Slow recovery from inbreeding depression generated by the complex genetic architecture of segregating deleterious mutations

The deleterious effects of inbreeding have been of extreme importance to evolutionary biology, but it has been difficult to characterize the complex interactions between genetic constraints and selection that lead to fitness loss and recovery after inbreeding. Viruses, bacteria, and the selfing nematode Caenorhabditis elegans have been shown to be capable of rapid recovery from the fixation of novel deleterious mutation, however the potential for fitness recovery from fixation of segregating variation under inbreeding in outcrossing organisms is poorly understood. C. remanei is an outcrossing relative of C. elegans with high polymorphic variation and extreme inbreeding depression. Here we sought to characterize changes C. remanei in patterns of genomic diversity after ∼30 generations of inbreeding via brother-sister mating followed by several hundred generations of recovery at large population size. As expected, inbreeding led to a large decline in reproductive fitness, but unlike results from mutation accumulation experiments, recovery from inbreeding at large populations sizes generated only very moderate recovery in fitness after 300 generations. At the genomic level, we found that while 66% of ancestral segregating SNPs were fixed in the inbred population, this was far fewer than expected under neutral processes. Under recovery, 36 SNPs across 30 genes involved in alimentary, muscular, nervous and reproductive systems changed reproducibly across all replicates, indicating that strong selection for fitness recovery does exist but is likely mutationally limited due to the large number of potential targets. Our results indicate that recovery from inbreeding depression via new compensatory mutations is likely to be constrained by the large number of segregating deleterious variants present in natural populations, limiting the capacity for rapid evolutionary rescue of small populations.Impact SummaryInbreeding is defined as mating between close relatives and can have a large effect on the genetic diversity and fitness of populations. This has been recognized for over 100 years of study in evolutionary biology, but the specific genomic changes that accompany inbreeding and the loss of fitness are still not known. Evolutionary theory predicts that inbred populations lose fitness through the fixation of many deleterious alleles and it is not known if populations can recover fitness after prolonged periods of inbreeding and deleterious fixations, or how long recovery may take. These questions are particularly important for wild populations experiencing declines. In this study we use laboratory populations of the nematode worm Caenorhabditis remanei to analyze the loss of fitness and genomic changes that accompany inbreeding via brother-sister mating, and to track the populations as they recover from inbreeding at large population size over 300 generations. We find that: Total progeny decreased by 65% after inbreedingThere were many nucleotides in the genome that remained heterozygous after inbreedingThere was an excess of inbreeding-resistant nucleotides on the X chromosomeThe number of progeny remained low after 300 generations of recovery from inbreeding30 genes changed significant in allele frequency during recovery, including genes involved in the alimentary, muscular, nervous and reproductive systemsTogether, our results demonstrate that recovery from inbreeding is difficult, likely due to the fixation of numerous deleterious alleles throughout the genome.

Spontaneous Mutational Variances and Covariances for Fitness-Related Traits in Drosophila melanogaster

Starting from a completely homozygous population of Drosophila melanogaster, 176 lines were derived and independently maintained by a single brother-sister mating per generation. Three fitness-related traits were considered (fecundity, egg-to-pupa and pupa-to-adult viabilities). Mutational heritabilities of these traits and genetic correlations between all possible pairs were calculated from the between line divergence (codivergence), after 104–106 generations of mutation accumulation. Mutational heritabilities ranged from 0.60 × to 0.82 × 10−3 and correlations from −0.11 to 0.25. These values are likely to be underestimates due to selection against deleterious mutations. The distribution of the means of the lines was asymmetric, positive for fecundity and negative for both viability components. The coefficients of asymmetry are also likely to be biased, again due to selection. Extreme lines from the two tails of the distribution were examined in detail. Homozygous line effects were all negative for viability traits but predominantly positive for fecundity, indicating the fixation of mutations with positive effects on the latter. Corresponding heterozygous line effects showed a variable degree of dominance.

A reevaluation of data from competitive tests shows high levels of heterosis in Drosophila melanogaster.

We have analyzed the results from a range of procedures designed to measure the fitness under competitive conditions of inbred strains of Drosophila melanogaster, specifically strains which are homozygous for chromosome 2. All methods show a substantial reduction in fitness, ranging from an estimated 70-80% for single generation competition tests to 80-90% for a multiple generation population cage procedure. Furthermore, inbreeding through brother-sister mating reduces fitness by a comparable amount when allowance is made for the expected degree of homozygosity.

Inbreeding in genetic algebras

The treatment of selfing in genetic algebras [3] can be extended by the definition of an analogous operator on the copular algebra which corresponds to brother–sister mating, one on the duplicate of the copular algebra corresponding to mating between double first cousins, etc.

Inbreeding in genetic algebras

The treatment of selfing in genetic algebras [3] can be extended by the definition of an analogous operator on the copular algebra which corresponds to brother–sister mating, one on the duplicate of the copular algebra corresponding to mating between double first cousins, etc.

Experimental breeding and cytogenetics of the soft-furred rat, Millardia meltada

The soft-furred rat, Millardia meltada, has bred successfully in the laboratory for 10 generations of brother x sister mating. It is half way in size between the rat and the mouse, and is gentle and easy to handle. Thin body hair and incisor teeth are present in the newborn. Some individuals have low blood pressure. Chromosome number (2n) is 50. It differs in several characteristics from the rat and mouse, and could become a useful experimental animal in biomedical research.

FURTHER EVIDENCE FOR SELECTIVE DIFFERENCES BETWEEN ISOALLELES IN DROSOPHILA

ABSTRACT A number of separate strains of Drosophila pseudoobscura were inbred for 38 generations of brother-sister mating with forced heterozygosity for two alleles of either the octanol dehydrogenase or esterase-5 locus. Crosses were set up within each of these inbred lines such that simple mendelian ratios were expected, and eggs from these crosses were placed on media with additions of simple chemicals likely to interact with alleles of the two loci—octanol and ethanol for the ODH locus and tributyrin and triacetin for the E-5 locus. Similar crosses were set up involving parental flies with normally heterozygous genetic background as a control.—Significant deviations from mendelian expectation were observed in inbred E-5 flies grown on tributyrin, inbred ODH males grown on octanol, and inbred ODH females grown on ethanol. There was also a strong effect of octanol medium on males of one of the inbred E-5 lines, and a weak effect of tributyrin medium on ODH inbred females.—The probability that these results reflect interactions between these loci and the environment is assessed in the light of differences between the present results and those obtained at earlier stages of inbreeding.

The productivity of four inbred strains of Drosophila melanogaster

Four inbred strains of flies have been maintained by brother × sister mating since November, 1963. Counts of production per vial were made at 14 days, and the flies from the most productive vial were used as the parents of the next generation. For analysis the data were separated into three groups: vials with no production (blanks), vials with less than 20 flies (low production), and those with over 20 flies. The number of blanks did not change significantly in strain A but did show significant decreases in strains B and D. Until generation 60 the number of blanks per generation was not distributed in a Poisson series, but after this generation it was. The number of vials with low production was high in all strains for the first 20 generations and then decreased in widely different generations for each strain.Changes took place in all four strains but by different mechanisms. In strain A there was no increase in range, but the mode moved from 40 to 150 flies per vial and the proportion of low productive vials fell from 15% to 2% per generation. In strain D the low production vials fell from 22% to 6% and there was an extension of the range. Each of the strains shows definite trends of increase and decrease which last from 3 to 30 generations, and vary in slope from 0.3 to 13.8 flies per vial per generation. While we cannot determine how much or how many of these slopes are environmental, it can be argued that since many of the slopes of the four strains are not correlated, part of the cause is genetic. The changes in the direction of the trends show that phenotypic selection in small populations was not effective in accumulating and exploiting mutations for greater productivity.