Non-random patterns of non-disjunctional orientation in trivalents of multiple Robertsonian heterozygotes of Dichroplus pratensis (Acrididae)

Metaphase I orientation of centric fusion trivalents was studied in 24 single, 19 double and 3 triple heterozygotes of Dichroplus pratensis. Different populations of this South American melanopline grasshopper are polymorphic for seven Robertsonian fusions, and the polymorphisms seem to be stable. Several cytogenetic factors involved in the orientation and segregation of the meiotic configurations such as chromosomal length, symmetry and number and position of chiasmata, have been analysed in previous works. In this paper we study another factor that is relevant in the above respect in individuals with more than one heterozygous fusion: interaction among configurations regarding orientation.Our results indicate that, when there are two or three trivalents present in the MI cell, there is an interaction in such a way that the number of metaphases in which the two or three trivalents are non-disjunctionally oriented is always significantly higher than expected under a hypothesis of independence. However, the number of cells in which all trivalents are disjunctionally oriented does not decrease significantly, so an increase of unbalanced gametes due to this factor is not expected. The stability of the polymorphisms would thus not be affected.Both authors are affiliated with the CONICET (Argentina)     

Orientation and segregation of Robertsonian trivalents in Dichroplus pratensis (Acrididae)

Pairing behavior, metaphase I orientation, and anaphase I segregation of centric fusion trivalents were studied in 26 single, 15 double, and 2 triple male fusion heterozygotes of the polymorphic South American melanopline grasshopper Dichroplus pratensis. They represent the seven different fusions and their combinations already described in different populations of the species. Our analysis showed the following: (1) pairing behavior is very regular in all trivalents; (2) frequencies of linear orientation was very low irrespective of the trivalent involved; (3) reorientation seems to occur frequently since frequencies of abnormal segregation and aneuploid second division cells were invariably lower than those of nonconvergent orientation; (4) aneuploidy and abnormal sperm production increases with increasing number of fusions; (5) chiasma frequency and localisation is relevant to trivalent orientation since trivalents with nonconvergent orientations showed proximal and interstitial chiasmata more frequently than convergently oriented ones. The results are in agreement with the hypothesis that these polymorphisms are old and stable, and confirm that for the maintenance of a balanced polymorphism, if this polymorphism is adaptive because of its consequences on recombination, position effects, etc., changes tending to stabilise trivalent orientation and segregation are central.     

Population cytology of Oedaleonotus

The grasshopper Oedaleonotus enigma possesses a neo-XY sex system and the rest of the chromosome complement is highly polymorphic, suggesting recent chromosomal evolution. It contains a fusion between two telocentrics, a centric shift and an extra heterochromatic segment, all of which are polymorphic, and in addition it has B-chromosomes. The fusion polymorphism has a preponderance of heterokaryotypes, and despite frequent inbreeding the other two polymorphisms have binomial frequencies of heterokaryotypes. Male individuals with two neo-X chromosomes and no neo-Y (at least in the germ line) are discussed.     

Inheritance and meiotic behaviour of a de novo chromosome fusion in the aphid Myzus persicae (Sulzer)

A de novo tandem fusion between autosomes 2 and 3 (A2+3), arising in the course of laboratory crosses of sexual morphs of two clones of the aphid Myzus persicae, was stable through more than 180 generations of parthenogenetic (clonal) reproduction. Studies of its inheritance through the sexual phase, and segregation from an amplified esterase marker gene, showed that crossing over occurred during oogenesis, but not in spermatogenesis, confirming previous cytological observations. Only a small number of progeny resulted from attempts at selfing fusion heterozygotes, and none of these was homozygous for the fusion. A2+3 paired in parallel alignment with the separate A2 and A3 to form a trivalent at prophase I of spermatogenesis. Fusion heterozygotes had a segregation problem at anaphase I of meiosis, A2+3 forming a chromatin bridge between the daughter spermatocytes in about 42% of dividing cells, which could be attributed to alternate orientation in the trivalent (A2 and A3 paired with opposite sides of A2+3) in the preceding metaphase I. Males heterozygous for an A2 dissociation were also studied and found to have much less of a segregation problem, despite showing similar orientation patterns at metaphase I. Possible reasons for this difference and the significance of the findings in relation to karyotype evolution in aphids are discussed.     

Association of the HindIII Polymorphism of the Lipoprotein Lipase Gene with Myocardial Infarction and the Life Span in Elderly Patients with Coronary Heart Disease

Allele and genotype frequencies of the HindIII polymorphism of the lipoprotein lipase (LPL) gene were studied in patients with myocardial infarction (MI) and stable angina of effort (SAE), including long-lived people (over 90). The polymorphism proved to be associated with MI and with the life span, genotype H+/H+ being predisposing to MI and allele H– being protective. The allele and genotype frequencies of long-lived people differed significantly from the Hardy–Weinberg proportions and from those of SAE patients aged up to 90. An excess of heterozygotes in this group suggests a selective pressure which eliminates homozygotes. Possibly, heterozygotes H+/H– have an adaptive advantage, which provides for their longevity.     

Meiosis and speciation: A study in a speciatingMus terricolor complex

The three chromosomal species of theMus terricolor complex possess 2n = 40 chromosomes. We show that their karyotypes differ in stable heterochromatin variations fixed in homozygous condition as prominent short arms in autosomes 1, 3 and 6. The three chromosomal species exhibit a high incidence of polymorphisms for Robertsonian fusions and pericentric inversions. Breeding experiments and histological analysis of testis show that heterozygosity for pericentric inversions and Robertsonian fusions had no effect on fertility. Meiotic analysis shows normal overall progression of meiosis in the heterozygotes, which is consistent with their normal gametogenesis. Nevertheless, both the inversion and fusion heterozygotes had undergone some alterations in the regular process of homologous synapsis, and it appeared that certain features of the meiotic system circumvented the potential negative effects of these polymorphic chromosomal rearrangements. The results indicate that the attributes of the meiotic system in a given organism could modulate the potential of a chromosomal rearrangement as reproductive barrier. The meiotic modulation hypothesis offers an explanation for the contradictory effects of the similar kinds of chromosomal mutations reported in different species.     

Fitness differences associated with Pgi SNP genotypes in the Glanville fritillary butterfly (Melitaea cinxia)

Allozyme variation at the phosphoglucose isomerase (PGI) locus in the Glanville fritillary butterfly (Melitaea cinxia) is associated with variation in flight metabolic rate, dispersal rate, fecundity and local population growth rate. To map allozyme to DNA variation and to survey putative functional variation in genomic DNA, we cloned the coding sequence of Pgi and identified nonsynonymous variable sites that determine the most common allozyme alleles. We show that these single‐nucleotide polymorphisms (SNPs) exhibit significant excess of heterozygotes in field‐collected population samples as well as in laboratory crosses. This is in contrast to previous results for the same species in which other allozymes and SNPs were in Hardy–Weinberg equilibrium or exhibited an excess of homozygotes. Our results suggest that viability selection favours Pgi heterozygotes. Although this is consistent with direct overdominance at Pgi, we cannot exclude the possibility that heterozygote advantage is caused by the presence of one or more deleterious alleles at linked loci.     

Effects of centric fusions on chiasma frequency and position in Leptysma argentina (Acrididae: Orthoptera) I. Spontaneous and stable polymorphic centric fusions

Leptysma argentina is a highly polymorphic South-American grasshopper from the cytological point of view; all populations so far studied carry a polymorphic fusion between pairs 3 and 6. In heterozygotes, the trivalent 3-3/6-6 shows alternate orientation in 97.17% of the cells. Trivalent chiasma frequency is significantly lower than in the combined 3 and 6 bivalents of the standard homozygote; besides, there is a marked displacement of chiasmata to a distal position. In structural homozygotes the same effects, but not so marked, were observed.One individual was a double heterozygote for both the polymorphic centric fusion and a spontaneous one between pairs 5 and 7. The presence of a fragment, sometimes associated with the centromeric region of the nonfused 5 chromosome, was detected in more than 50% of the cells. The orientation of trivalent 5-5/7-7 in metaphase I was highly irregular (36% linear orientation). Neither frequency nor position of chiasmata were altered in trivalent 5-5/7-7 when compared with bivalents 5+7 of normal individuals.The results suggest that proximal and interstitial chiasma reduction observed in trivalent 3-3/6-6 of L. argentina is due to a later adaptation to the polymorphic condition or a fortuitous genetic condition present in the original mutant, rather than to a direct effect of the fusion itself on chiasma distribution.Fellow of the Consejo Nacional de Investigaciones Cientificas y Técnicas (CONICET)     

Genetic analysis of the yeastCandida maltosa by means of induced parasexual processes

The usefulness of hybridization by protoplast fusion and mitotic segregation for the genetic analysis of the imperfect fodder yeastCandida maltosa was tested. Mitotically stable fusion hybrids were obtained with frequencies between 10^–6 and 10^–7. Complementation tests were performed by protoplast fusion. Substances that are known to induce frequent mitotic segregation in other yeast species such as benomyl, p-fluorophenylalanine, and acriflavine were ineffective inC. maltosa. UV irradiation induced mitotic segregation in up to 10%. This agent induced mainly mitotic crossing over inC. maltosa. Our data enabled the construction of the linkage group I with the sequenceCEN-ade-26-pro-1.     

Origin,evolution, and population genetics of the selfish Segregation Distorter gene duplication in European and African populations of Drosophila melanogaster

Meiotic drive elements are a special class of evolutionarily “selfish genes” that subvert Mendelian segregation to gain preferential transmission at the expense of homologous loci. Many drive elements appear to be maintained in populations as stable polymorphisms, their equilibrium frequencies determined by the balance between drive (increasing frequency) and selection (decreasing frequency). Here we show that a classic, seemingly balanced, drive system is instead characterized by frequent evolutionary turnover giving rise to dynamic, rather than stable, equilibrium frequencies. The autosomal Segregation Distorter (SD) system of the fruit fly Drosophila melanogaster is a selfish coadapted meiotic drive gene complex in which the major driver corresponds to a partial duplication of the gene Ran‐GTPase activating protein (RanGAP). SD chromosomes segregate at similar, low frequencies of 1–5% in natural populations worldwide, consistent with a balanced polymorphism. Surprisingly, our population genetic analyses reveal evidence for parallel, independent selective sweeps of different SD chromosomes in populations on different continents. These findings suggest that, rather than persisting at a single stable equilibrium, SD chromosomes turn over frequently within populations.     

Enzyme and Chromosome Polymorphisms in Japanese Natural Populations of DROSOPHILA MELANOGASTER

Collections of D. melanogaster from Japanese populations were analyzed for enzyme and chromosomal polymorphisms. Allelic frequencies at the Adh and alphaGpd loci were compared with polymorphic inversion (In(2L)B, In(2R)C) frequencies in the second chromosome. There was a significant positive correlation between the frequencies of AdhS and In(2L)B, caused by linkage. On the other hand, inversion-free cage populations maintained in the laboratory for a long time showed considerably larger variation in the frequencies of these enzyme alleles, which seem very likely to be a consequence of random drift. Two fitness components of these enzyme and chromosomal variants were measured in two different environmental conditions; neither of the two loci showed heterozygote superiority in viability or productivity, while the inversion heterozygotes showed a superior productivity compared to the corresponding homozygotes in the fluctuating environment. These findings are compatible with the hypothesis that polymorphic isozyme genes are maintained by random drift of neutral genes in natural populations, and that association with linked inversions is a historical accident.     

Isolation of telotertiary compensating trisomics from telocentric translocation trisomics and telo-substituted translocation heterozygotes of rye (Secale cereale L.)

Telotertiary compensating trisomics (CTs) of rye (Secale cereale L.), in which the absence of one normal chromosome is compensated by the presence of a telocentric and a translocation chromosome, were isolated in progenies of telocentric translocation trisomics, and telo-substituted translocation heterozygotes, respectively. These two sources were obtained from crosses between five interchanges of the Wageningen translocation tester set, and telocentric normal trisomics (for IRS, IRL and 5RS), or telocentric substitutions (for IR and 3R), respectively. In test crosses with normal male plants, CTs were identified using either critical meiotic configurations, the segregation of karyotypes in selfed trisomic progenies, or the segregation of a marker located on the compensated chromosome. CT yields ranged from 0.0–6.3%. These frequencies were concluded to be determined mainly by the frequency of the exchanged segment of the translocation chromosome involved in the CT complex being associated at first meiotic metaphase (MI) in the source plants. The lower association frequencies result in the higher CT yields. The correlation between high association frequency of this segment and low CT yield suggests that infrequent adjacent orientation of one critical segment is also responsible for the origin of CTs. This agrees with cytogenetic theory.     

Inbreeding,heterozygote advantage and the evolution of neo-X and neo-Y sex chromosomes

Associations between heterozygosities at different loci are generated by inbreeding. This can cause a fusion or translocation involving a sex chromosome and an autosome to have a selective advantage, when there is selection in favour of heterozygotes. Population genetic models of Y-autosome and X-autosome rearrangments in populations mating by a mixture of full sib-matings and random mating are described, in which the rearrangements cause an autosomal locus with heterozygote advantage to become linked to the true sex chromosomes. Such rearrangements gain a selective advantage under a wide range of conditions. If they can invade, Y-autosome rearrangements always spread to fixation, whereas X-autosome rearrangements may be maintained as stable polymorphisms. The results are discussed in relation to data on breeding systems and karyotypic evolution in termites.     

tetra: an improved program for population genetic analysis of allotetraploid microsatellite data

Population genetic analysis of allotetraploid microsatellite data has lagged far behind that of diploid data, largely because of an inability to determine allele copy number for partial heterozygotes. tetrasat developed by Markwith et al. (2006) uses an iterative substitution process to account for all probable combinations of allele copy numbers in populations with partial heterozygote samples. However, tetrasat cannot deal with microsatellite data containing more than 15 partial heterozygotes, because of an exponential increase in genotype combinations. tetra can handle the microsatellite data containing infinite partial heterozygotes. In the program tetra, the frequencies of alleles are measured as the probability with which the known alleles occur in unknown allele locations. The Hardy–Weinberg expected heterozygosity and Nei's coefficient of gene differentiation are calculated based on allele frequencies. The mean and standard error of expected heterozygosity are estimated through bootstrap method.     

LOCAL ADAPTATION AND THE EVOLUTION OF CHROMOSOME FUSIONS

We use forward and coalescent models of population genetics to study chromosome fusions that reduce the recombination between two locally adapted loci. Under a continent–island model, a fusion spreads and reaches a polymorphic equilibrium when it causes recombination between locally adapted alleles to be less than their selective advantage. In contrast, fusions in a two‐deme model always spread; whether it reaches a polymorphic equilibrium or becomes fixed depends on the relative recombination rates of fused homozygotes and heterozygotes. Neutral divergence around fusion polymorphisms is markedly increased, showing peaks at the point of fusion and at the locally adapted loci. Local adaptation could explain the evolution of many of chromosome fusions, which are some of the most common chromosome rearrangements in nature.     

Association between MSX1 variants and oral clefts in Han Chinese in western China

Previous animal and association studies have shown that the MSX1 gene is associated with oral clefts. Our aim was to investigate association between variants in the MSX1 gene and oral clefts in a Han Chinese population. Our study group consisted of 206 nonsyndromic oral cleft (NSOC) nuclear families (including the patients and their parents) and 224 controls. The three variants evaluated in this study were single-nucleotide polymorphisms rs3821949 and rs12532 and a missense mutation P147Q. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the three markers. Case-control and family-based association analyses were carried out. In the case-control analysis, no significant differences in genotypic or allelic frequencies were observed in any of the two single-nucleotide polymorphisms between patients and controls. Although the homozygous T allele for P147Q was not detected in any sample in this population, heterozygotes were more prevalent in NSOC (1.2%) when compared with the controls (0%). The analyses for family-based association did not suggest association between any of the three variants and NSOC. No significant association was found between NSOC and rs3821949 or rs12532 in MSX1 gene, whereas an association was observed between the P147Q variant and cleft lip with cleft palate in the case-control analysis.     

Heterogeneity of chromosomal breakage levels in epithelial tissue of ataxia-telangiectasia homozygotes and heterozygotes

Summary The objective of this study was to obtain an estimate of the frequency distribution of spontaneous chromosomal breakage occurring in vivo in oral epithelia of 20 ataxiatelangiectasia patients (A-T homozygotes) and 26 parents (A-T obligate heterozygotes). Samples of exfoliated cells were obtained from each individual by swabbing the oral cavity and preparing air-dried slides. The percentage of exfoliated cells with micronuclei (MEC frequency) was used as an in vivo indicator for the amount of chromosomal breakage occurring in the tissue. As a population group, MEC frequencies of the A-T patients differed significantly from controls (mean for A-T patients, 1.51; for controls, 0.29; P<0.01). However, the values observed in individual patients ranged from MEC frequencies 10- to 12-fold above control values, to frequencies overlapping the upper values observed in the controls. Similarily, MEC frequencies observed among the A-T heterozygotes differed significantly from controls (mean for A-T heterozygotes, 1.02, mean for controls, 0.29; P<0.01). However, only 16 of the 26 individuals sampled had MEC frequencies >0.5%, the 90th percentile for controls (compared with 16 of the 20 A-T patients examined). Of the A-T patients 11 had been previously assigned to complementation groups on the basis of sensitivity to x-irradiation. Seven of the patients belonged to group A and had MEC frequencies ranging from 0.3% to 1.9% with the remaining patients belonging to group C with MEC frequencies of 0.2% to 0.9%. The data presented in this paper suggest that although levels of spontaneous breakage in epithelial tissues of A-T patients and A-T obligate heterozygotes are often significantly elevated, this is not the case in all individuals.     

Common polymorphisms in interleukin genes (IL4, IL6, IL8 and IL12) are not associated with alcoholic liver disease or alcoholism in Spanish men

Background: Preliminary data suggest that polymorphisms in cytokine genes may be involved in the genetic predisposition to alcoholic liver cirrhosis or alcohol use disorders. We thus analyze the association between these diseases and the following polymorphisms: −33T > C IL4, −174 G > C IL6, −251 T > A IL8 and 1188 A > C IL12B. Methods: 258 male alcoholics (161 without liver disease and 97 with liver cirrhosis) and 101 healthy controls were genotyped for the above mentioned polymorphisms. We examined the relationship between genotype and allele frequencies and the presence of disease, as well as the correlation with combinations of putative pro-inflammatory genotypes. Haplotypes were inferred using the expectation–maximization algorithm and haplotype frequencies were compared. Results: We found no statistically significant association between any of these polymorphisms or the combinations of pro-inflammatory polymorphisms and the risk of alcoholic liver cirrhosis or alcohol abuse or dependence. Haplotype analysis of the IL4 and IL12B polymorphisms did not show any statistical relationship either. Conclusions: Our results do not support the hypothesis that the analyzed polymorphisms confer differences in alcoholic liver cirrhosis or alcohol use disorders susceptibility.     

Experimental studies on some genetic effects of marine pollution

Following the results of a series of investigations carried out to estimate the degree of marine pollution by utilizing certain marine filter feeders, such as the blue musselMytilus galloprovincialis, research has been planned to detect possible genetic effects of pollutants, with special attention to those acting at the population level. The possible selective role of pollutants has been studied both in natural (Mytilus) and in experimental (Tisbe holothuriae) populations by utilizing some electrophoretically-detected gene-enzyme systems as genetic markers. For some of the seven polymorphic loci studied inMytilus (AP, LAP, 6-PGD, IDH_s, IDH_m, PGI, PGM) significant changes in gene frequencies have been detected which can be related to the degree of pollution in the sampling areas. In the more polluted areas these changes were accompanied by a decrease in the frequency of heterozygotes. Similar changes in gene frequencies also occurred in laboratory populations of the copepodTisbe, reared under various experimental conditions. In particular, certain alleles of two loci, PGI-1 and AP-1, exhibited an increase in frequency, especially in populations cultured at various levels of oil pollution. This trend appeared more significant for the locus PGI. The fact that equilibria are reached and that the less favoured alleles are nevertheless maintained in the populations, even at extremely low frequencies, suggests the balanced nature of these enzyme polymorphisms. The significance of the above findings is briefly discussed.     

Genetic variability in Muscari comosum L. (Liliaceae) IV Geographical distribution and adaptive role of the polymorphic variants of chromosome 2

Muscari comosum L. (Liliaceae) has a chromosomal polymorphism for a pericentric inversion and a supernumerary chromosome segment probably due to an unequal interchange or insertional translocation. Both arrangements are widely distributed throughout the species range and the mean genetic distance among populations is D=0.131±0.075. There are no correlations between genetic distance and geographic distance or latitude. Only appreciable decreases in the frequencies of the inversion are detected in populations with ecologically marginal characteristics. There is a permanent and extended association between chromosomal inversion and an enzymatic locus (ADH). An excess of individuals heterozygous for the inversion was found and female productivity of heterozygotes is higher than that of corresponding homozygotes. A low rate of inversion heterozygosity in populations with ecologically marginal characteristics could be explained by natural selection. With respect to the adaptive role of the segment, although no homozygotes are found and may be selected against, heterozygotes could have heterotic effects.