Computer Simulation of the Joint Evolution of the Patterns of Polygenes, Transposable Elements, and Origin Identity Labels: Stabilizing Selection

A computer model of the populations dynamics of the patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of stabilizing selection for an additive quantitative trait (with the target value being 0.4 of the maximum) was analyzed. It was demonstrated that the final plateaus of the trait value and the frequencies of the active values of polygenes are reached rapidly, namely, within five to seven generations (the effective selection period). The inbreeding coefficient during this period also grows rapidly and then gradually increases eventually reaching 0.7. The inbreeding coefficient reaches plateau (at 1.0) only in generations 300–350, which suggests the effect of gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. By generation 100 of selection, the final patterns of TEs and OILs were not formed completely. Fixations and losses, especially those of the OIL pattern, were delayed. In general, however, the population heterogeneity with respect to the patterns studied does not stabilize. This heterogeneity decreases the case of stabilizing selection, although more slowly than in the cases of positive and negative selections.     

Negative selection and computer models of the joint evolution of the patterns of polygenes,transposable elements,and origin identity labels

Computer simulation of the population dynamics of the genomic patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of negative selection for an additive quantitative trait has been performed. It was demonstrated that active polygene alleles disappear very rapidly, whereas the patterns of TEs and OILs continue their evolution determined by strict selective inbreeding and gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. It was demonstrated that the final consensus pattern of OILs consists of the fragments of the original patterns, which contain neither active polygene alleles nor modifier or marker TEs. Neutral TE copies were present in the final pattern, as should be expected in the case of gene drift. Inbreeding coefficient increased steadily but by generation 100 reached values higher than 0.9. All other parameters and initial conditions being the same, the responses to negative and positive selections were asymmetric.     

Computer Simulation of Concerted Evolution of Patterns of Polygenes, Transposable Elements, and Origin Identity Labels: Negative Selection

Computer simulation of the population dynamics of the genomic patterns of polygenes, transposable elements (TEs), and origin identity labels (OILs) in the course of negative selection for an additive quantitative trait has been performed. It was demonstrated that active polygene alleles disappear very rapidly, whereas the patterns of TEs and OILs continue their evolution determined by strict selective inbreeding and gene drift. Dendrograms of the patterns of polygenes, TEs, and OILs were constructed for all generations. It was demonstrated that the final consensus pattern of OILs consists of the fragments of the original patterns, which contain neither active polygene alleles nor modifier or marker TEs. Neutral TE copies were present in the final pattern, as should be expected in the case of gene drift. Inbreeding coefficient increased steadily but by generation 100 reached values higher than 0.9. All other parameters and initial conditions being the same, the responses to negative and positive selections were asymmetric.     

Truncation family selection and nonsystematic inbreeding leads to a rapid fixation of a pattern of mobile genetic elements in a computer model

A computer simulation model of the population dynamics of a polygenic system and a pattern of mobile genetic elements (MGEs) under directional truncation selection for a quantitative trait was developed. Modifier MGEs were shown to be rapidly and adaptively fixed (or lost) together with the modified polygenes. Marker MGEs and independent MGE copies were fixed and lost just as rapidly but in a random manner. Using specific marking of initial haploid genomes and direct computing of the mean proportion of identical encounters at each locus in each generation, it was shown that the mean nonselective inbreeding coefficient F(n) dramatically increases in the course of selection, reaching values 0.7-0.9 in 15-20 generations. As a result, adaptive homozygotization of polygenes and modifier MGEs and random homozygotization of marker MGEs, independent MGE copies, and all other genes of the genome occurs. These results confirm the hypothesis on the "champion" polygene pattern advanced earlier to explain the data of selection experiments.     

Computer modeling of joint selection response of MGE patterns and a polygenic system]

Using computer simulation, selection response of three genome patterns--polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)--were studied. In each generation of selection, variability of each pattern type was described by on UPGMA tree. Stringent positive truncation selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95-96% and 70-80% of respectively enforced and non-enforced active polygenic alleles were fixed (2-3% and 16-17% lost). In all generations, Hkn < or = Dkn of the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85-88% (lost for 11-12%); marker MGEs, for 60-70 (lost for 21-25%); and independent copies, for 30-40 (lost for 50-60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16:3 for modifier MGEs, 15:6 for marker MGEs, and 25:28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random.     

The contribution of ancestry,chance, and past and ongoing selection to adaptive evolution

The relative contributions of ancestry, chance, and past and ongoing election to variation in one adaptive (larval feeding rate) and one seemingly nonadaptive (pupation height) trait were determined in populations ofDrosophila melanogaster adapting to either low or high larval densities in the laboratory. Larval feeding rates increased rapidly in response to high density, and the effects of ancestry, past selection and chance were ameliorated by ongoing selection within 15–20 generations. Similarly, in populations previously kept at high larval density, and then switched to low larval density, the decline of larval feeding rate to ancestral levels was rapid (15-20 generations) and complete, providing support for a previously stated hypothesis regarding the costs of faster feeding inDrosophila larvae. Variation among individuals was the major contributor to variation in pupation height, a trait that would superficially appear to be nonadaptive in the environmental context of the populations used in this study because it did not diverge between sets of populations kept at low versus high larval density for many generations. However, the degree of divergence among populations (FST) for pupation height was significantly less than expected for a selectively neutral trait, and we integrate results from previous studies to suggest that the variation for pupation height among populations is constrained by stabilizing selection, with a flat, plateau-like fitness function that, consequently, allows for substantial phenotypic variation within populations. Our results support the view that the genetic imprints of history (ancestry and past selection) in outbreeding sexual populations are typically likely to be transient in the face of ongoing selection and recombination. The results also illustrate the heuristic point that different forms of selection-for example directional versus stabilizing selection—acting on a trait in different populations may often not be due to differently shaped fitness functions, but rather due to differences in how the fitness function maps onto the actual distribution of phenotypes in a given population. We discuss these results in the light of previous work on reverse evolution, and the role of ancestry, chance, and past and ongoing selection in adaptive evolution.     

Response of the MGE 412 pattern to truncation selection of a quantitative trait in an isogenic line of drosophila after severe heat shock (SHS)

Positive and negative selection on the total length of two fragments of an interrupted longitudinal wing vein in an isogenic line of Drosophila melanogaster was accompanied by changes in the genomic localization pattern of MGE 412. Strong truncation selection was conducted in the population of effective size Ne = 160 for 50 generations. Twenty-six out of 35 polymorphic HHS-induced segments of MGE localization behaved as independent copies and markers, whereas 9 segments proved to be selective. The second group included "hot" segments of HHS transposition induction (43B, 97E, etc.). Thus, final consensus patterns of induced MGE transpositions have a random and an adaptive component in generation 50 of positive and negative selection. Selective patterns probably include modifier MGEs, which generate induced genetic regulatory variation of polygenes controlling the selected quantitative trait in the isogenic line after HHS.     

Computer system for simulating population dynamic patterns of polygenes and mobile genetic elements upon truncation selection for a quantitative trait

A computer system was developed for simulation of population dynamics of interacting polygene patterns and mobile genetic elements (MGEs) under selection for a quantitative trait. The system is stochastic (Monte Carlo) and takes into account the main sources of random change in the patterns (recombinations, transpositions, excisions), genetic drift, and determined trends of selection and other genetic processes in a finite population. Using this model, it is possible to analyze the dynamics of many population parameters that cannot be experimentally estimated: frequencies of polygenic alleles, proportions of adaptive and random fixations, average heterozygosities of polygenes and MGEs, coefficient of inbreeding, heritability, etc. In addition, the model can be used to test various hypotheses on polygene-MGE interaction.     

Pleiotropic Models of Polygenic Variation, Stabilizing Selection, and Epistasis

We show that in polymorphic populations many polygenic traits pleiotropically related to fitness are expected to be under apparent ``stabilizing selection' independently of the real selection acting on the population. This occurs, for example, if the genetic system is at a stable polymorphic equilibrium determined by selection and the nonadditive contributions of the loci to the trait value either are absent, or are random and independent of those to fitness. Stabilizing selection is also observed if the polygenic system is at an equilibrium determined by a balance between selection and mutation (or migration) when both additive and nonadditive contributions of the loci to the trait value are random and independent of those to fitness. We also compare different viability models that can maintain genetic variability at many loci with respect to their ability to account for the strong stabilizing selection on an additive trait. Let V(m) be the genetic variance supplied by mutation (or migration) each generation, V(g) be the genotypic variance maintained in the population, and n be the number of the loci influencing fitness. We demonstrate that in mutation (migration)-selection balance models the strength of apparent stabilizing selection is order V(m)/V(g). In the overdominant model and in the symmetric viability model the strength of apparent stabilizing selection is approximately 1/(2n) that of total selection on the whole phenotype. We show that a selection system that involves pairwise additive by additive epistasis in maintaining variability can lead to a lower genetic load and genetic variance in fitness (approximately 1/(2n) times) than an equivalent selection system that involves overdominance. We show that, in the epistatic model, the apparent stabilizing selection on an additive trait can be as strong as the total selection on the whole phenotype.     

Long-term response to genomic selection: effects of estimation method and reference population structure for different genetic architectures

Background

Genomic selection has become an important tool in the genetic improvement of animals and plants. The objective of this study was to investigate the impacts of breeding value estimation method, reference population structure, and trait genetic architecture, on long-term response to genomic selection without updating marker effects.

Methods

Three methods were used to estimate genomic breeding values: a BLUP method with relationships estimated from genome-wide markers (GBLUP), a Bayesian method, and a partial least squares regression method (PLSR). A shallow (individuals from one generation) or deep reference population (individuals from five generations) was used with each method. The effects of the different selection approaches were compared under four different genetic architectures for the trait under selection. Selection was based on one of the three genomic breeding values, on pedigree BLUP breeding values, or performed at random. Selection continued for ten generations.

Results

Differences in long-term selection response were small. For a genetic architecture with a very small number of three to four quantitative trait loci (QTL), the Bayesian method achieved a response that was 0.05 to 0.1 genetic standard deviation higher than other methods in generation 10. For genetic architectures with approximately 30 to 300 QTL, PLSR (shallow reference) or GBLUP (deep reference) had an average advantage of 0.2 genetic standard deviation over the Bayesian method in generation 10. GBLUP resulted in 0.6% and 0.9% less inbreeding than PLSR and BM and on average a one third smaller reduction of genetic variance. Responses in early generations were greater with the shallow reference population while long-term response was not affected by reference population structure.

Conclusions

The ranking of estimation methods was different with than without selection. Under selection, applying GBLUP led to lower inbreeding and a smaller reduction of genetic variance while a similar response to selection was achieved. The reference population structure had a limited effect on long-term accuracy and response. Use of a shallow reference population, most closely related to the selection candidates, gave early benefits while in later generations, when marker effects were not updated, the estimation of marker effects based on a deeper reference population did not pay off.     

Computer Simulation of Joint Selection Response of MGE Patterns and a Polygenic System

Using computer simulation, selection response of three genome patterns—polygenes, mobile genetic elements (MGEs), and labels of identity by origin (LIOs)—were studied. In each generation of selection, variability of each pattern type was described by an UPGMA tree. Stringent positive truncation (+) selection on an additive polygenic trait and recombination between segments of the genetic map were considered. MGEs were classified into three groups: modifiers (enhancers) of the polygenic expression, markers, and independent copies. It was shown that at generations 30 to 40, 95–96% and 70–80% of respectively enforced and non-enforced active polygenic alleles were fixed (2–3% and 16–17% lost). In all generations, H ⁿ _k max D ⁿ _kof the length of the maximal route along the tree. At the same time, modifier MGEs were fixed for 85–88% (lost for 11–12%); marker MGEs, for 60–70% (lost for 21–25%); and independent copies, for 30–40 (lost for 50–60%). The behavior of independent MGE copies was generally consistent with the predictions of the genetic drift theory, modifier MGEs behaved similarly to the modified polygenes, and marker MGEs exhibited intermediate properties. The LIO patterns showed rapid homozygotization: their variability dropped dramatically between generations 10 and 30. In F50, the final consensus pattern of polygenes included 16 out of 18 enforced and 18 out of 21 non-enforced polygenic alleles. The fixation/loss ratios were 16 : 3 for modifier MGEs, 15 : 6 for marker MGEs, and 25 : 28 (with 7 polymorphic) for independent copies. The LIO consensus pattern contained 13 out of 100 original markers, which formed 26 fragments of one to ten map segments in size; 21 fragments contained active polygenic alleles, and 14 of them had also modifier MGEs. Recombinational shuffling of patterns was not completed. In the course of selection, active polygenic alleles take along adjacent segments, including those containing modifier MGEs and markers. These constitute the conservative part of all consensus patterns while the remaining segments are random.     

Inbreeding and genetic disease in Sottunga, Finland

The contribution of inbreeding to the prevalence of recessive genetic diseases in the Aland Island parish of Sottunga is investigated. Genealogical data for 3,030 individuals spanning up to 15 generations were used to estimate inbreeding. This small island community shows a low average inbreeding value of .0031 for the period 1725-1975. A cohort analysis shows that inbreeding increased from 1750 to 1900, when maximum inbreeding for those born in Sottunga reached .0057. A sharp decline in inbreeding occurred thereafter. Individuals with island-born parents made the largest contributions to inbreeding in all time periods compared to those with one or two migrant parents. These trends are consistent with changing migration patterns and isolate breakdown in Aland since 1900. An analysis of pedigree development demonstrates that remote consanguinity contributed more to inbreeding through time than close consanguinity. Both the number of common ancestors and the number of paths of relationship between spouses increased dramatically through time, the latter at a much faster rate. The contribution to average inbreeding per path, however, diminished rapidly through time. This analysis indicates that inbreeding does not account for the high incidence of autosomal recessive disorders, such as tapetoretinal disease, found in the parish.     

Decoupling of differentiation between traits and their underlying genes in response to divergent selection

We dissected the relationship between genetic differentiation (Q(ST)) for a trait and its underlying genes (G(STq), differentiation for a quantitative locus) in an evolutionary context, with the aim of identifying the conditions in which these two measurements are decoupled. We used two parameters (θ(B) and θ(W)) scaling the contributions of inter- and intrapopulation allelic covariation between genes controlling the trait of interest. We monitored the changes in θ(B) and θ(W), Q(ST) and G(STq) over successive generations of divergent and stabilizing selection, in simulations for an outcrossing species with extensive gene flow. The dynamics of these parameters are characterized by two phases. Initially, during the earliest generations, differentiation of the trait increases very rapidly and the principal and immediate driver of Q(ST) is θ(B). During subsequent generations, G(STq) increases steadily and makes an equal contribution to Q(ST). These results show that selection first captures beneficial allelic associations at different loci at different populations, and then targets changes in allelic frequencies. The same patterns are observed when environmental change modifies divergent selection, as shown by the very rapid response of θ(B) to the changes of selection regimes. We compare our results with previous experimental findings and consider their relevance to the detection of molecular signatures of natural selection.     

Optimised parent selection and minimum inbreeding mating in small aquaculture breeding schemes: a simulation study

The effectiveness of low cost breeding scheme designs for small aquaculture breeding programmes were assessed for their ability to achieve genetic gain while managing inbreeding using stochastic simulation. Individuals with trait data were simulated over 15 generations with selection on a single trait. Combinations of selection methods, mating strategies and genetic evaluation options were evaluated with and without the presence of common environmental effects. An Optimal Parent Selection (OPS) method using semi-definite programming was compared with a truncation selection (TS) method. OPS constrains the rate of inbreeding while maximising genetic gain. For either selection method, mating pairs were assigned from the selected parents by either random mating (RM) or Minimum Inbreeding Mating (MIM), which used integer programming to determine mating pairs. Offspring were simulated for each mating pair with equal numbers of offspring per pair and these offspring were the candidates for selection of parents of the next generation. Inbreeding and genetic gain for each generation were averaged over 25 replicates. Combined OPS and MIM led to a similar level of genetic gain to TS and RM, but inbreeding levels were around 75% lower than TS and RM after 15 generations. Results demonstrate that it would be possible to manage inbreeding over 15 generations within small breeding programmes comprised of 30 to 40 males and 30 to 40 females with the use of OPS and MIM. Selection on breeding values computed using Best Linear Unbiased Prediction (BLUP) with all individuals genotyped to obtain pedigree information resulted in an 11% increase in genetic merit and a 90% increase in the average inbreeding coefficient of progeny after 15 generations compared with selection on raw phenotype. Genetic evaluation strategies using BLUP wherein elite individuals by raw phenotype are genotyped to obtain parentage along with a range of different samples of remaining individuals did not increase genetic progress in comparison to selection on raw phenotype. When common environmental effects on full-sib families were simulated, performance of small breeding scheme designs was little affected. This was because the majority of selection must anyway be applied within family due to inbreeding constraints.     

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.     

Prediction of rates of inbreeding in selected populations

A method is presented for the prediction of rate of inbreeding for populations with discrete generations. The matrix of Wright's numerator relationships is partitioned into 'contribution' matrices which describe the contribution of the Mendelian sampling of genes of ancestors in a given generation to the relationship between individuals in later generations. These contributions stabilize with time and the value to which they stabilize is shown to be related to the asymptotic rate of inbreeding and therefore also the effective population size, Ne approximately 2N/(mu 2r + sigma 2r), where N is the number of individuals per generation and mu r and sigma 2r are the mean and variance of long-term relationships or long-term contributions. These stabilized values are then predicted using a recursive equation via the concept of selective advantage for populations with hierarchical mating structures undergoing mass selection. Account is taken of the change in genetic parameters as a consequence of selection and also the increasing 'competitiveness' of contemporaries as selection proceeds. Examples are given and predicted rates of inbreeding are compared to those calculated in simulations. For populations of 20 males and 20, 40, 100 or 200 females the rate of inbreeding was found to increase by as much as 75% over the rate of inbreeding in an unselected population depending on mating ratio, selection intensity and heritability of the selected trait. The prediction presented here estimated the rate of inbreeding usually within 5% of that calculated from simulation.     

IS INBREEDING DEPRESSION LOWER IN MALADAPTED POPULATIONS? A QUANTITATIVE GENETICS MODEL

Despite abundant empirical evidence that inbreeding depression varies with both the environment and the genotypic context, theoretical predictions about such effects are still rare. Using a quantitative genetics model, we predict amounts of inbreeding depression for fitness emerging from Gaussian stabilizing selection on some phenotypic trait, on which, for simplicity, genetic effects are strictly additive. Given the strength of stabilizing selection, inbreeding depression then varies simply with the genetic variance for the trait under selection and the distance between the mean breeding value and the optimal phenotype. This allows us to relate the expected inbreeding depression to the degree of maladaptation of the population to its environment. We confront analytical predictions with simulations, in well-adapted populations at equilibrium, as well as in maladapted populations undergoing either a transient environmental shift, or gene swamping in heterogeneous habitats. We predict minimal inbreeding depression in situations of extreme maladaptation. Our model provides a new basis for interpreting experiments that measure inbreeding depression for the same set of genotypes in different environments, by demonstrating that the history of adaptation, in addition to environmental harshness per se, may account for differences in inbreeding depression.     

Coefficients of inbreeding and homozygosity in recurrent selection: The case of m linked loci

Summary Methods of calculating the coefficients of inbreeding and homozygosity in a finite population undergoing recurrent selection (self-select-intercross in succeeding generations) are investigated for the case of m linked loci and effective directional selection. These coefficients are derived in terms of vectors whose components reflect the various possible patterns of genes being identical at a given stage of the recurrent selection breeding program.For the case of two linked loci the progress of the panmictic index and/or the index of total heterozygosity through twenty-five cycles of recurrent selection is traced by means of computer-simulated populations ranging in sizes from ten through one hundred, assuming varying recombination probabilities, and assuming both minimum and maximum inbreeding selection patterns.Results indicate that the coefficient of relationship in the source population is extremely important in tracing the progress of the degree of inbreeding and/or total homozygosity, that linkage plays a major role in promoting heterozygosity in a recurrent selection system, and that careful intercrossing rather than random mating in alternate generations of the recurrent selection cycle is important in promoting maximum heterozygosity in the selected population. In the simulated populations the effect of small population sizes is observed and, in general, indications are that unless more than five complete recurrent cycles are contemplated, increasing the population size results in only relatively minor increases in panmixia, especially when linked loci are involved in the selected trait and when care is taken to avoid a maximum inbreeding selection pattern.     

Selection for non-diapause in the bumblebee Bombus terrestris, with notes on the effect of inbreeding

Bumblebees are generally believed to be annual insects. However, here we will show that under laboratory conditions the bumblebee Bombus terrestris (L.) can produce a second generation without a period of cold storage (diapause) or CO₂ narcosis (a method to break diapause). It is also shown that this so-called non-diapause trait can be selected for. The percentage of non-diapausing queens increased from 8% (minimum) to 97% (maximum) in two generations of selection. However, it was not possible to maintain isofemale non-diapause lines. Colonies of the fourth and fifth generation remained small (expressed in worker number) and produced a small number of queens. Also the percentage of queens that started laying eggs (defined as the percentage non-diapause) decreased in the fourth and fifth generations. To study whether this decline of the non-diapause lines was caused by inbreeding, a control experiment was conducted. In this control experiment queens were mated with their brothers (full-sib mating) for several generations and the number of queens that start egg laying was measured. This revealed that inbreeding can have a negative effect on the egg-laying capacities of queens thus causing the decline of inbred (non-diapause) lines.     

Inbreeding depression and male survivorship in Drosophila: implications for senescence theory

The extent to which inbreeding depression affects longevity and patterns of survivorship is an important issue from several research perspectives, including evolutionary biology, conservation biology, and the genetic analysis of quantitative traits. However, few previous inbreeding depression studies have considered longevity as a focal life-history trait. We maintained laboratory populations of Drosophila melanogaster at census population sizes of 2 and 10 male-female pairs for up to 66 generations and performed repeated assays of male survivorship throughout this time period. On average, significant levels of inbreeding depression were observed for median life span and age-specific mortality. For age-specific mortality, the severity of inbreeding depression increased over the life span. We found that a baseline inbreeding load of 0.307 lethal equivalents per gamete affected age-specific mortality, and that this value increased at a rate of 0.046 per day of the life span. With respect to some survivorship parameters, the differentiation of lineages was nonlinear with respect to the inbreeding coefficient, which suggested that nonadditive genetic variation contributed to variation among lineages. These findings provide insights into the genetic basis of longevity as a quantitative trait and have implications regarding the mutation-accumulation evolutionary explanation of senescence.