Negative‐assortative mating for color in wolves

There is strong negative‐assortative mating for gray and black pelage color in the iconic wolves in Yellowstone National Park. This is the first documented case of significant negative‐assortative mating in mammals and one of only a very few cases in vertebrates. Of 261 matings documented from 1995 to 2015, 63.6% were between gray and black wolves and the correlation between mates for color was –0.266. There was a similar excess of matings of both gray males × black females and black males × gray females. Using the observed frequency of negative‐assortative mating in a model with both random and negative‐assortative mating, the estimated proportion of negative‐assortative mating was 0.430. The estimated frequency of black wolves in the population from 1996 to 2014 was 0.452 and these frequencies appear stable over this 19‐year period. Using the estimated level of negative‐assortative mating, the predicted equilibrium frequency of the dominant allele was 0.278, very close to the mean value of 0.253 observed. In addition, the patterns of genotype frequencies, that is, the observed proportion of black homozygotes and the observed excess of black heterozygotes, are consistent with negative‐assortative mating. Importantly these results demonstrate that negative‐assortative mating could be entirely responsible for the maintenance of this well‐known color polymorphism.     

Detection of major gene for Gilles de la Tourette syndrome

The families of 250 consecutive, unselected patients with Tourette syndrome (TS) were analyzed. If the parents had either motor or vocal tics, but not both, there was an increased risk of both TS and tics in the offspring. The mode of inheritance of the combined tic-Tourette trait was evaluated in both nuclear families and extended pedigrees. Complex segregation analysis was carried out allowing for possible contributions from both a major autosomal locus and multifactorial inheritance of variation in the background of each genotype. The most likely mode of inheritance was a major semidominant gene, Ts, with low heritability of the multifactorial background variation. This was true regardless of assumptions about the prevalence of the disorder. The hypothesis of strict multifactorial inheritance could not be rejected with nuclear family data alone. However, the hypothesis of no major gene effect was rejected using data on 3 generations for any estimate of lifetime risk less than 12 per 1,000 in the general population. A pure recessive major gene effect was also rejected. With a gene frequency of approximately .5%, the penetrance was estimated to be about 94% in abnormal Ts/Ts homozygotes, 50% in Ts/ts heterozygotes, and less than 0.3% in normal ts/ts homozygotes. More than two of every three cases are heterozygotes, and nearly all other cases are phenocopies or new mutations. This is the first demonstration by segregation analysis of a major gene in a human neuropsychiatric disorder with a frequency approaching 1% of the population.     

Frequency-dependent selection and the evolution of assortative mating

A long-standing goal in evolutionary biology is to identify the conditions that promote the evolution of reproductive isolation and speciation. The factors promoting sympatric speciation have been of particular interest, both because it is notoriously difficult to prove empirically and because theoretical models have generated conflicting results, depending on the assumptions made. Here, we analyze the conditions under which selection favors the evolution of assortative mating, thereby reducing gene flow between sympatric groups, using a general model of selection, which allows fitness to be frequency dependent. Our analytical results are based on a two-locus diploid model, with one locus altering the trait under selection and the other locus controlling the strength of assortment (a "one-allele" model). Examining both equilibrium and nonequilibrium scenarios, we demonstrate that whenever heterozygotes are less fit, on average, than homozygotes at the trait locus, indirect selection for assortative mating is generated. While costs of assortative mating hinder the evolution of reproductive isolation, they do not prevent it unless they are sufficiently great. Assortative mating that arises because individuals mate within groups (formed in time or space) is most conducive to the evolution of complete assortative mating from random mating. Assortative mating based on female preferences is more restrictive, because the resulting sexual selection can lead to loss of the trait polymorphism and cause the relative fitness of heterozygotes to rise above homozygotes, eliminating the force favoring assortment. When assortative mating is already prevalent, however, sexual selection can itself cause low heterozygous fitness, promoting the evolution of complete reproductive isolation (akin to "reinforcement") regardless of the form of natural selection.     

The effect of positive assortative mating at one locus on a second linked locus

Summary A model for positive assortative mating based on genotype for one locus is employed to investigate the effect of this mating system on the genotypic structure of a second linked locus as well as on the joint genotypic structure of these two loci. It is shown that the second locus does not attain a precise positive assortative mating structure, but yet it shares a property that is characteristic of positive assortative mating, namely an increase in the frequency of homozygotes over that typically found in panmictic structures. Given any arbitrary genotypic structure for the parental population, the resulting offspring generation possesses a structure at the second locus that does not depend on the recombination frequency, while the joint structure of course does. In case assortative mating as well as linkage are not complete, there exists a unique joint equilibrium state for the two loci, which is characterized by complete stochastic independence between the two loci as well as by Hardy-Weinberg proportions at the second locus. For the second locus alone, Hardy-Weinberg equilibrium is realized if and only if gametic linkage equilibrium and an additionally specified condition are realized.     

Testing mate choice and overdominance at MH in natural families of Atlantic salmon Salmo salar

This study aimed to test mate choice and selection during early life stages on major histocompatibility (MH) genotype in natural families of Atlantic salmon Salmo salar spawners and juveniles, using nine microsatellites to reconstruct families, one microsatellite linked to an MH class I gene and one minisatellite linked to an MH class II gene. MH‐based mate choice was only detected for the class I locus on the first year, with lower expected heterozygosity in the offspring of actually mated pairs than predicted under random mating. The genotype frequencies of MH‐linked loci observed in the juveniles were compared with frequencies expected from Mendelian inheritance of parental alleles to detect selection during early life stages. No selection was detected on the locus linked to class I gene. For the locus linked to class II gene, observed heterozygosity was higher than expected in the first year and lower in the second year, suggesting overdominance and underdominance, respectively. Within family, juveniles' body size was linked to heterozygosity at the same locus, with longer heterozygotes in the first year and longer homozygotes in the second year. Selection therefore seems to differ from one locus to the other and from year to year.     

In Candida albicans,white-opaque switchers are homozygous for mating type

The relationship between the configuration of the mating type locus (MTL) and white-opaque switching in Candida albicans has been examined. Seven genetically unrelated clinical isolates selected for their capacity to undergo the white-opaque transition all proved to be homozygous at the MTL locus, either MTLa or MTLalpha. In an analysis of the allelism of 220 clinical isolates representing the five major clades of C. albicans, 3.2% were homozygous and 96.8% were heterozygous at the MTL locus. Of the seven identified MTL homozygotes, five underwent the white-opaque transition. Of 20 randomly selected MTL heterozygotes, 18 did not undergo the white-opaque transition. The two that did were found to become MTL homozygous at very high frequency before undergoing white-opaque switching. Our results demonstrate that only MTL homozygotes undergo the white-opaque transition, that MTL heterozygotes that become homozygous at high frequency exist, and that the generation of MTL homozygotes and the white-opaque transition occur in isolates in different genetic clades of C. albicans. Our results demonstrate that mating-competent strains of C. albicans exist naturally in patient populations and suggest that mating may play a role in the genesis of diversity in this pernicious fungal pathogen.     

Estimating null allele frequencies at a microsatellite locus in the oystercatcher (Haematopus ostralegus)

A significant heterozygote deficiency was found for microsatellite locus 20H7 among adult breeding birds in four populations of the oystercatcher ( Haematopus ostralegus ). Genotype frequencies at seven other loci were according to Hardy–Weinberg equilibria. Deviations between observed and expected genotype numbers decreased substantially when the data were corrected based on the estimated frequency of a putative null allele at locus 20H7 . However, no null homozygotes were observed in the total sample of 378 individuals. The probability that, because of chance effects, null homozygotes were not represented in the sample ( n =230) from the most intensively studied population (Schiermonnikoog) was estimated to be less than 1%. Parent–offspring comparisons from Schiermonnikoog showed that observed genotype numbers in the offspring were in accordance with expected values based on the estimated frequency of the putative null allele in the population. Moreover, a null homozygote was observed among the nestlings. The combined results indicated that a null allele is present at locus 20H7 in oystercatchers and that the inheritance is according to normal Mendelian segregation. If the absence of null homozygotes among adult animals cannot be ascribed to statistical effects, null homozygotes may suffer a selective disadvantage during the juvenile stage.     

Effects of a Locus Affecting Floral Pigmentation in Ipomoea Purpurea on Female Fitness Components

A locus influencing floral pigment intensity in the morning glory, Ipomoea purpurea, is polymorphic throughout the southeastern United States. Previous work has suggested that the white allele at this locus has a transmission advantage during mating because of the effect of flower color on pollinator behavior. The experiment described here was designed to determine whether other effects of the W locus may contribute an opposing selective advantage to the dark allele. Dark homozygotes were vegetatively smaller and produced fewer flowers, seed capsules and seeds than either light heterozygotes or white homozygotes. In addition, dark homozygotes produced smaller seeds than heterozygotes, and there is some indication that white homozygotes also produced smaller seeds than heterozygotes. Pleiotropic effects on seed number thus do not seem to contribute to selection opposing the mating advantage associated with the white allele. However, pleiotropic effects on seed size might contribute to overdominance that could stabilize the W locus polymorphism.     

Effect of genetic heterogeneity and assortative mating on linkage analysis: a simulation study.

Linkage studies of complex genetic traits raise questions about the effects of genetic heterogeneity and assortative mating on linkage analysis. To further understand these problems, I have simulated and analyzed family data for a complex genetic disease in which disease phenotype is determined by two unlinked disease loci. Two models were studied, a two-locus threshold model and a two-locus heterogeneity model. Information was generated for a marker locus linked to one of the disease-defining loci. Random-mating and assortative-mating samples were generated. Linkage analysis was then carried out by use of standard methods, under the assumptions of a single-locus disease trait and a random-mating population. Results were compared with those from analysis of a single-locus homogeneous trait in samples with the same levels of assortative mating as those considered for the two-locus traits. The results show that (1) introduction of assortative mating does not, in itself, markedly affect the estimate of the recombination fraction; (2) the power of the analysis, reflected in the LOD scores, is somewhat lower with assortative rather than random mating. Loss of power is greater with increasing levels of assortative mating; and (3) for a heterogeneous genetic disease, regardless of mating type, heterogeneity analysis permits more accurate estimate of the recombination fraction but may be of limited use in distinguishing which families belong to each homogeneous subset. These simulations also confirmed earlier observations that linkage to a disease "locus" can be detected even if the disease is incorrectly defined as a single-locus (homogeneous) trait, although the estimated recombination fraction will be significantly greater than the true recombination fraction between the linked disease-defining locus and the marker locus.     

Predicting genotypes at loci for autosomal recessive disorders using linked genetic markers: application to Wilson's disease

Summary Recently, the Wilson's disease locus (WND) has been mapped to the long arm of chromosome 13. We have analyzed segregation of serveral chromosome 13 markers flanking the WND locus and used multipoint linkage analysis to determine the most likely WND genotype of each of 57 unaffected individuals in 5 Wilson's disease families. Approximately 46% of these could be classified as carrier (heterozygote), homozygous normal, or homozygous affected (not yet symptomatic) with a probability of at least 90%, while 77% could be classified with a probability of at least 80%. Our results demonstrate that even though there is a significant decrease on average in serum copper concentration in Wilson's disease heterozygotes compared to normal homozygotes, other sources of variation in serum copper concentration are much greater and preclude use of serum copper to detect heterozygotes for Wilson's disease. Subsequent analyses showed that a familial component, independent of WND genotype, is the major factor accounting for variation in ceruloplasmin levels among unaffected individuals; age is another factor accounting for more variation in copper levels among unaffected individuals than WND genotype.     

Do malaria parasites mate non-randomly in the mosquito midgut?

Polymerase chain reaction (PCR)-based genotyping of oocysts dissected from mosquito midguts has previously been used to investigate overall levels of inbreeding within malaria parasite populations. We present a re-analysis of the population structure of Plasmodium falciparum malaria using diploid genotypes at three antigen-encoding loci in 118 oocysts dissected from 34 mosquitoes. We use these data to ask whether mating is occurring at random within the mosquito midgut, as is generally assumed. We observe a highly significant deficit of heterozygous oocysts within mosquitoes at all three loci, suggesting that fusion of gametes occurs non-randomly in the mosquito gut. A variety of biological explanations, such as interrupted feeding of mosquitoes, positive assortative mating and outcrossing depression, could account for this observation. However, an alternative artefactual explanation--the presence of non-amplifying or null alleles--can account for the observed data equally well, without the need to invoke non-random mating. To evaluate this explanation further, we estimate the frequencies of null alleles within the oocyst population using maximum likelihood, by making the assumption that non-amplifying oocysts at any of the three loci are homozygous for null alleles. Observed levels of visible heterozygotes fit closely with those expected under random mating when non-amplifying oocysts are accounted for. Other lines of evidence also support the artefactual explanation. Overall inbreeding coefficients have been recalculated in the light of this analysis, and may be considerably lower than those estimated previously. In conclusion, we suggest that the deficit of heterozygotes observed is unlikely to indicate non-random mating within the mosquito gut and is better explained by misscoring of heterozygotes as homozygotes.     

Tss (Tail-short Shionogi), a new short tail mutation found in the BALB/cMs strain, maps quite closely to the Tail-short (Ts) locus on mouse chromosome 11.

A spontaneous morphological mutation characterized by a short and kinky tail (Tail-short Shionogi: Tss) was observed in a BALB/cMs mouse breeding colony. The inheritance mode of the Tss mutation is semi-dominant, and homozygotes (Tss/Tss) are probably embryonic lethal. The viability of the Tss/+ heterozygotes appear to be influenced by the mating partner: 47.1% of the (BALB/cMs-Tss/+ x C57BL/6J)F1 embryos were the mutant phenotype, whereas there were no (BALB/cMs-Tss/+ x A/J)F1 embryos with the mutant phenotype. The Tss locus was mapped by linkage analysis between microsatellite markers D11Mit128 and D11Mit256 on mouse Chromosome 11. These results suggest that the Tss mutation is a new allele on the Tail-short (Ts) locus.     

Electrophoretic evidence for disomic inheritance and allopolyploid origin of the octoploid Cerastium alpinum (Caryophyllaceae)

The mode of inheritance of six enzyme markers in the octoploid alpine plant Cerastium alpinum was analyzed. Offspring from crosses between heterozygotes showed fixed heterozygosity at malate dehydrogenase-2, phosphoglucoisomerase-2, triosephosphate isomerase-2, and triosephosphate isomerase-3. Phosphoglucomutase-1 also showed fixed heterozygosity except in offspring from one cross. Fixed heterozygosity in five enzyme systems suggests that C. alpinum has originated through at least some allopolyploidization. Offspring from plants heterozygous for two alleles at the menadione reductase-1 (Mr-1) locus did not deviate significantly from a 1:2:1 ratio. The large proportion of homozygotes suggests disomic inheritance because any kind of polysomic inheritance would result in a substantially increased proportion of heterozygotes relative to disomic inheritance. Assuming a diploid model for Mr-1, this locus was used to analyze the population genetic structure within C. alpinum populations. Inbreeding was found in many alpine populations. This may help explain the large genetic distances found among alpine populations in a previous study. The analysis is only based on one segregating locus, and the results should therefore be treated with caution. However, by establishing the mode of inheritance through crosses, we have been able to use a codominant marker in population genetic analysis of an octoploid plant.     

EVOLUTION OF DOMINANCE UNDER FREQUENCY-DEPENDENT INTRASPECIFIC COMPETITION IN AN ASSORTATIVELY MATING POPULATION

We study the evolution of higher levels of dominance as a response to negative frequency-dependent selection. In contrast to previous studies, we focus on the effect of assortative mating on the evolution of dominance under frequency-dependent intraspecific competition. We analyze a two-locus two-allele model, in which the primary locus has a major effect on a quantitative trait that is under a mixture of frequency-independent stabilizing selection, density-dependent selection, and frequency-dependent selection caused by intraspecific competition for a continuum of resources. The second (modifier) locus determines the degree of dominance at the trait level. Additionally, the population mates assortatively with respect to similarities in the ecological trait. Our analysis shows that the parameter region in which dominance can be established decreases if small levels of assortment are introduced. In addition, the degree of dominance that can be established also decreases. In contrast, if assortment is intermediate, sexual selection for extreme types can be established, which leads to evolution of higher levels of dominance than under random mating. For modifiers with large effects, intermediate levels of assortative mating are most favorable for the evolution of dominance. For large modifiers, the speed of fixation can even be higher for intermediate levels of assortative mating than for random mating.     

Analysis of partial assortative mating and sexual selection models for a polygamous species involving a trait based on levels of heterozygosity

The consequences of preferential mating in the presence of partial assortative and sexual selection mechanisms are ascertained for a two-allele one-locus trait involving two phenotype classes C₁ = {all homozygotes} and C₂ = {heterozygotes}. Relevant biological cases may include Burley (1977, Proc. Nat. Acad. Sci. USA74, 3476–3479), Wilbur et al. (1978, Evolution32, 264–270), and Singh and Zouros (1978, Evolution32, 342–353). When the preference rate for the heterozygote exceeds that for homozygotes, it is established that the unique stable state is the central Hardy-Weinberg equilibrium. The rate of approach is faster with sexual selection than for the corresponding model of assortative mating. When the preference rates favor the homozygotes then in this symmetric model of sexual selection two asymmetric Hardy-Weinberg polymorphisms can evolve, and which succeeds depends on initial conditions. The models are also analyzed with natural selection acting on phenotypes superimposed on assortative mating. In this case we can have up to three coexisting stable states involving both fixation alternatives and a central polymorphism. The corresponding model with sexual selection maintains either the central equilibrium as in assortative mating or two asymmetric polymorphic equilibria.     

REPRODUCTIVE ISOLATION AND LOCAL ADAPTATION QUANTIFIED FOR A CHROMOSOME INVERSION IN A MALARIA MOSQUITO

Chromosome inversions have long been thought to be involved in speciation and local adaptation. We have little quantitative information, however, about the effects that inversion polymorphisms have on reproductive isolation and viability. Here we provide the first estimates from any organism for the total amount of reproductive isolation associated with an inversion segregating in natural populations. We sampled chromosomes from 751 mosquitoes of the malaria vector Anopheles funestus along a 1421 km transect in Cameroon that traverses savannah, highland, and rainforest ecological zones. We then developed a series of population genetic models that account for selection, migration, and assortative mating, and fit the models to the data using likelihood. Results from the best‐fit models suggest there is strong local adaptation, with relative viabilities of homozygotes ranging from 25% to 130% compared to heterozygotes. Viabilities vary qualitatively between regions: the inversion is underdominant in the savannah, whereas in the highlands it is overdominant. The inversion is also implicated in strong assortative mating. In the savannah, the two homozygote forms show 92% reproductive isolation, suggesting that this one inversion can generate most of the genetic barriers needed for speciation.     

The effect of positive assortative mating at one locus on a second linked locus

Summary Considerations proceed from a model of positive assortative mating based on genotype at one locus, with an arbitrary number of alleles, assuming no selection, mutation, or migration, hypothetically infinite population size, and discrete non-overlapping generations. From these conditions, inferences are made about the genotypic structure at a linked locus, as well as about the corresponding 2-locus gametic structure.The following main results are presented: in the course of the generations, the genotypic structure at the second locus and the 2-locus gametic structure always tend to a limit responsive to the initial conditions concerning the joint genotypic structure at the two loci and the degree of assortativity and linkage. A complete, analytical representation of the limits is given. In particular, if assortative mating is only partial and at the same time linkage is not complete, a population is not able to maintain a permanent deviation of the gametic structure from linkage equilibrium, and thus the genotypic structure at the second locus tends to Hardy-Weinberg proportions. On the other hand, if initial linkage disequilibrium is combined with partial assortative mating and complete linkage (or with complete assortative mating and unlinked loci) the population maintains this disequilibrium and thus the genotypic structure at the second locus need not tend to Hardy-Weinberg proportions. It turns out that the conditions not only of complete linkage, but also of unlinked loci together with complete assortativity, imply no change in gametic structure from the initial structure.In order to demonstrate the influence of several parameters on the speed of convergence to and the magnitude of the respective limits, several graphs are included.     

Host–parasite interactions and the evolution of nonrandom mating

Some species mate nonrandomly with respect to alleles underlying immunity. One hypothesis proposes that this is advantageous because nonrandom mating can lead to offspring with superior parasite resistance. We investigate this hypothesis, generalizing previous models in four ways: First, rather than only examining invasibility of modifiers of nonrandom mating, we identify evolutionarily stable strategies. Second, we study coevolution of both haploid and diploid hosts and parasites. Third, we allow for maternal parasite transmission. Fourth, we allow for many alleles at the interaction locus. We find that evolutionarily stable rates of assortative or disassortative mating are usually near zero or one. However, for one case, in which assumptions most closely match the major histocompatibility complex (MHC) system, intermediate rates of disassortative mating can evolve. Across all cases, with haploid hosts, evolution proceeds toward complete disassortative mating, whereas with diploid hosts either assortative or disassortative mating can evolve. Evolution of nonrandom mating is much less affected by the ploidy of parasites. For the MHC case, maternal transmission of parasites, because it creates an advantage to producing offspring that differ from their parents, leads to higher evolutionarily stable rates of disassortative mating. Lastly, with more alleles at the interaction locus, disassortative mating evolves to higher levels.     

Introgressive hybridization as a mechanism for species rescue

Rapid evolution on ecological time scales can play a key role in species responses to environmental change. One dynamic that has the potential to generate the diversity necessary for evolution rapid enough to allow response to sudden environmental shifts is introgressive hybridization. However, if distinct sub-species exist before an environmental shift, mechanisms that impede hybridization, such as assortative mating and hybrid inferiority, are likely to be present. Here we explore the theoretical potential for introgressive hybridization to play a role in response to environmental change. In particular, we incorporate assortative mating, hybrid inferiority, and demographic stochasticity into a two-locus, two-allele population genetic model of two interacting species where one locus identifies the species and the other determines how fitness depends on the changing environment. Simulation results indicate that moderately high values for the strength of assortative mating will allow enough hybridization events to outweigh demographic stochasticity but not so many that continued hybridization outweighs backcrossing and introgression. Successful introgressive hybridization also requires intermediate relative fitness at the allele negatively affected by environmental change such that hybrid survivorship outweighs demographic stochasticity but selection remains strong enough to affect the genetic dynamics. The potential for successful introgression instead of extinction with greater environmental change is larger with monogamous rather than promiscuous mating due to lower stochasticity in mating events. These results suggest species characteristics (e.g., intermediate assortative mating and mating systems with low variation in mating likelihood) which indicate a potential for rapid evolution in response to environmental change via introgressive hybridization.     

Complex segregation analysis of non-myoclonic idiopathic generalized epilepsy in families ascertained from probands affected with idiopathic epilepsy with tonic-clonic seizures in Antioquia,Colombia

In an attempt to identify the possible role of major genes, multifactorial inheritance, and cohort effects in the susceptibility to idiopathic epilepsy with generalized tonic-clonic seizures of the awakening type (GTCS), complex segregation analysis was performed in 196 nuclear families ascertained through affected probands with idiopathic epilepsy with GTCS belonging to the Paisa community of Antioquia (Colombia). Models postulating no transmission, single major locus (dominant and recessive) only, and multifactorial component only, were rejected. Since the codominant single major locus model could not be rejected and models that assign no major locus to transmission, no polygenic component to transmission, and no transmission of the major effect were rejected, complex segregation analysis suggested that a major autosomal codominant allele together with a multifactorial component (mixed model) best explained clustering of idiopathic epilepsy with GTCS in families of the Paisa community. The deficit of transmission of heterozygotes (0.17) is compatible with the existence of epistasis acting on a major gene whose frequency was estimated to be 0.0211. Its transmission variance accounts for 81% of the susceptibility to idiopathic epilepsy with GTCS. The complementary variance (19%) is due to the polygenic component. Received: 19 January 1996 / Revised: 11 March 1996