Impact of founder population, drift and selection on the genetic diversity of a recently translocated tree population

Recently established, temperate tree populations combine a high level of differentiation for adaptive traits, suggesting rapid genetic evolution, with a high level of genetic diversity within population, suggesting a limited impact of genetic drift and purifying selection. To study experimentally the evolutionary forces in a recently established population, we assessed the spatial and temporal patterns of genetic diversity within a disjunct population of Cedrus atlantica established 140 years ago in south-eastern France from a North African source. The population is expanding through natural regeneration. Three generations were sampled, including founder trees. We analysed 12 isozyme loci, three of which were previously found in tight association with selected genes, and quantitative traits. No bottleneck effect was detected in the founder generation, but a simple test of allelic association revealed an initial disequilibrium which disappeared in the following generations. The impact of genetic drift during secondary evolution was limited, as suggested by the weak temporal differentiation. The genetic load was not reduced after 3 generations, and the quantitative variation for adaptive traits did not change either. Thus, initial genetic changes first proceed from a rapid re-organisation of the diversity through mating and recombination, whereas genetic erosion through drift and selection is delayed due to temporal and spatial stochasticity. Two life-history traits of trees contribute to slowing down the processes of genetic erosion: perenniality and large spatial scale. Thus, one would expect recently established tree populations to have a higher diversity than older ones, which seems in accordance with experimental surveys.     

Serial founder effects during range expansion: a spatial analog of genetic drift

Range expansions cause a series of founder events. We show that, in a one-dimensional habitat, these founder events are the spatial analog of genetic drift in a randomly mating population. The spatial series of allele frequencies created by successive founder events is equivalent to the time series of allele frequencies in a population of effective size ke, the effective number of founders. We derive an expression for ke in a discrete-population model that allows for local population growth and migration among established populations. If there is selection, the net effect is determined approximately by the product of the selection coefficients and the number of generations between successive founding events. We use the model of a single population to compute analytically several quantities for an allele present in the source population: (i) the probability that it survives the series of colonization events, (ii) the probability that it reaches a specified threshold frequency in the last population, and (iii) the mean and variance of the frequencies in each population. We show that the analytic theory provides a good approximation to simulation results. A consequence of our approximation is that the average heterozygosity of neutral alleles decreases by a factor of 1-1/(2ke) in each new population. Therefore, the population genetic consequences of surfing can be predicted approximately by the effective number of founders and the effective selection coefficients, even in the presence of migration among populations. We also show that our analytic results are applicable to a model of range expansion in a continuously distributed population.     

The genetic dissection of complex traits in a founder population

We estimated broad heritabilities (H(2)) and narrow heritabilities (h(2)) and conducted genomewide screens, using a novel association-based mapping approach for 20 quantitative trait loci (QTLs) among the Hutterites, a founder population that practices a communal lifestyle. Heritability estimates ranged from.21 for diastolic blood pressure (DBP) to.99 for whole-blood serotonin levels. Using a multipoint method to detect association under a recessive model we found evidence of major QTLs for six traits: low-density lipoprotein (LDL), triglycerides, lipoprotein (a) (Lp[a]), systolic blood pressure (SBP), serum cortisol, and whole-blood serotonin. Second major QTLs for Lp(a) and for cortisol were identified using a single-point method to detect association under a general two-allele model. The heritabilities for these six traits ranged from.37 for triglycerides to.99 for serotonin, and three traits (LDL, SBP, and serotonin) had significant dominance variances (i.e., H(2) > h(2)). Surprisingly, there was little correlation between measures of heritability and the strength of association on a genomewide screen (P>.50), suggesting that heritability estimates per se do not identify phenotypes that are influenced by genes with major effects. The present study demonstrates the feasibility of genomewide association studies for QTL mapping. However, even in this young founder population that has extensive linkage disequilibrium, map densities <5 cM may be required to detect all major QTLs.     

Re-creation of the genetic composition of a founder population

Human ethnic groups are frequently comprised of two or more founder populations. One of these founding populations is often available for contemporary sampling. We describe a method for reconstructing the composition of a missing founder population using the highly informative haplotypes comprising the HLA system. An application of the method is demonstrated using bone marrow registry samples of African Americans. We use contemporary samples of African Americans and European Americans to derive haplotypes of the West African founder populations. This approach may also be useful for reconstructing ancestral haplotypes for regions elsewhere in the genome.     

Generalized population models and the nature of genetic drift

The Wright–Fisher model of allele dynamics forms the basis for most theoretical and applied research in population genetics. Our understanding of genetic drift, and its role in suppressing the deterministic forces of Darwinian selection has relied on the specific form of sampling inherent to the Wright–Fisher model and its diffusion limit. Here we introduce and analyze a broad class of forward-time population models that share the same mean and variance as the Wright–Fisher model, but may otherwise differ. The proposed class unifies and further generalizes a number of population-genetic processes of recent interest, including the Λ and Cannings processes. Even though these models all have the same variance effective population size, they encode a rich diversity of alternative forms of genetic drift, with significant consequences for allele dynamics. We characterize in detail the behavior of standard population-genetic quantities across this family of generalized models. Some quantities, such as heterozygosity, remain unchanged; but others, such as neutral absorption times and fixation probabilities under selection, deviate by orders of magnitude from the Wright–Fisher model. We show that generalized population models can produce startling phenomena that differ qualitatively from classical behavior — such as assured fixation of a new mutant despite the presence of genetic drift. We derive the forward-time continuum limits of the generalized processes, analogous to Kimura’s diffusion limit of the Wright–Fisher process, and we discuss their relationships to the Kingman and non-Kingman coalescents. Finally, we demonstrate that some non-diffusive, generalized models are more likely, in certain respects, than the Wright–Fisher model itself, given empirical data from Drosophila populations.     

The effective founder effect in a spatially expanding population

The gradual loss of diversity and the establishment of clines in allele frequencies associated with range expansions are patterns observed in many species, including humans. These patterns can result from a series of founder events occurring as populations colonize previously unoccupied areas. We develop a model of an expanding population and, using a branching process approximation, show that spatial gradients reflect different amounts of genetic drift experienced by different subpopulations. We then use this model to measure the net average strength of the founder effect, and we demonstrate that the predictions from the branching process model fit simulation results well. We further show that estimates of the effective founder size are robust to potential confounding factors such as migration between subpopulations. We apply our method to data from Arabidopsis thaliana. We find that the average founder effect is approximately three times larger in the Americas than in Europe, possibly indicating that a more recent, rapid expansion occurred.     

Habitat geometry, population viscosity and the rate of genetic drift

In all natural populations, individuals located close to one another tend to interact more than those further apart. The extent of population viscosity can have important implications for ecological and evolutionary processes. Here we develop a spatially explicit population model to examine how the rate of genetic drift depends upon both spatial population structure and habitat geometry. The results show that the time to fixation for a new and selectively neutral mutation is dramatically increased in viscous populations. Furthermore, in viscous populations the time to fixation depends critically on habitat geometry. Fixation time for populations of identical size increases markedly as landscape width decreases and length increases. We suggest that similar effects will also be important in metapopulations, with the spatial arrangement of subpopulations and their connectivity likely to determine the rate of drift. We argue that the recent increases in computer power should facilitate major advances in our understanding of evolutionary landscape ecology over the next few years, and suggest that the time is ripe for a unification of spatial population dynamics theory, landscape ecology and population genetics.     

Unbiased estimator for genetic drift and effective population size

Amounts of genetic drift and the effective size of populations can be estimated from observed temporal shifts in sample allele frequencies. Bias in this so-called temporal method has been noted in cases of small sample sizes and when allele frequencies are highly skewed. We characterize bias in commonly applied estimators under different sampling plans and propose an alternative estimator for genetic drift and effective size that weights alleles differently. Numerical evaluations of exact probability distributions and computer simulations verify that this new estimator yields unbiased estimates also when based on a modest number of alleles and loci. At the cost of a larger standard deviation, it thus eliminates the bias associated with earlier estimators. The new estimator should be particularly useful for microsatellite loci and panels of SNPs, representing a large number of alleles, many of which will occur at low frequencies.     

Mitogenomic and microsatellite variation in descendants of the founder population of Newfoundland: high genetic diversity in an historically isolated population

The island of Newfoundland, the first of England's overseas colonies, was settled from the 17th century onward by restricted numbers of English, Irish, and French immigrants, in small "outport" communities that have maintained geographic, religious, and linguistic isolation to the latest generations. To measure the extent of modification and loss of genetic variation through founder effect, drift, and inbreeding in this historically isolated population, we analyzed the complete mitochondrial DNA (mtDNA) genomes and 14 microsatellite loci from each of 27 individuals with matrilineal ancestries extending to the colonial period. Every individual has a unique mtDNA genome sequence. All but one of these genomes are assignable to one of five major (H,J,K,T, and U) or minor (I) European haplogroups. The possibility of homoplasy at single nucleotide polymorphism (SNP) sites that define subtypes within the H haplogroup is discussed. Observed haplogroup proportions do not differ significantly from those of western Europeans or between English and Irish Newfoundlanders. The exceptional individual is a member of haplogroup A2, who appears to be the descendant of a Mi'kmaq First Nations mother and a French father, a common marriage pattern in the early settlement of Newfoundland. Microsatellite diversity is high (HE = 0.763), unstructured with respect to mtDNA haplotype or ethnicity, and there is no evidence of linkage disequilibrium. There is a small but significant degree of inbreeding (FIS = 0.0174). Collection of whole mtDNA genome data was facilitated by the use of microarray sequencing, and we describe a simple algorithm that is 99.67% efficient for sequence recovery.     

Limits to genetic bottlenecks and founder events imposed by the Allee effect

The Allee effect can result in a negative population growth rate at low population density. Consequently, populations below a minimum (critical) density are unlikely to persist. A lower limit on population size should constrain the loss of genetic variability due to genetic drift during population bottlenecks or founder events. We explored this phenomenon by modeling changes in genetic variability and differentiation during simulated bottlenecks of the alpine copepod, Hesperodiaptomus shoshone. Lake surveys, whole-lake re-introduction experiments and model calculations all indicate that H. shoshone should be unlikely to establish or persist at densities less than 0.5–5 individuals m⁻³. We estimated the corresponding range in minimum effective population size using the distribution of habitat (lake) sizes in nature and used these values to model the expected heterozygosity, allelic richness and genetic differentiation resulting from population bottlenecks. We found that during realistic bottlenecks or founder events, >90% of H. shoshone populations in the Sierra Nevada may be resistant to significant changes in heterozygosity or genetic distance, and 70–75% of populations may lose <10% of allelic richness. We suggest that ecological constraints on minimum population size be considered when using genetic markers to estimate historical population dynamics.     

A threefold genetic allee effect: population size affects cross-compatibility, inbreeding depression and drift load in the self-incompatible Ranunculus reptans

A decline in population size can lead to the loss of allelic variation, increased inbreeding, and the accumulation of genetic load through drift. We estimated the fitness consequences of these processes in offspring of controlled within-population crosses from 13 populations of the self-incompatible, clonal plant Ranunculus reptans. We used allozyme allelic richness as a proxy for long-term population size, which was positively correlated with current population size. Crosses between plants of smaller populations were less likely to be compatible. Inbreeding load, assessed as the slope of the relationship between offspring performance and parental kinship coefficients, was not related to population size, suggesting that deleterious mutations had not been purged from small populations. Offspring from smaller populations were on average more inbred, so inbreeding depression in clonal fitness was higher in small populations. We estimated variation in drift load from the mean fitness of outbred offspring and found enhanced drift load affecting female fertility within small populations. We conclude that self-incompatibility systems do not necessarily prevent small populations from suffering from inbreeding depression and drift load and may exacerbate the challenge of finding suitable mates.     

Estimation of genetic variability of the founder population in a conservation scheme using microsatellites

In a conservation programme with genealogical records it is possible to estimate the amount of variability of the founder population from a measure of the similarity among the individuals in the current population based on microsatellite markers. Here we compare three available methods and we shown that the one based on the molecular coancestry coefficient should be preferred.     

The founder effect and deleterious genes

During the rapid growth of a population from a few founders, a single deleterious gene in a founder can attain an appreciable frequency in later generations. A computer simulation, which has the population double itself in early generations, indicates a lethal could attain a frequency of 0.1. Since deleterious recessive genes are eliminated from large populations at a very slow rate, variations in their frequencies in present major human populations may be due to the founder effect during earlier rapid expansion.     

Cytonuclear disequilibrium and genetic drift in a natural population of ponderosa pine

We measured the cytonuclear disequilibrium between 11 nuclear allozyme loci and both mitochondrial and chloroplast DNA haplotypes in a natural population of ponderosa pine (Pinus ponderosa, Laws). Three allozyme loci showed significant associations with mtDNA variation, while two other loci showed significant association with cpDNA. However, the absolute number of individuals involved in any of the associations was small, such that in none of the nuclear-organellar combinations was the difference between observed and expected numbers >11 individuals. Patterns of association were not consistent across loci or organellar genomes, suggesting that they are not the result of mating patterns, which would act uniformly on all loci. This pattern of disequilibria is consistent with the action of genetic drift and with existing knowledge of the structure of this population and thus does not imply the action of other evolutionary processes. The overall magnitude (normalized disequilibrium) of associations was greater for maternally inherited mtDNA than for paternally inherited cpDNA, though this difference was neither large nor significant. Such significant disequilibria involving the paternally inherited organelle indicate that not only are there a limited number of seed parents, but the effective number of pollen parents is also limited.     

Molecular genetic and genetic correlations in sodium channelopathies: Lack of founder effect and evidence for a second gene

We present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. We found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, we identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, it fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism–derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations.     

The effect of migratory behaviour on genetic diversity and population divergence: a comparison of anadromous and freshwater Atlantic salmon Salmo salar

The genetic diversity of anadromous and freshwater Atlantic salmon ( Salmo salar ) populations from north-west Russia and other north European locations was compared using microsatellite variation to evaluate the importance of anadromous migration, population size and population glacial history in determining population genetic diversity and divergence. In anadromous Atlantic salmon populations, the level of genetic diversity was significantly higher and the level of population divergence was significantly lower than among the freshwater Atlantic salmon populations, even after correcting for differences in stock size. The phylogeographic origin of the populations also had a significant effect on the genetic diversity characteristics of populations: anadromous populations from the basins of the Atlantic Ocean, White Sea and Barents Sea possessed higher levels of genetic diversity than anadromous populations from the Baltic Sea basin. Among the freshwater populations, the result was the opposite: the Baltic freshwater populations were more variable. The results of this study imply that differences in the level of long-term gene flow between freshwater populations and anadromous populations have led to different levels of genetic diversity, which was also evidenced by the hierarchical analysis of molecular variance. Furthermore, the results emphasize the importance of taking the life history of a population into consideration when developing conservation strategies: due to the limited possibilities for new genetic diversity to be generated via gene flow, it is expected that freshwater Atlantic salmon populations would be more vulnerable to extinction following a population crash. Hence, high conservation status is warranted in order to ensure the long-term survival of the limited number of European populations with this life-history strategy.     

Genetic characterization and founder effect analysis of recently introduced Salers cattle breed population

Salers are a native French breed used for beef and dairy production that has expanded to all the continents. The Salers breed was introduced to the north of Spain in 1985 with only 15 individuals from France and has successfully increased to over 20 000 animals. Although over time new animals have been imported from France for breeding, it is possible that the limiting number of founder animals could have resulted in a reduction of the genetic diversity found in Spanish Salers. Thus, the purpose of the present study has been to characterize the genetic diversity of Salers breed in Spain and evaluate a possible founder effect due to reduced number of the first reproducers. A total of 403 individuals from 12 Salers herds were analyzed using 12 microsatellite markers and compared with phylogenetically and geographically close related Blonde d’Aquitaine, Limousin and Charolais French breeds but also other 16 European breeds. Microsatellites in Salers were polymorphic, with a mean allelic richness of 5.129 and an expected heterozygosity of 0.621 across loci (0.576 to 0.736 among all breeds). Average observed heterozygosity was 0.618. All the loci fit the Hardy–Weinberg (HW) equilibrium except TGLA227 locus due to a significant deficit of heterozygotes in only one of the herds, probably attributable to a sampling effect. When all loci were combined, Salers inbreeding coefficient did not differ statistically from 0 (F_IS=0.005), indicating not significant excess or deficit of heterozygotes (P=0.309). Based in allelic distribution, Salers revealed a frequency of 0.488 in BM2113-131 and 0.064 in BM2113-143 diagnostic alleles, which are specific to the African zebu. These zebu alleles are also found in some French breeds, supported by STR data previously postulated hypothesis of a migration route through Mediterranean route by which North African cattle may have left a genetic signature in southern Europe. Phylogenetic tree and population structure analyses could unambiguously differentiate Salers cattle from the other populations and 10% of the total genetic variability could be attributed to differences among breeds (mean R_ST=0.105; P<0.01). Mutation-drift equilibrium tests (sign test and Wilcoxon’s sign rank test) were in correspondence to the absence of founder effect when Bonferroni was applied. Gene diversity previously reported in French Salers was comparable with the observed in our population. Thus, high genetic diversity in Spanish Salers highlights the resources of this population, which looks toward future breeding and selection programs.