Reduced inbreeding depression due to historical inbreeding in Drosophila melanogaster: evidence for purging

An important issue in conservation biology and the study of evolution is the extent to which inbreeding depression can be reduced or reversed by natural selection. If the deleterious recessive alleles causing inbreeding depression can be 'purged' by natural selection, outbred populations that have a history of inbreeding are expected to be less susceptible to inbreeding depression. This expectation, however, has not been realized in previous laboratory experiments. In the present study, we used Drosophila melanogaster as a model system to test for an association between inbreeding history and inbreeding depression. We created six 'purged' populations from experimental lineages that had been maintained at a population size of 10 male-female pairs for 19 generations. We then measured the inbreeding depression that resulted from one generation of full-sib mating in the purged populations and in the original base population. The magnitude of inbreeding depression in the purged populations was approximately one-third of that observed in the original base population. In contrast to previous laboratory experiments, therefore, we found that inbreeding depression was reduced in populations that have a history of inbreeding. The large purging effects observed in this study may be attributable to the rate of historical inbreeding examined, which was slower than that considered in previous experiments.     

Inbreeding and extinction: Effects of rate of inbreeding

Deleterious alleles may be removed (purged) bynatural selection in populations undergoinginbreeding. However, there is controversyregarding the effectiveness of selection inreducing the risk of extinction due toinbreeding, especially in relation to the rateof inbreeding. We evaluated the effect of therate of inbreeding on reducing extinction risk,in populations of Drosophila melanogastermaintained using full-sib mating (160replicates), or at effective population sizes(N _e) of 10 (80) or 20 (80).Extinction rates in the populations maintainedusing full-sib mating occurred at lower levelsof inbreeding than in the larger populations,whereas the two larger populations did notdiffer significantly from each other.Inbreeding coefficients at 50% extinction were0.62, 0.79 and 0.77 for the full-sib (N _e = 2.6), N _e = 10 and N _e = 20 treatments, respectively. Populations of N _e = 20 that remained extant after 60 generations, showed inbreeding depression, with the mean fitness of these populations being only 45% of the outbredcontrols. There was considerable variationamong the 31 inbred populations in fitness, butnone of the N _e = 20 populations hadfitness that was higher than the outbredcontrol. We conclude that purging may slow therate of extinction slightly, but it cannot berelied on to eliminate the deleterious effectsof inbreeding.     

Multigenerational inbreeding in <Emphasis Type="Italic">Succisa pratensis</Emphasis>: Effects on fitness components

We examined the effects of repeated inbreeding on fitness components of the long-lived perennial Succisa pratensis (Dipsacaceae). Plants from six populations differing in size were used to establish lines with expected inbreeding coefficients f of 0, 0.5 and 0.75. The effects of different inbreeding levels were measured for seed set, seed mass, percentage germination and seedling relative growth rate. Seed set decreased following one generation of inbreeding and seedling growth rate decreased after two generations of inbreeding. Our study indicated that the mutational load is difficult to purge and that continued inbreeding tends to affect important traits in S. pratensis. Although the partial dominance hypothesis for inbreeding depression seems to account for the results, the overdominance hypothesis cannot be ruled out completely. Overall, we conclude that the response of a long-lived plant, such as S. pratensis, to repeated inbreeding does not differ from that of other plant species with shorter life spans, surely because the mechanisms that account for inbreeding depression are universal for all plant species.     

Salmonid inbreeding: a review

We review the published literature oninbreeding and its consequences in salmonidfishes. Inbreeding reduces genetic variationwithin populations by decreasingheterozygosity, either through an increasedchance of sharing parental genes or a loss ofalleles from random genetic drift. Increasedinbreeding is often associated with a reductionin mean phenotypic value of one or more traitswith respect to fitness (inbreedingdepression). We identify several sources ofinbreeding in salmonids. Although inbreedingoccurs naturally, much of the evidence forinbreeding stems from direct or indirectresults of human activity. The potentialconsequences of inbreeding highlight theimportance of maintaining genetic diversity insalmonid populations. Our weak understandingof genetic interactions between cultured andwild salmonids has allowed widespread practicesthat can reduce genetic variability in naturalpopulations. Although studies have detectedinbreeding depression in salmonids, its geneticbasis has rarely been addressed in wild,anadromous salmon. The genetic basis ofinbreeding depression is complex, andevaluating its effects over the entire lifecycle remains challenging. The experimentalevidence nevertheless reinforces the importanceof maintaining genetic variation withinpopulations as a primary goal of conservationand management.     

Royal dynasties as human inbreeding laboratories: the Habsburgs

The European royal dynasties of the Early Modern Age provide a useful framework for human inbreeding research. In this article, consanguineous marriage, inbreeding depression and the purging of deleterious alleles within a consanguineous population are investigated in the Habsburgs, a royal dynasty with a long history of consanguinity over generations. Genealogical information from a number of historical sources was used to compute kinship and inbreeding coefficients for the Habsburgs. The marriages contracted by the Habsburgs from 1450 to 1750 presented an extremely high mean kinship (0.0628±0.009), which was the result of the matrimonial policy conducted by the dynasty to establish political alliances through marriage. A strong inbreeding depression for both infant and child survival was detected in the progeny of 71 Habsburg marriages in the period 1450–1800. The inbreeding load for child survival experienced a pronounced decrease from 3.98±0.87 in the period 1450–1600 to 0.93±0.62 in the period 1600–1800, but temporal changes in the inbreeding depression for infant survival were not detected. Such a reduction of inbreeding depression for child survival in a relatively small number of generations could be caused by elimination of deleterious alleles of a large effect according with predictions from purging models. The differential purging of the infant and child inbreeding loads suggest that the genetic basis of inbreeding depression was probably very different for infant and child survival in the Habsburg lineage. Our findings provide empirical support that human inbreeding depression for some fitness components might be purged by selection within consanguineous populations.     

Role of inbreeding depression and purging in captive breeding and restoration programmes

Inbreeding depression is a major force affecting the evolution and viability of small populations in captive breeding and restoration programmes. Populations that experience small sizes may be less susceptible to future inbreeding depression because they have been purged of deleterious recessive alleles. We review issues related to purging, as they apply to the management of small populations, and discuss an experiment we conducted examining purging in populations of mosquitofish (Gambusia affinis). Purging is an important process in many small populations, but the literature contains a diversity of responses to purging both within and among studies. With the exception that slow inbreeding results in more purging and less threat to population viability, there seem to be few consistent trends that aid in prediction of how a purging event will affect a population. In our examination of purging on population viability in mosquitofish, single or multiple bottlenecks do not appear to have resulted in any purging of the influence of genetic load on population growth. Rather, serial bottlenecks resulted in a marked decline in population growth and an increase in extinction. Our results, taken together with those of reviewed studies, suggest that in small populations there is great uncertainty regarding the success of any single purging event in eliminating inbreeding depression, together with the high likelihood that purging will depress population viability through the fixation of deleterious alleles. In management of captive breeding and restoration programmes, the common practice of avoiding inbreeding and small population sizes should be followed whenever possible.     

Mutation-selection balance accounting for genetic variation for viability in Drosophila melanogaster as deduced from an inbreeding and artificial selection experiment

We carried out an experiment of inbreeding and upward artificial selection for egg-to-adult viability in a recently captured population of Drosophila melanogaster, as well as computer simulations of the experimental design, in order to obtain information on the nature of genetic variation for this important fitness component. The inbreeding depression was linear with a rate of 0.70 +/- 0.11% of the initial mean per 1% increase in inbreeding coefficient, and the realized heritability was 0.06 +/- 0.07. We compared the empirical observations of inbreeding depression and selection response with computer simulations assuming a balance between the occurrence of partially recessive deleterious mutations and their elimination by selection. Our results suggest that a model assuming mutation-selection balance with realistic mutational parameters can explain the genetic variation for viability in the natural population studied. Several mutational models are incompatible with some observations and can be discarded. Mutational models assuming a low rate of mutations of large average effect and highly recessive gene action, and others assuming a high rate of mutations of small average effect and close to additive gene action, are compatible with all the observations.     

Host inbreeding increases susceptibility to ectoparasitism

Inbreeding, which increases homozygosity throughout the genome by increasing the proportion of alleles that are identical by descent, is expected to compromise resistance against parasitism. Here, we demonstrate that host inbreeding increases susceptibility to ectoparasitism in a natural fruit fly (Drosophila nigrospiracula) - mite (Macrocheles subbadius) association, and that this effect depends on host genetic background. Moreover, flies generated from reciprocal crosses between susceptible inbred lines exhibited elevated levels of resistance similar to that in the mass-bred base population, confirming in reverse direction the causative link between expected heterozygosity and resistance. We also show that inbreeding reduces the host's ability to sustain energetically expensive behaviours, and that host exhaustion dramatically increases susceptibility. These findings suggest that inbreeding depression for resistance results from an inability to sustain defensive behaviours because of compromised physiological competence.     

Genetic rescue and inbreeding depression in Mexican wolves

Although inbreeding can reduce individual fitness and contribute to population extinction, gene flow between inbred but unrelated populations may overcome these effects. Among extant Mexican wolves (Canis lupus baileyi), inbreeding had reduced genetic diversity and potentially lowered fitness, and as a result, three unrelated captive wolf lineages were merged beginning in 1995. We examined the effect of inbreeding and the merging of the founding lineages on three fitness traits in the captive population and on litter size in the reintroduced population. We found little evidence of inbreeding depression among captive wolves of the founding lineages, but large fitness increases, genetic rescue, for all traits examined among F1 offspring of the founding lineages. In addition, we observed strong inbreeding depression among wolves descended from F1 wolves. These results suggest a high load of deleterious alleles in the McBride lineage, the largest of the founding lineages. In the wild, reintroduced population, there were large fitness differences between McBride wolves and wolves with ancestry from two or more lineages, again indicating a genetic rescue. The low litter and pack sizes observed in the wild population are consistent with this genetic load, but it appears that there is still potential to establish vigorous wild populations.     

Seasonal stress drives predictable changes in inbreeding depression in field-tested captive populations of Drosophila melanogaster

Recent meta-analyses conducted across a broad range of taxa have demonstrated a strong linear relationship between the change in magnitude of inbreeding depression under stress and stress level, measured as fitness loss in outbred individuals. This suggests that a general underlying response may link stress and inbreeding depression. However, this relationship is based primarily on laboratory data, and it is unknown whether natural environments with multiple stressors and fluctuating stress levels alter how stress affects inbreeding depression. To test whether the same pattern persists in the field, we investigated the effect of seasonal variation on stress level and inbreeding depression in a 3-year field study measuring the productivity of captive populations of inbred and outbred Drosophila melanogaster. We found cold winter temperatures were most stressful and induced the greatest inbreeding depression. Furthermore, these data, collected under natural field conditions, conformed to the same predictive linear relationship seen in Drosophila laboratory studies, with inbreeding depression increasing by 0.17 lethal equivalents for every 10 per cent increase in stress level. Our results suggest that under natural conditions stress level is a primary determinant of the magnitude of inbreeding depression and should be considered when assessing extinction vulnerability in small populations.     

Environmental dependence of inbreeding depression and purging in Drosophila melanogaster

Elimination or reduction of inbreeding depression by natural selection at the contributing loci (purging) has been hypothesized to effectively mitigate the negative effects of inbreeding in small isolated populations. This may, however, only be valid when the environmental conditions are relatively constant. We tested this assumption using Drosophila melanogaster as a model organism. By means of chromosome balancers, chromosomes were sampled from a wild population and their viability was estimated in both homozygous and heterozygous conditions in a favourable environment. Around 50% of the chromosomes were found to carry a lethal or sublethal mutation, which upon inbreeding would cause a considerable amount of inbreeding depression. These detrimentals were artificially purged by selecting only chromosomes that in homozygous condition had a viability comparable to that of the heterozygotes (quasi-normals), thereby removing most deleterious recessive alleles. Next, these quasi-normals were tested both for egg-to-adult viability and for total fitness under different environmental stress conditions: high-temperature stress, DDT stress, ethanol stress, and crowding. Under these altered stressful conditions, particularly for high temperature and DDT, novel recessive deleterious effects were expressed that were not apparent under control conditions. Some of these chromosomes were even found to carry lethal or near-lethal mutations under stress. Compared with heterozygotes, homozygotes showed on average 25% additional reduction in total fitness. Our results show that, except for mutations that affect fitness under all environmental conditions, inbreeding depression may be due to different loci in different environments. Hence purging of deleterious recessive alleles can be effective only for the particular environment in which the purging occurred, because additional load will become expressed under changing environmental conditions. These results not only indicate that inbreeding depression is environment dependent, but also that inbreeding depression may become more severe under changing stressful conditions. These observations have significant consequences for conservation biology.     

Comparing molecular measures for detecting inbreeding depression

Correlations between heterozygosity and components of fitness have been investigated in natural populations for over 20 years. Positive correlations between a trait of interest and heterozygosity (usually measured at allozyme loci) are generally recognized as evidence of inbreeding depression. More recently, molecular markers such as microsatellites have been employed for the same purpose. A typical study might use around five to ten markers. In this paper we use a panel of 71 microsatellite loci to: (1) Compare the efficacy of heterozygosity and a related microsatellite‐specific variable, mean d², in detecting inbreeding depression; (2) Examine the statistical power of heterozygosity to detect such associations. We performed our analyses in a wild population of red deer (Cervus elaphus) in which inbreeding depression in juvenile traits had previously been detected using a panel of nine markers. We conclude that heterozygosity‐based measures outperform mean d²‐based measures, but that power to detect heterozygosity‐fitness associations is nonetheless low when ten or fewer markers are typed.     

Evidence of inbreeding depression but not inbreeding avoidance in a natural house sparrow population

Inbreeding is common in small and threatened populations and often has a negative effect on individual fitness and genetic diversity. Thus, inbreeding can be an important factor affecting the persistence of small populations. In this study, we investigated the effects of inbreeding on fitness in a small, wild population of house sparrows (Passer domesticus) on the island of Aldra, Norway. The population was founded in 1998 by four individuals (one female and three males). After the founder event, the adult population rapidly increased to about 30 individuals in 2001. At the same time, the mean inbreeding coefficient among adults increased from 0 to 0.04 by 2001 and thereafter fluctuated between 0.06 and 0.10, indicating a highly inbred population. We found a negative effect of inbreeding on lifetime reproductive success, which seemed to be mainly due to an effect of inbreeding on annual reproductive success. This resulted in selection against inbred females. However, the negative effect of inbreeding was less strong in males, suggesting that selection against inbred individuals is at least partly sex specific. To examine whether individuals avoided breeding with close relatives, we compared observed inbreeding and kinship coefficients in the population with those obtained from simulations of random mating. We found no significant differences between the two, indicating weak or absent inbreeding avoidance. We conclude that there was inbreeding depression in our population. Despite this, birds did not seem to actively avoid mating with close relatives, perhaps as a consequence of constraints on mating possibilities in such a small population.     

The genetic consequences of fluctuating inbreeding depression and the evolution of plant selfing rates

The magnitude of inbreeding depression, a central parameter in the evolution of plant mating systems, can vary depending on environmental conditions. However, the underlying genetic mechanisms causing environmental fluctuations in inbreeding depression, and the consequences of this variation for the evolution of self‐fertilization, have been little studied. Here, we consider temporal fluctuations of the selection coefficient in an explicit genetic model of inbreeding depression. We show that substantial variance in inbreeding depression can be generated at equilibrium by fluctuating selection, although the simulated variance tends to be lower than has been measured in experimental studies. Our simulations also reveal that purging of deleterious mutations does not depend on the variance in their selection coefficient. Finally, an evolutionary analysis shows that, in contrast to previous theoretical approaches, intermediate selfing rates are never evolutionarily stable when the variation in inbreeding depression is due to fluctuations in the selection coefficient on deleterious mutations.     

Population type can influence the magnitude of inbreeding depression in Clarkia concinna (Onagraceae)

Fragmented populations may face high risk of extinction due to the deleterious consequences of increased inbreeding or of genetic drift in small and isolated populations. Theories on the mechanisms of inbreeding depression predict that the severity of inbreeding depression can eventually decrease in populations that persistently inbreed, and hence populations that are isolated through habitat fragmentation might experience a decrease in inbreeding depression over time. In this study, we tested this hypothesis using the patchily distributed, outcrossing annual plant, Clarkia concinna concinna (Onagraceae), which naturally experiences many fragmentation effects. We collected seeds from isolated and central subpopulations and created artificially inbred and outcrossed lines. Progeny from these crosses were planted into the field and greenhouse and assayed for fitness traits over the course of a growing season. Overall, inbreeding depression was substantial, ranging as high as 0.76 (for cumulative fitness in the field), and significant for plant height, fecundity, and above-ground biomass in all experiments. No inbreeding depression was detected for germination or survival rates in the greenhouse experiments, but in the field, survival was significantly depressed for inbred progeny. There was no evidence to support our hypothesis that increased inbreeding in isolated populations would lead to the purging of deleterious alleles and a decrease in the severity inbreeding depression. The most likely hypothesis to explain our results is that purging is not occurring more strongly in the isolated populations due to details of a number of genetic factors (e.g., selection against deleterious alleles is inconsistent or insufficient, or drift has caused fixation of deleterious alleles in these populations). This study supports the view that even when inbreeding depression is predicted to be less problematic, it may still be an important force influencing the fitness of populations. This revised version was published online in July 2006 with corrections to the Cover Date.     

No evidence of inbreeding avoidance or inbreeding depression in a social carnivore

Dispersal by young mammals away from their natal site is generallythought to reduce inbreeding, with its attendant negative fitnessconsequences. Genetic data from the dwarf mongoose, a pack-livingcarnivore common in African savannas, indicate that there areexceptions to this generalization. In dwarf mongoose populationsin the Serengeti National Park, Tanzania, breeding pairs arecommonly related, and close inbreeding has no measurable effecton offspring production or adult survival. Inbreeding occursbecause average relatedness among potential mates within a packis high, because mating patterns within the pack are randomwith respect to the relatedness of mates, and because dispersaldoes little to decrease the relatedness among mates. Young femalesare more likely to leave a pack when the dominant male is aclose relative but are relatively infrequent dispersers. Youngmales emigrate at random with respect to the relatedness ofthe dominant female and tend to disperse to packs that containgenetically similar individuals.[Behav Ecol 7: 480–489(1996)]     

Sex‐specific effects of inbreeding in wild‐caught Drosophila melanogaster under benign and stressful conditions

In animal populations, sib mating is often the primary source of inbreeding depression (ID). We used recently wild‐caught Drosophila melanogaster to test whether such ID is amplified by environmental stress and, in males, by sexual selection. We also investigated whether increased ID because of stress (increased larval competition) persisted beyond the stressed stage and whether the effects of stress and sexual selection interacted. Sib mating resulted in substantial cumulative fitness losses (egg to adult reproduction) of 50% (benign) and 73% (stressed). Stress increased ID during the larval period (23% vs. 63%), but not during post‐stress reproductive stages (36% vs. 31%), indicating larval stress may have purged some adult genetic load (although ID was uncorrelated across stages). Sexual selection exacerbated inbreeding depression, with inbred male offspring suffering a higher reproductive cost than females, independent of stress (57% vs. 14% benign, 49% vs. 11% stress).     

The effect of fast created inbreeding on litter size and body weights in mice

This study was designed to reveal any differences in effects of fast created versus total inbreeding on reproduction and body weights in mice. A line selected for large litter size for 124 generations (H) and a control line (K) maintained without selection for the same number of generations were crossed (HK) and used as a basis for the experiment. Within the HK cross, full sib, cousin or random mating were practised for two generations in order to create new inbreeding (IB_F) at a fast rate. In the first generation of systematic mating, old inbreeding was regenerated in addition to creation of new inbreeding from the mating design giving total inbreeding (IB_T). The number of pups born alive (NBA) and body weights of the animals were then analysed by a model including both IB_T and IB_F. The IB_T of the dam was in the present study found to reduce the mean NBA with -0.48 (± 0.22) (p < 0.05) pups per 10% increase in the inbreeding coefficient, while the additional effect of IB_F was -0.42 (± 0.27). For the trait NBA per female mated, the effect of IB_T was estimated to be -0.45 (± 0.29) per 10% increase in the inbreeding coefficient and the effect of IB_F was -0.90 (± 0.37) (p < 0.05) pups. In the present study, only small or non-significant effects of IB_F of the dam could be found on sex-ratio and body weights at three and six weeks of age in a population already adjusted for IB_T.