over 250 generations of MA. The scaled variance, CVM, was almost identical between the two
to a new plate. Subsequently, the fraction of the original ten eggs hatched for each plate was determined.
We found that the point estimate of U for viability was five times higher in HK104 than in N2
strains (CVM,N2 = 0.92, CVM,HK = 0.97).
Data Analysis -
(0.025/generation vs. 0.005 per generation). For both strains, mean egg-to-adult viability
Change in the Mean - The change in mean viability between control (Generation 0) and MA (generation 250) worms is reported as % change per generation,
Genetic correlation between Viability and Fecundity - The two strains exhibit qualitatively different
declined significantly over 250 generations of MA. N2 showed a positive correlation between
ΔM. Differences between groups (Control/MA, strain, block, and line) were assessed by Generalized Linear Mixed Model with binomially-distributed data..
genetic correlations between survivorship and fecundity; rN2= 0.65, close to the expected value of
viability and fecundity (r=0.65), while HK104 showed no significant correlation between
Change in the Variance - In an MA experiment, the among-line component of variance (Vb) is the genetic variance. Since all lines are initially genetically
0.8 if mutational effects are perfectly correlated. Conversely, rHK = -0.25, which certainly does not
viability and fecundity, suggesting that the relationship between these two indicators of fitness
identical, Vb = 0 in generation zero (= control), and increases over time as mutations accumulate. We report the mutational coefficient of variation (CVM) in
differ significantly from zero.
viability for each strain, where CVM = 100[Vb/2t]1/2/MMA where Vb is the among-line component of variance, t is the number of generations of MA (= 250),
is qualitatively different between species.
and MMA is the mean survivorship of the MA lines, estimated by least-squares from the full model.
INTRODUCTION
Genomic mutation rate, U - The Bateman-Mukai estimate of mutation rate for viability in HK104 is
five-fold higher than that for N2 (UMIN,HK = 0.026/gen; UMIN,N2 = 0.005/gen).
Genetic Covariance Between Viability and Fecundity - The genetic covariance between viability and fecundity is the among-(MA) line component of
covariance between the two traits. Fecundity data are taken from worms assayed after 200 generations of MA (Baer et al. 2005). Lines measured at Gen 200
Mutation has been examined in terms of its role in introducing new genetic variation
and 250 share 80% of their history in common; thus if the true correlation of mutational effects is 1 the expected observed correlation is 0.8.
(Charlesworth and Hughes, 2000) and its impact on fitness as observed via life history traits
DISCUSSION
Genomic Mutation Rate, U - The genomic mutation rate, U, for viability was estimated by the Bateman-Mukai method (Lynch and Walsh 1998), where the
(Mukai, 1964). Mukai et al. (1972) found that egg-to-adult viability in Drosophila melanogaster
downwardly-biased estimator of U, UMIN = [2(Rm)2] / Vb, where Rm is the difference between the control and MA means, divided by the number of
declined at the rate of ~1% per genome per generation, and that there were approximately 0.6
generation of MA and Vb is the among-line component of variance, divided by the number of generations of MA.
Discussion
Previous experiments showed that the cumulative deleterious effects of new mutations vary between
mutations per genome per generation for fitness (i.e., U = 0.6). However, several recent
strains and species of Rhabditid nematodes. The most pronounced difference was between the N2
Drosophila studies have reported mutation rates much lower than the "classical" values of Mukai
Caenorhabditis elegans (Keightley & Caballero 1997; Vassilieva and Lynch 1999) consistently
12
10
8
6
N2 (C.
elegans)
4
HK104 trendline
y = 0.0038x
4.1488
Linear+(N2
2
R = 0.0069
(C.
2
0
estimate U for fitness on the order of one to two orders of magnitude less than the classical
0
estimates. There are two possible explanations for the variability among studies: either U for
100
150
Productivity
200
250
Survivorship vs. Productivity for two strains of rhabditid
nematode
fitness is really much smaller than reported by Mukai and his co-workers, or there is considerable
genetic variation in mutational properties.
50
Figure 1
0.2
elegans, C. briggsae, and Oscheius myriophila. The overall results were qualitatively consistent
0.0
with the previous estimates from C. elegans, but C. briggsae declined in lifetime fecundity and
0
Here we report results of an experiment designed to yield more accurate estimates of egg-to-adult
viability of a subset of the Caenorhabditis mutation accumulation (“MA”) lines. There are two
reasons that viability per se is of interest; first, to allow a more direct comparison to the classical
Drosophila studies, and second, to estimate the genetic correlation between mutations that affect
W
total fitness (fecundity weighted by survivorship) about twice as fast as the other species.
100
200
0
100
-0.25
-0.5
200
N2 (C. elegans)
we cannot rule out identical rates of decay. Interestingly, the genetic correlation between viability and
HK104 (C.
briggsae)
fecundity differs qualitatively between the two strains. Possible explanations for the difference
Generation
Decline in survivorship over 250 generations of mutation
accumulation for two strains of rhabditid nematode.
Figure 2
include different mutational spectra (e.g., HK104 may have an active transposable element) and/or
different degrees of genetic robustness.
LITERATURE CITED
Baer, CF, Shaw, F, Steding, C, Baurngartner, M, Hawkins, A, Houppert, A, Mason, N, Reed, M, Sinnonelic,
K, Woodard, W, Lynch, M. 2005. Comparative evolutionary genetics of spontaneous mutations affecting
fitness in rhabditid nematodes. Proceedings of the National Academic of the Sciences. 102: 5785-5790.
Charlesworth, B, and Hughes, KA. 2000. The maintenence of genetic variation in life-history traits. Book:
Evolutionary Genetics: From Molecules to Morphology. 369–392.
-0.2
Fry, JD. 2004. On the rate and linearity of viability declines in Drosophila mutation-accumulation
experiments: Genomic mutation rates and synergistic epistasis revisited. Genetics 166: 797-806.
-0.4
Jones, AG, Arnold, SJ, Borger, R. 2003. Stability of the G-matrix in a population experiencing pleiotropic
mutation, stabilizing selection, and genetic drift. Evolution. 57: 1747-1760.
-0.6
Keightley, PD and Caballero, A. 1997. Genomic mutation rates for lifetime reproductive output and lifespan
in Caenorhabditis elegans. Proceedings of the National Academy of the Sciences 94: 3823-3827.
-0.8
N2 (elegans)
PB306 (elegans)
HK (briggsae)
PB800 (briggsae)
-1.0
Generation
viability and those that affect fecundity. Mutational correlations are largely due to pleiotropy and
Linear (N2
(C.
elegans))
average at twice the rate of N2. Egg-to-adult viability shows essentially the same pattern, although
0
N2
trendline
elegans))
y = 0.0067x + 4.6818
R2 = 0.0732
Linear
(HK104
(C.
briggsae))
Baer et al. (2005) report mutational parameters for fecundity and fitness for three species, C.
0.25
Survivorship
genetic variation for mutation rate within D. melanogaster. Two recent studies with the nematode
Survivorship
and Fry (2004) has recently argued that the apparent discrepancy between studies is likely due to
strain of C. elegans and the HK104 strain of C. briggsae, with total fitness of HK104 declining on
HK104 (C.
briggsae)
Lynch, M and Walsh, B. 1998. Book: Genetics and Analysis of Quantitative Traits.
Mukai, T. 1964. Genetic structure of natural populations of Drosophila melanogaster. 1. Spontaneous
mutation rate of polygenes controlling viability. Genetics 50: 1-19.
Per-generation decline in relative fitness (ΔM), 25°
Mukai, T, Chigusa, SI, Crow, JF, Mettler, LE. 1972. Mutation rate and dominance of genes affecting
viability in Drosophila melanogaster. Genetics 72: 335-355.
Figure 3
Vassilieva, LL and Lynch, M. 1999. The rate of spontaneous mutation for life-history traits in
Caenorhabditis elegans. Genetics 151: 119-129.
provide the most important ultimate constraint on phenotypic evolution (Jones et al. 2003).
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