Calculation of the inbreeding coefficient

Wright's rule for calculating the inbreeding coefficient for an arbitrary pedigree is proven for both autosomal and X-linked loci.Supported by NSF Grant PHY-84-16691     

Sisters' curse: sexually antagonistic effects constrain the spread of a mitochondrial haplogroup superior in sperm competition

Maternal inheritance of mitochondria creates a sex-specific selective sieve with implications for male longevity, disease susceptibility and infertility. Because males are an evolutionary dead end for mitochondria, mitochondrial mutations that are harmful or beneficial to males but not females cannot respond directly to selection. Although the importance of this male/female asymmetry in evolutionary response depends on the extent to which mitochondrial mutations exert antagonistic effects on male and female fitness, few studies have documented sex-specific selection acting on mitochondria. Here, we exploited the discovery of two highly divergent mitochondrial haplogroups (A and B2) in central Panamanian populations of the pseudoscorpion Cordylochernes scorpioides. Next-generation sequencing and phylogenetic analyses suggest that selection on the ND4 and ND4L mitochondrial genes may partially explain sexually antagonistic mitochondrial effects on reproduction. Males carrying the rare B2 mitochondrial haplogroup enjoy a marked advantage in sperm competition, but B2 females are significantly less sexually receptive at second mating than A females. This reduced propensity for polyandry is likely to significantly reduce female lifetime reproductive success, thereby limiting the spread of the male beneficial B2 haplogroup. Our findings suggest that maternal inheritance of mitochondria and sexually antagonistic selection can constrain male adaptation and sexual selection in nature.     

Intralocus sexual conflict for fitness: sexually antagonistic alleles for testosterone

Intralocus sexual conflict occurs when a trait encoded by the same genetic locus in the two sexes has different optima in males and females. Such conflict is widespread across taxa, however, the shared phenotypic traits that mediate the conflict are largely unknown. We examined whether the sex hormone, testosterone (T), that controls sexual differentiation, contributes to sexually antagonistic fitness variation in the bank vole, Myodes glareolus. We compared (opposite-sex) sibling reproductive fitness in the bank vole after creating divergent selection lines for T. This study shows that selection for T was differentially associated with son versus daughter reproductive success, causing a negative correlation in fitness between full siblings. Our results demonstrate the presence of intralocus sexual conflict for fitness in this small mammal and that sexually antagonistic selection is acting on T. We also found a negative correlation in fitness between parents and their opposite-sex progeny (e.g. father-daughter), highlighting a dilemma for females, as the indirect genetic benefits of selecting reproductively successful males (high T) are lost with daughters. We discuss mechanisms that may mitigate this disparity between progeny quality.     

Effects of inbreeding on the magnitude of inbreeding depression in a highly self-fertilizing tree, Magnolia obovata

Inbreeding depression is one of the major selective forces driving the evolution of mating systems. Previous theories predict that long-lived plants will show a negative correlation between inbreeding depression and the level of inbreeding (as determined by an inbreeding coefficient) at maturity, but the extent of this correlation may vary among life stages because of variation in the genetic basis for inbreeding depression at different stages. To test this prediction, I used electrophoretic allozyme analysis and pollination experiments to examine the fixation index (F _is) at maturity and inbreeding depression in the early and late life stages of two populations with different outcrossing rates of a highly self-fertilizing tree, Magnolia obovata. The magnitude of inbreeding depression for early survival (δ _e) in an outcrossing population (t _m = 0.51; F _is = −0.015) was higher (δ _e = 0.97) than that in an inbreeding population (t _m = 0.18; F _is = 0.15; δ _e = 0.38). From these results, I estimated that both populations exhibited high inbreeding depression for late survival (δ _l) (0.94 in the outcrossing population and 0.93 in the inbreeding one) and lifetime survival (δ _t) (0.99 and 0.96, respectively). My results and previously published data demonstrate the predicted relationship between inbreeding depression and the level of inbreeding for early survival, but not for late survival. This suggests that there is a differential genetic basis for inbreeding depression at different life stages. The inbreeding depression for late survival appears to play a central role in the maintenance of reproductive traits that promote outcrossing in M. obovata.     

Intra-locus sexual conflict and sexually antagonistic genetic variation in hermaphroditic animals

Intra-locus sexual conflict results when sex-specific selection pressures for a given trait act against the intra-sexual genetic correlation for that trait. It has been found in a wide variety of taxa in both laboratory and natural populations, but the importance of intra-locus sexual conflict and sexually antagonistic genetic variation in hermaphroditic organisms has rarely been considered. This is not so surprising given the conceptual and theoretical association of intra-locus sexual conflict with sexual dimorphism, but there is no a priori reason why intra-locus sexual conflict cannot occur in hermaphroditic organisms as well. Here, I discuss the potential for intra-locus sexual conflict in hermaphroditic animals and review the available evidence for such conflict, and for the existence of sexually antagonistic genetic variation in hermaphrodites. I argue that mutations with asymmetric effects are particularly likely to be important in mediating sexual antagonism in hermaphroditic organisms. Moreover, sexually antagonistic genetic variation is likely to play an important role in inter-individual variation in sex allocation and in transitions to and from gonochorism (separate sexes) in simultaneous hermaphrodites. I also describe how sequential hermaphrodites may experience a unique form of intra-locus sexual conflict via antagonistic pleiotropy. Finally, I conclude with some suggestions for further research.     

Mitochondrial DNA nucleoids determine mitochondrial genetics and dysfunction

Mitochondrial DNA plays a crucial role in cellular homeostasis; however, the molecular mechanisms underlying mitochondrial DNA inheritance and propagation are only beginning to be understood. To ensure the distribution and propagation of the mitochondrial genome, mitochondrial DNA is packaged into macromolecular assemblies called nucleoids, composed of one or more copies of mitochondrial DNA and associated proteins. We review current research on the mitochondrial nucleoid, including nucleoid-associated proteins, nucleoid dynamics within the cell, potential mechanisms to ensure proper distribution of nucleoids, and the impact of nucleoid organization on mitochondrial dysfunction. The nucleoid is the molecular organizing unit of mitochondrial genetics, and is the site of interactions that ultimately determine the bioenergetic state of the cell as a whole. Current and future research will provide essential insights into the molecular and cellular interactions that cause bioenergetic crisis, and yield clues for therapeutic rescue of mitochondrial dysfunction.     

Potential bias in inbreeding depression estimates when using pedigree relationships to assess the degree of homozygosity for loci under selection

A potential bias in estimation of inbreeding depression when using pedigree relationships to assess the degree of homozygosity for loci under selection is indicated. A comparison of inbreeding coefficients based on either pedigree or genotypic frequencies indicated that, as a result of selection, the inbreeding coefficient based on pedigree might not correspond with the random drift of allelic frequencies. Apparent differences in average levels of both inbreeding coefficients were obtained depending on the genetic model (additive versus dominance, initial allelic frequencies, heritability) and the selection system assumed (no versus mass selection). In the absence of selection, allelic frequencies within a small population change over generations due to random drift, and the pedigree-based inbreeding coefficient gives a proper assessment of the accompanying probability of increased homozygosity within a replicate by indicating the variance of allelic frequencies over replicates. With selection, in addition to random drift, directional change in allelic frequencies is not accounted for by the pedigree-based inbreeding coefficient. This result implies that estimation of inbreeding depression for traits under either direct or indirect selection, estimated by a regression of performance on pedigree-based coefficients, should be carefully interpreted.Deceased     

Methods for predicting rates of inbreeding in selected populations

Summary In selected populations, families superior for the selected trait are likely to contribute more offspring to the next generation than inferior families and, as a consequence, the rate of inbreeding is likely to be higher in selected populations than in randomly mated populations of the same structure. Methods to predict rates of inbreeding in selected populations are discussed. The method of Burrows based on probabilities of coselection is reappraised in conjunction with the transition matrix method of Woolliams. The method of Latter based on variances and covariances of family size is also examined. These methods are one-generation approaches in the sense that they only account for selective advantage over a single generation, from parents to offspring. Two-generation methods are developed that account for selective advantage over two generations, from grandparent to grandoffspring as well as from parent to offspring. Predictions are compared to results from simulation. The best one-generation method was found to underpredict rates of inbreeding by 10–25%, and the two-generation methods were found to underpredict rates of inbreeding by 9–18%.     

On the classification of regular systems of inbreeding

Regular systems of inbreeding are defined as those with discrete, nonoverlapping generations and with the same number of individuals and mating pattern in every generation. Given the number of individuals in a generation, there are many possible regular mating systems. A notion of when two such mating systems are equivalent is introduced, and several necessary conditions are given for such an equivalence. The use of these conditions is illustrated for N = 2, 3, 4 and 5 individuals, and a complete enumeration has been found for these cases: the numbers of inequivalent mating systems are 1, 5, 57 and 858, respectively. The maximal eigenvalue of the matrix q that specifies the recursion relations satisfied by the probabilities of identity have also been found for these cases. For N = 3 and 4 (and 2 trivially), circular mating gives the slowest rate of approach to genetic uniformity of those systems that do evolve to uniformity, but for N = 5 there are two other mating systems that have a slower rate of convergence, and for N = 6 partial results show that there are many such examples.Deceased     

Effect of rate of inbreeding on inbreeding depression in Drosophila melanogaster

Summary This experiment was designed to study the relationship between rate of inbreeding and observed inbreeding depression of larval viability, adult fecundity and cold shock mortality in Drosophila melanogaster. Rates of inbreeding used were full-sib mating and closed lines of N=4 and N=20. Eight generations of mating in the N=20 lines, three generations in the N=4 lines and one generation of full-sib mating were synchronised to simultaneously produce individuals with an expected level of inbreeding coefficient (F) of approximately 0.25. Inbreeding depression for the three traits was significant at F=0.25. N=20 lines showed significantly less inbreeding depression than full-sib mated lines for larval viability at approximately the same level of F. A similar trend was observed for fecundity. No effect of rate of inbreeding depression was found for cold shock mortality, but this trait was measured with less precision than the other two. Natural selection acting on loci influencing larval viability and fecundity during the process of inbreeding could explain these results. Selection is expected to be more effective with slow rates of inbreeding because there are more generations and greater opportunity for selection to act before F=0.25 is reached. Selection intensities seem to have been different in the three traits measured. Selection was most intense for larval viability, less intense for fecundity and, perhaps, negligible at loci influencing cold shock mortality.     

Analysis of some regular systems of inbreeding

Summary A probabilistic method is used to calculate the asymptotic rate of loss of genetic variability for half-sib and first-cousin mating of an infinite number of individuals. For both systems of inbreeding, all probabilities of nonidentity by descent converge to zero at ultimate rates proportional to t ^–1/2, where t is the time in generations. The rate of decay is faster for half-sibs than for first cousins, the respective asymptotic allozygosities being 4(t)^–1/2 and 8(t)^–1/2.Supported by the National Science Foundation (Grant No. DEB77-21494).     

Short- and long-term benefits and detriments to recombination under antagonistic coevolution

We explored the evolution of recombination under antagonistic coevolution, concentrating on the equilibrium frequencies of modifier alleles causing recombination in initially nonrecombining populations. We found that the equilibrium level of recombination in the host depended not only on parasite virulence, but also on the strength of the modifier allele, and on whether or not the modifier was physically linked to the parasite interaction loci. Nonetheless, the maximum level of recombination for linked loci at equilibrium was about 0.3 (60% of free recombination) for interactions with highly virulent parasites; the level decreased for unlinked modifiers, and for lower levels of parasite virulence. We conclude that recombination spreads because it provides a combination of an immediate (next-generation) fitness benefit and a delayed (two or more generations) increase in the rate of response to directional selection. The relative impact of these two mechanisms depends on the virulence of parasites early in the spread of the modifier, but a trade-off between the two dictates the equilibrium modifier frequency for all nonzero virulences that we examined. In addition, population mean fitness was higher in populations at intermediate equilibria than populations fixed for free recombination or no recombination. The difference, however, was not enough on its own to overcome the two-fold cost of producing males.     

Evolution of proteins in mammalian cytoplasmic and mitochondrial ribosomes

Summary The proteins of cytoplasmic and mitochondrial ribosomes from the cow and the rat were analyzed by co-electrophoresis in two dimensional polyacrylamide gels to determine their relative evolutionary rates. In a pairwise comparison of individual ribosomal proteins (r-proteins) from the cow and the rat, over 85% of the cytoplasmic r-proteins have conserved electrophoretic properties in this system, while only 15% of the proteins of mitochondrial ribosomes from these animals fell into this category. These values predict that mammalian mitochondrial r-proteins are evolving about 13 times more rapidly than cytoplasmic r-proteins. Based on actual evolutionary rates for representative cytoplasmic r-proteins, this mitochondrial r-protein evolutionary rate corresponds to an amino acid substitution rate of 40×10^–10 per site per year, placing mitochondrial r-proteins in the category of rapidly evolving proteins. The mitochondrial r-proteins are apparently evolving at a rate comparable to that of the mitochondrial rRNA, suggesting that functional constraints act more or less equally on both kinds of molecules in the ribosome. It is significant that mammalian mitochondrial r-proteins are evolving more rapidly than cytoplasmic r-proteins in the same cell, since both sets of r-proteins are encoded by nuclear genes. Such a difference in evolutionary rates implies that the functional constraints operating on ribosomes are somewhat relaxed for mitochondrial ribosomes.Presented at the FEBS Symposium on Genome Organization and Evolution, held in Crete, Greece, September 1–5, 1986     

Biochemical and functional characterization of ORF138, a mitochondrial protein responsible for Ogura cytoplasmic male sterility in Brassiceae

In cytoplasmic male sterility (CMS), original mitochondrial genes contribute to sex determinism by provoking pollen abortion. The function of the encoded proteins remains unclear. We studied the ORF138 protein, responsible for the 'Ogura' CMS, which is both used in hybrid seed production and present in natural populations. We analyzed the biochemical and structural properties of this protein in male-sterile plants and in E. coli. We showed that this protein spontaneously forms dimers in vitro. Truncated variants of the protein, containing either the hydrophobic or the hydrophilic moiety, also spontaneously dimerize. By fractionating mitochondria, we showed that ORF138 was strongly associated with the inner mitochondrial membrane of male-sterile plants. Our results also strongly suggest that ORF138 forms oligomers in male-sterile plant mitochondria. In E. coli, ORF138 was associated with the plasma membrane, as shown by membrane fractionation, and formed oligomers. The production of this protein strongly inhibited bacterial growth, but not by inhibiting respiration. The observed toxic effects required both the hydrophilic and hydrophobic moieties of the protein.     

Comparison of ancestral and current-generation inbreeding in an experimental strawberry breeding population

Progenies from first-generation self, half-sib, full-sib, and cross fertilizations were generated to evaluate the magnitude of inbreeding depression for vegetative and production traits in strawberry. Tests were conducted to determine the linearity of trait mean depression with inbreeding rate (F) over this range of inbreeding values, as an indication of the presence of non-additive epistasis. A control population, for which a similar range of coancestry had accumulated over several cycles of breeding and selection, was also generated to compare the consequences of ancestral and current-generation inbreeding. Trait means for crosses among current-generation half-sibs, full-sibs, and selfs were 2–17%, 3–12%, and 14–45% lower than for unrelated crosses among the same set of parents, respectively. Linear regression of progeny means on current generation F was significantly negative for all traits and explained 17–44% of the variance among progeny means. Mean depression was largely linear over the range of inbreeding rates tested in this population, indicating the absence of epistasis for the traits evaluated. Conversely, (F) regressions of progeny means on pedigree inbreeding coefficients, where coancestry had accumulated over several cycles of breeding and selection, were uniformly non-significant and explained 0–10% of the variance among cross means. Further, multiple regression of progeny means for current-generation relatives on pedigree F failed to improve fit significantly over regression on current-generation F alone for all traits. Together, these results suggest that pedigree inbreeding coefficients are poor predictors of changes in homozygosity when populations are developed through multiple cycles of breeding and selection. They also imply that inbreeding depression will be of minor importance for strawberry breeding populations managed with adequate population sizes and strong directional selection.     

Population genetics of two asexually and sexually reproducing psocids species inferred by the analysis of mitochondrial and nuclear DNA sequences

Background

The psocids Liposcelis bostrychophila and L. entomophila (Psocoptera: Liposcelididae) are found throughout the world and are often associated with humans, food stores and habitations. These insects have developed high levels of resistance to various insecticides in grain storage systems. However, the population genetic structure and gene flow of psocids has not been well categorized, which is helpful to plan appropriate strategies for the control of these pests.

Methodology/Principal Findings

The two species were sampled from 15 localities in China and analyzed for polymorphisms at the mitochondrial DNA (Cytb) and ITS (ITS1-5.8S-ITS2) regions. In total, 177 individual L. bostrychophila and 272 individual L. entomophila were analysed. Both Cytb and ITS sequences showed high genetic diversity for the two species with haplotype diversities ranged from 0.154±0.126 to 1.000±0.045, and significant population differentiation (mean F _ST = 0.358 for L. bostrychophila; mean F _ST = 0.336 for L. entomophila) was also detected among populations investigated. A Mantel test indicated that for both species there was no evidence for isolation-by-distance (IBD). The neutrality test and mismatch distribution statistics revealed that the two species might have undergone population expansions in the past.

Conclusion

Both L. bostrychophila and L. entomophila displayed high genetic diversity and widespread population genetic differentiation within and between populations. The significant population differentiation detected for both psocids may be mainly due to other factors, such as genetic drift, inbreeding or control practices, and less by geographic distance since an IBD effect was not found.     

Prediction of rates of inbreeding in populations undergoing index selection

For populations undergoing mass selection, previous studies have shown that the rate of inbreeding is directly related to the mean and variance of long-term contributions from ancestors to descendants, and thus prediction of the rate of inbreeding can be achieved via the prediction of long-term contributions. In this paper, it is shown that the same relationship between the rate of inbreeding and long-term contributions is found when selection is based on an index of individual and sib records (index selection) and where sib records may be influenced by a common environment. In these situations, rates of inbreeding may be considerably higher than under mass selection. An expression for the rate of inbreeding is derived for populations undergoing index selection based on variances of (one-generation) family size and incorporating the concept of long-term selective advantage. When the mating structure is hierarchical, and when half-sib records are included in the index, the correlation between parental breeding values and the index values of their offspring is higher for male parents than female parents. This introduces an important asymmetry between the contributions of male and female ancestors to the evolution of inbreeding which is not present when selection is based on individual and/or full-sib records alone. The prediction equation for index selection accounts for this asymmetry. The prediction is compared to rates of inbreeding calculated from simulation. The prediction is good when family size is small relative to the number selected. The reasons for overprediction in other situations are discussed.     

Balancing selection response and rate of inbreeding by including genetic relationships in selection decisions

An iterative selection strategy, based on estimated breeding values (EBV) and average relationship among selected individuals, is proposed to optimise the balance between genetic response and inbreeding. Stochastic simulation was used to compare rates of inbreeding and genetic gain with those of other strategies. For a range of heritabilities, population sizes and mating ratios, the iterative strategy, denoted ADJEBV, outperforms other strategies, giving the greatest genetic gain at a given rate of inbreeding and the least breeding at a given genetic gain. Where selection is currently by truncation on the EBV, with a restriction on the number of full-sibs selected, it should be possible to maintain similar levels of genetic gain and inbreeding with a reduction in population size of 10–30%, by changing to the iterative strategy. If performance is measured by the reduction in cumulative inbreeding without losing more than a given amount of genetic gain relative to results obtained under truncation selection on the EBV, then with the EBV based on a family index, the performance of ADJEBV is greater at low heritability, and is generally greater than where EBV are based on individual records. When comparisons of genetic response and inbreeding are made for alternative breeding scheme designs, schemes which give higher genetic gain within acceptable inbreeding levels would usually be favoured. If comparisons are made on this basis, then the selection method used should be ADJEBV, which maximises the genetic gain for a given level of inbreeding. The results indicated that all selection strategies used to reduce inbreeding had very small effects on the variance of gain, and so differences in this respect are unlikely to affect choices among selection strategies. Selection criteria are recommended based on maximising a selection objective which specifies the desired balance between genetic gain and inbreeding.     

Prediction of additive and dominance effects in selected or unselected populations with inbreeding

Summary A genetic model with either 64 or 1,600 unlinked biallelic loci and complete dominance was used to study prediction of additive and dominance effects in selected or unselected populations with inbreeding. For each locus the initial frequency of the favourable allele was 0.2, 0.5, or 0.8 in different alternatives, while the initial narrow-sense heritability was fixed at 0.30. A population of size 40 (20 males and 20 females) was simulated 1,000 times for five generations. In each generation 5 males and 10 or 20 females were mated, with each mating producing four or two offspring, respectively. Breeding individuals were selected randomly, on own phenotypic performance or such yielding increased inbreeding levels in subsequent generations. A statistical model containing individual additive and dominance effects but ignoring changes in mean and genetic covariances associated with dominance due to inbreeding resulted in significantly biased predictions of both effects in generations with inbreeding. Bias, assessed as the average difference between predicted and simulated genetic effects in each generation, increased almost linearly with the inbreeding coefficient. In a second statistical model the average effect of inbreeding on the mean was accounted for by a regression of phenotypic value on the inbreeding coefficient. The total dominance effect of an individual in that case was the sum of the average effect of inbreeding and an individual effect of dominance. Despite a high mean inbreeding coefficient (up to 0.35), predictions of additive and dominance effects obtained with this model were empirically unbiased for each initial frequency in the absence of selection and 64 unlinked loci. With phenotypic selection of 5 males and only 10 females in each generation and 64 loci, however, predictions of additive and dominance effects were significantly biased. Observed biases disappeared with 1,600 loci for allelic frequencies at 0.2 and 0.5. Bias was due to a considerable change in allelic frequency with phenotypic selection. Ignoring both the covariance between additive and dominance effects with inbreeding and the change in dominance variance due to inbreeding did not significantly bias prediction of additive and dominance effects in selected or unselected populations with inbreeding.