No evidence for adjustment of maternal investment under alternative mate availability regimes.

Using treatments that mimic high and low availability of reproductive males, it was found that female three-spined sticklebacks Gasterosteus aculeatus, previously shown to adjust their mate choices when male mates were rare, did not alter their reproductive investment strategies. These results suggest that plasticity in investment is perhaps limited by physiological requirements or dependent on relatively extreme mate availability regimes. The probability of becoming reproductive, number of clutches per season (per female), initial clutch size and mass and the timing of reproduction were all independent of the experience a female had with mate availability. This suggests that pre-copulatory plasticity in reproductive strategies may contribute more to variation in the strength and direction of sexual selection than reproductive investment in offspring.

Divergent sexual selection via male competition: ecology is key.

Sexual selection and ecological differences are important drivers of speciation. Much research has focused on female choice, yet the role of male competition in ecological speciation has been understudied. Here, we test how mating habitats impact sexual selection and speciation through male competition. Using limnetic and benthic species of threespine stickleback fish, we find that different mating habitats select differently on male traits through male competition. In mixed habitat with both vegetated and open areas, selection favours two trait combinations of male body size and nuptial colour: large with little colour and small with lots of colour. This matches what we see in reproductively isolated stickleback species, suggesting male competition could promote trait divergence and reproductive isolation. In contrast, when only open habitat exists, selection favours one trait combination, large with lots of colour, which would hinder trait divergence and reproductive isolation. Other behavioural mechanisms in male competition that might promote divergence, such as avoiding aggression with heterospecifics, are insufficient to maintain separate species. This work highlights the importance of mating habitats in male competition for both sexual selection and speciation.

Sequential mate choice and sexual isolation in threespine stickleback species.

Sequential mate choice strategies predict how females should alter their choosiness based on the availability of attractive males. There are many studies on sequential mate choice within species, but few have asked whether females apply these strategies to interactions between species and how these strategies may affect hybridization. We tested how previous interactions with conspecific and heterospecific males affect mate preference and sexual isolation in two threespine stickleback species (benthics and limnetics: Gasterosteus spp.). Consistent with previous work, we found that within species, stickleback females gauge male attractiveness relative to previously encountered males. If females extend these decision rules between species, we predicted that previous interactions with conspecifics should make heterospecifics less attractive, whereas interactions with heterospecifics should make conspecifics more attractive. However, females found heterospecifics less attractive after prior experience, largely independent of the species of male first encountered. Thus, sequential mate choice strategies are used within but not between species in sticklebacks. Further, learning from prior courtship interactions acts to enhance existing sexual isolation between species.

Hybridization and speciation.

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.

Plastic responses to parents and predators lead to divergent shoaling behaviour in sticklebacks.

Population divergence in antipredator defence and behaviour occurs rapidly and repeatedly. Genetic differences, phenotypic plasticity or parental effects may all contribute to divergence, but the relative importance of each of these mechanisms remains unknown. We exposed juveniles to parents and predators to measure how induced changes contribute to shoaling behaviour differences between two threespine stickleback species (benthics and limnetics: Gasterosteus spp). We found that limnetics increased shoaling in response to predator attacks, whereas benthics did not alter their behaviour. Care by limnetic fathers led to increased shoaling in both limnetic and benthic offspring. Shoaling helps limnetics avoid trout and avian predation; our results suggest that this adaptive behaviour is the result of a combination of paternal effects, predator-induced plasticity and genetic differences between species. These results suggest that plasticity substantially contributes to the rapid divergence in shoaling behaviour across the post-Pleistocene radiation of sticklebacks.

Natural selection and parallel speciation in sympatric sticklebacks.

Natural selection plays a fundamental role in most theories of speciation, but empirical evidence from the wild has been lacking. Here the post-Pleistocene radiation of threespine sticklebacks was used to infer natural selection in the origin of species. Populations of sticklebacks that evolved under different ecological conditions show strong reproductive isolation, whereas populations that evolved independently under similar ecological conditions lack isolation. Speciation has proceeded in this adaptive radiation in a repeatable fashion, ultimately as a consequence of adaptation to alternative environments.

Congenital cardiovascular malformations: questions on inheritance. Baltimore-Washington Infant Study Group.

The Baltimore-Washington Infant Study, an epidemiologic investigation of congenital heart disease, searches for genetic and environmental risk factors. Among 2,102 infants with heart disease, 17.5% had a noncardiac abnormality of chromosomal or genetic origin, whereas among 2,328 control infants, only 0.7% had a genetic abnormality. Familial cardiovascular malformations encountered can be grouped into five distinct etiologic mechanisms. Single gene effects may be responsible for the specific histologic and biochemical changes in familial atrial septal defect with conduction disturbance and also in idiopathic ventricular hypertrophy. Left heart lesions showed familial concordance by the presumed morphogenetic mechanism of abnormal embryonic blood flow with phenotypes of varying severity. Pulmonary stenosis appeared with familial heritable disorders, as well as a partially concordant lesion with tetralogy of Fallot. Ventricular septal defect with transposition of the great arteries (one sibling pair) and with truncus arteriosus (two sibling pairs) indicate forme fruste expression of conotruncal defects. Endocardial cushion defect occurred with and without Down's syndrome in members of three families, suggesting inheritance of a defect affecting cellular migration. Heritable blood coagulopathies occurred in case families and not in control families. The associated of hemophilia and transposition, observed also by others, is extremely unlikely by chance and suggests genetic errors of endothelial cell function. The description of specific families from a population-based study emphasizes biologic questions on the nature of the inheritance of cardiovascular malformations.

Vocal learning by greater spear-nosed bats.

Vocal learning is well known among passerine and psittacine birds, but most data on mammals are equivocal. Specific benefits of vocal learning are poorly understood for most species. One case where vocal learning should be favoured by selection is where calls indicate group membership and group mates are unrelated. Female greater spear-nosed bats, Phyllostomus hastatus, live in stable groups of unrelated bats and use loud, broadband calls to coordinate foraging movements of social group mates. Bats benefit from group foraging. Calls differ between female social groups and cave colonies, and playback experiments demonstrate that bats perceive these acoustic differences. Here I show that the group distinctive structure of calls arises through vocal learning. Females change call structure when group composition changes, resulting in increased similarity among new social group mates. Comparisons of transfers with age-matched half-sibs indicate that call changes are not simply due to maturation, the physical environment or heredity. These results suggest that studies testing vocal learning in mammals could profit by focusing on vocalizations that signify group membership.

Assessment of clinical variables and counseling needs in patients with retinitis pigmentosa.

Many medical and personal factors must be considered when attempting to provide comprehensive genetic counseling to families with retinitis pigmentosa (RP). Adequate diagnostic evaluation, the initial step in the counseling process, is not always readily obtained. Prognosis is difficult to assess, and genetic type may be impossible to establish in certain pedigrees. A nationwide questionnaire survey of 899 probands with RP and allied disorders was conducted, and generated data on the patient's perceptions of the clinical aspects of the disease, family history, and the understanding of the disorder by affected persons and their relatives. This study emphasizes the clinical variability of RP and summarizes differences in age of onset of the different genetic types. Clearly, patients must be evaluated extensively and carefully to diagnose retinitis pigmentosa accurately. The extent and limitations of the diagnostic evaluation should be clearly understood by the counselor because some patients with sporadic phenocopies may be diagnosed as having retinitis pigmentosa. Counseling about prognosis should include information regarding the great variation among and within inheritance groups, families, and individuals with respect to age of onset and natural history of the disorder. All patients should be considered for hearing evaluations since as many as 30% of RP patients may have hearing impairments. Because no treatment is currently available for most RP patients, genetic counseling and supportive follow-up should be viewed as an essential service for this common group of genetic disorders, and co-operation with the ophthalmologic diagnostician should be actively sought.

Problems in detecting etiological heterogeneity in genetic disease illustrated with retinitis pigmentosa.

Simulated data were generated under four etiologic mechanisms for each of 20 different pedigree structures drawn from a study of families ascertained through a proband with retinitis pigmentosa. These simulated data were then used to identify subgroups of pedigrees which best supported each of three genetic mechanisms (autosomal dominant, autosomal recessive, X-linked recessive with 10% penetrance of disease in heterozygous females) and a non-genetic, sporadic mechanism. Results of these studies show that pedigrees identified as supporting one genetic model in a 'model choice' approach tend to be etiologically homogeneous, but are not truly representative of all the phenotypic combinations possible under that mechanism. The problem of etiologic heterogeneity is most acute when dealing with pedigrees less than size 10. Pedigrees lumped under a non-genetic, sporadic mechanism are extremely heterogeneous and studies of the natural history of diseases where both genetic and non-genetic mechanisms may be operating (such as with retinitis pigmentosa) should avoid using this group of largely simplex pedigrees.

Pentalogy of Cantrell and associated midline anomalies: a possible ventral midline developmental field.

Five cases of the Pentalogy of Cantrell (PC), ascertained through the Baltimore-Washington population-based study of infants with congenital cardiovascular malformations, represent a regional prevalence of 5.5/1 million liveborn infants for this disorder. Three of these patients had cleft lip with or without palate. Review of the reported literature of the Pentalogy of Cantrell and various combinations of the anomalies within the spectrum of this pentad suggests that the PC defines a specific midline ventral developmental field. Cleft lip with or without cleft palate and encephalocele tend to specifically associate with ventral midline anomalies within the spectrum of PC. These associations might either illustrate the previously observed tendency of specific occurrence of certain combinations of midline defects or represent defined subunits of the midline developmental field.

Endocardial cushion defect: further studies of "isolated" versus "syndromic" occurrence.

The isolated occurrence of endocardial cushion defect (ECD) has been suggested to differ from its occurrence within the context of a syndrome, with regard to the nature (complete or partial) of the defect and the associated cardiovascular malformations. Analysis of data derived from the Baltimore-Washington Infant Study of congenital cardiovascular malformations supports the observation that "syndromic" ECD tends to be of the complete atrioventricular canal type and is less frequently associated with left cardiac anomalies than the isolated form. However, each syndrome has a unique impact on the overall cardiovascular "phenotype", including the ECD. This is especially true for Down and Ivemark syndromes, which are most frequently associated with ECD, but also for other syndromes as well. It is also suggested that isolated ECD is specifically associated with gastrointestinal and urinary tract anomalies. However, in Down syndrome ECD appears to be a specific cardiovascular expression of the trisomic state that is unrelated to other noncardiac malformations. Additional information on the association of ECD with other less common genetic syndromes is needed in order to further investigate the possible genetic basis of this cardiac defect.

Segregation distortion in inheritance of progressive rod cone degeneration (prcd) in miniature poodle dogs.

Segregation distortion was observed in inheritance of progressive rod-cone degeneration (prcd) in a colony of Miniature Poodle dogs. Breeding results, from both retrospective records and prospectively planned matings, were classified into five mating types: (1) affected to affected, (2) homozygous normal sire to any dam, (3) heterozygous to heterozygous, (4) heterozygous sire to affected dam, and (5) affected sire to heterozygous dam. For all but the last category, results were in accord with mendelian expectations for autosomal-recessive inheritance. However, litters of mating type 5 had fewer affected pups (20/77) than expected. The observed segregation ratio for this mating type (0.26) was significantly (P less than 0.001) less than the expected (0.50). The segregation distortion could not be accounted for by either pre- or postnatal loss of affected pups, as litter size and litter survivability were uniform among litters of different mating types. Either the prcd locus, or a linked locus, would appear to influence either gametic or zygotic fitness in the heterozygous mother. Comparison is drawn to the inheritance of retinitis pigmentosa in humans, in which decreased segregation ratios are also recognized.

Gonadal (ovarian) dysgenesis in 46,XX individuals: frequency of the autosomal recessive form.

Gonadal (ovarian) dysgenesis with normal chromosomes (46,XX) clearly is a heterogeneous condition. In some forms, the defect is restricted to the gonads, whereas other affected females show neurosensory hearing loss (Perrault syndrome). In another form, brothers may have germ cell aplasia [Granat et al., Fertil Steril 1983; 40:215-219]. Nongenetic causes exist as well. To elucidate the proportion of XX gonadal (ovarian) dysgenesis due to autosomal recessive genes, we analyzed published (N = 17) and unpublished (N = 8) families having at least two female offspring. Analysis was restricted to cases in whom ovarian failure was documented by the presence of streak ovaries (published cases) or elevated gonadotropins (unpublished cases). We reasoned that the closer to that segregation ratio expected for an autosomal recessive trait (0.25), the lower the frequency of nongenetic forms. Segregation analysis utilized standard correction for single ascertainment, with only females included in the preliminary analysis. The segregation ratio estimate was 0.16. Our results suggest that many 46,XX females with gonadal (ovarian) dysgenesis represent a disorder segregating as an autosomal recessive trait, placing sisters of these cases at a 25% risk for this disorder.

Familial risks of congenital heart defect assessed in a population-based epidemiologic study.

Congenital heart defects (CHD) represent a heterogeneous group of disorders caused by chromosome abnormalities, mendelian disorders, teratogenic exposures, and unknown etiologic mechanisms. A large group of various isolated defects is presumably multifactorial in origin. Previous studies of familial risks for specific anatomic defects obtained from clinical series may include significant biases and obscured pathogenic relationships. In this population-based study we analyzed all cases of CHD in infants and a control birth cohort in the Baltimore-Washington area. The rates of CHD were defined for first-degree relatives of cases with isolated defects, grouped by a pathogenic classification scheme. Precurrence risks were found to vary among the groups, and risks for flow lesions were higher than previously reported. The sibling precurrence risk for hypoplastic left heart syndrome (13.5%) was not significantly different from that expected for an autosomal recessive mechanism; the risks for different types of ventricular septal defects (VSD) varied among mechanistic groups. The results indicate that the additive multifactorial model does not adequately account for the risks in all forms of isolated CHD of unknown etiology.

Genetic epidemiologic study of hearing loss in an adult population.

Previous population studies of hearing loss have been limited to children with moderate to profound impairment, and have reported that heritability accounts for at least 50% of congenital or early-onset cases. The present study was designed to assess genetic factors associated with late-onset hearing impairment in an adult population. A brief family history and audiologic questionnaire was sent to approximately 11,200 members of the consumer organization, Self Help for the Hard of Hearing, Inc., and 4,039 questionnaires were returned. All respondents reported having at least one previous audiologic exam. Reported data were verified against audiograms when available. Regardless of the reported causes, 49% of early-onset cases (< or = 20 years of age) had one or two parent(s) with some form of hearing loss compared with 62% in later-onset cases. As expected, mean age at onset was substantially younger for cases with positive family histories than cases with negative family histories. Results from nuclear segregation analysis showed that fully recessive and dominant models failed to explain the early- or late-onset hearing loss data. In this nationwide survey, the large proportion of cases with positive family histories clearly indicates the importance of genetic factors in adult-onset forms of hearing loss. Comparison with younger-onset cases will permit further delineation of differences in inheritance patterns. This study should identify more homogeneous groups of adult-onset families for further genetic study, and provide empiric information for use in genetic counselling.

Lack of an association between diffuse systemic sclerosis and HLA-DR1 or HLA-DR5.

The HLA-DR locus of the major histocompatibility complex encodes class II molecules which participate in immune responses through regulation of T cell interaction with antigen presenting cells. Previous association studies between HLA-DR antigens and the autoimmune disease, systemic sclerosis (or scleroderma), have yielded conflicting results. Some investigators have reported an association between this disease and HLA-DR1, while others have demonstrated an association with HLA-DR5. In this study, we used restriction fragment length polymorphisms in the HLA-DR locus to compare allelic frequencies of HLA-DR1 and HLA-DR5 in scleroderma patients with diffuse disease and healthy control subjects. No significant difference in the allelic frequency of either antigen was observed between the groups. These results suggest that HLA-DR1 and HLA-DR5 antigens are unlikely to contribute significantly to disease susceptibility in scleroderma.

Accuracy of detection of the retinoblastoma gene by esterase D linkage.

The gene for hereditary retinoblastoma (Rb), an autosomal dominant trait localized to the long arm of chromosome 13, is linked to the locus for the enzyme esterase D (EsD). We analyzed a three-generation family that demonstrates cosegregation of alleles at the EsD locus and the Rb locus. This kindred yields a logarithm of the odds ratio (LOD) score of 2.46 at a recombination fraction (0) of 0.0. When combined with five other recently reported families, the resulting maximum score was 11.08 at 0 = 0.0. This combined LOD score and the lack of demonstrable crossovers in more than 65 individuals indicate that predictions of the Rb gene carrier state based on EsD genotyping are at least 90% accurate.

Chemical clastogenicity in lymphoid cell lines of chromosomal instability syndromes.

Long-term lymphoid cell lines (LCL) derived from normal individuals, patients with ataxia telangiectasia (A-T), xeroderma pigmentosum (XP), and Fanconi anemia (FA) were exposed to various concentrations of 11 chemical clastogens. The agents were chosen to represent a variety of suggested modes of action. In contrast to all other genotypes, the FA lines demonstrated significant rates of spontaneous chromosomal breakage and showed hypersensitivity to all of the clastogens employed. Variability among lines within a genotype suggested individual responses to specific agents. Computation of "corrected values" to address the problem of baseline disparity removed some of the significant differences between the FA and other lines. Nonetheless, following correction, the FA genotype was still delineated by clastogens which are not DNA cross-linkers. The A-T lines were specifically identified by the induction of chromosome damage by bleomycin and neocarzinostatin.

A genetic analysis of retinitis pigmentosa.

Genetic analysis of 457 patients with retinitis pigmentosa (RP) included categorisation of families by recognised mendelian pattern of inheritance and formal segregation analysis of all informative sibships. Of the 368 probands a surprisingly high 18% (68) had significant congenital loss of hearing and were diagnosed as having Usher syndrome. The RP probands were categorised as: 21.7% autosomal dominant, 9.0% X-linked, 16.0% autosomal recessive, 3.3% genetic type uncertain, and 50.0% simplex. Segregation analysis reflected this high proportion of simplex cases, accounting for reduced penetrance in dominant families; only 20% remain classified as sporadic (possibly nongenetic). In the matings between normal persons estimates of the segregation ratio also indicate lower values than expected. Unlike in RP sibship, segregation in the Usher syndrome is consistent with the hypothesis of recessive inheritance. Therefore RP with significant hearing loss segregates as expected, while even if a proband is classified as a dominant or recessive the recurrence risk for the RP phenotype may be below mendelian expectation.