Unravelling the mystery of female meiotic drive: where we are

Female meiotic drive is the phenomenon where a selfish genetic element alters chromosome segregation during female meiosis to segregate to the egg and transmit to the next generation more frequently than Mendelian expectation. While several examples of female meiotic drive have been known for many decades, a molecular understanding of the underlying mechanisms has been elusive. Recent advances in this area in several model species prompts a comparative re-examination of these drive systems. In this review, we compare female meiotic drive of several animal and plant species, highlighting pertinent similarities.

Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus, chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, and are not mediated by random maternal effects. SRD exhibits a heritable component, but QTL mapping analyses fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We explore several potential complex genetic mechanisms for SRD, including allelic interactions leading to sex-biased lethality, genetic sex reversal, chromosome drive mediated by sex-linked selfish elements, and incompatibilities between specific maternal and paternal genotypes. We show that no one mechanism offers a singular explanation for this population-wide SRD. Instead, our data present preliminary evidence for the action of distinct mechanisms of SRD at play in different strains. Taken together, our work exposes the pervasiveness of SRD in the CC population and nominates the CC as a powerful resource for investigating diverse genetic causes of biased sex chromosome transmission.

Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative Cross Mouse Mapping Population

In species with single-locus chromosome-based mechanisms of sex determination, the laws of segregation predict an equal ratio of females to males at birth. Here, we show that departures from this Mendelian expectation are commonplace in the 8-way recombinant inbred Collaborative Cross (CC) mouse population. More than one-third of CC strains exhibit significant sex ratio distortion (SRD) at wean, with twice as many male-biased than female-biased strains. We show that these pervasive sex biases persist across multiple breeding environments, are stable over time, are not fully mediated by maternal effects, and are not explained by sex-biased neonatal mortality. SRD exhibits a heritable component, but QTL mapping analyses and targeted investigations of sex determination genes fail to nominate any large effect loci. These findings, combined with the reported absence of sex ratio biases in the CC founder strains, suggest that SRD manifests from multilocus combinations of alleles only uncovered in recombined CC genomes. We speculate that the genetic shuffling of eight diverse parental genomes during the early CC breeding generations led to the decoupling of sex-linked drivers from their co-evolved suppressors, unleashing complex, multiallelic systems of sex chromosome drive. Consistent with this interpretation, we show that several CC strains exhibit copy number imbalances at co-evolved X- and Y-linked ampliconic genes that have been previously implicated in germline genetic conflict and SRD in house mice. Overall, our findings reveal the pervasiveness of SRD in the CC population and nominate the CC as a powerful resource for investigating sex chromosome genetic conflict in action.

Early Effect of Inbreeding as Revealed by Microsatellite Analyses on Ostrea edulis Larvae

This paper reports new experimental evidence on the effect of inbreeding on growth and survival in the early developmental phase of a marine bivalve, the flat oyster Ostrea edulis. Two crosses between full sibs were analyzed using four microsatellite markers. Samples of 96 individuals were taken just after spawning (day 1), at the end of the larval stage before metamorphosis (day 10) and at the postlarval stage (day 70). Significant departure from Mendelian expectation was observed at two loci in the first cross and two loci in the second. Departure from 1:1 segregation occured in one parent of the first cross at three loci and genotypic selection, which resulted in highly significant heterozygote excesses, was recorded at three out of four loci in cross C1 and at two out of three loci in cross C2. Across the four markers, there were similar significant excesses of multilocus heterozygosity, and significant multilocus heterozygosity–growth correlations were recorded for both crosses at all stages. These results suggest that microsatellite markers, often assumed to be neutral, cosegregated with fitness-associated genes, the number of which is estimated to be between 15 and 38 in the whole genome, and that there is a potentially high genetic load in Ostrea edulis genome. This load provides a genetic basis for heterosis in marine bivalves.

An empirical test of the meiotic drive models of hybrid sterility: sex-ratio data from hybrids between Drosophila simulans and Drosophila sechellia.

Recently, there has been much discussion regarding the hypothesis that divergence of meiotic drive systems in isolated populations can generate the patterns of reproductive isolation observed in animal hybridizations. One prediction from this hypothesis is that the sex ratio of hybrids with heterospecific sex chromosomes should greatly deviate from the Mendelian expectation of 50% female. From sex-ratio data in our Drosophila hybridization studies, we find no such deviation: the sex ratio of offspring of males with introgressed heterospecific Y chromosomes with various autosomal backgrounds does not differ from that of the pure species. We also discuss other aspects of the current meiotic drive models.

Do histocompatibility genes influence sex ratio (% males)?

Breeding records for 15 of the 42 C57BL/10SnJ Congenic Histocompatibility Mouse Strains from the Special Mouse Stocks Resource (SMSR) showed three with a significant excess of male offspring. Strain B10.R111(71NS), hereafter R, gave the highest proportion of males (55.68 +/- 0.59% of 7129 newborn) which is significantly more than the proportion of male offspring (49.81 +/- 0.94% of 2853 newborn) from the C57BL/10SnJ progenitor strain, hereafter B. All mice in the SMSR colonies were fed Old Guildford 96 and Old Guildford 96W liberally on alternate weeks. Breeding females of B and R strains were established in a research colony at the Jackson Laboratory under conditions similar to those in SMSR except that they were fed Wayne Sterilizable Rodent Blox. More than 5000 inbred, hybrid and backcross fetuses were examined but no evidence of an excess of males was found. Also, there were no strain differences in the neonatal data. However, the sex ratio of the 4396 neonates was just significantly higher (P less than 0.05) than that of the fetuses, indicating some perinatal loss of females. An even greater loss of females was most probably the cause of the high sex ratios in the preliminary and follow-up surveys of SMSR R mice, which we ascribe to an interaction between the H-2 haplotype of the R strain, or a gene linked thereto, and the Old Guildford diet that is unfavourable to female survival. The sex ratio of fetuses agreed so closely with the Mendelian expectation as to indicate that the primary sex ratio was 50% males and that the R strain is not a model for the human male bias. There were no hermaphrodites or twins and the sex ratio of the fetuses in litters without resorptions was normal. These findings emphasize the variability of presumptive secondary sex ratios.

INTERACTION IN TRANSMISSION FREQUENCY BETWEEN THE SECOND AND THE THIRD CHROMOSOMES IN DROSOPHILA MELANOGASTER

ABSTRACT Wild second and third chromosomes from isofemale lines established from wild-inseminated females captured in natural populations of Drosophila melanogaster in Hawaii, New York, North Carolina and Texas were made heterozygous in males with marked second and third chromosomes from a laboratory strain, and the transmission frequencies of the wild second (= k 2) and the third (= k 3) chromosomes from the heterozygous male parents were measured. Based upon the preliminary tests of k 2, the isofemale lines were classified into two groups; group A included those lines showing average k 2 values considerably smaller than the Mendelian expectation of 0.5, and group B included those lines showing average k 2 values close to 0.5. Effects of the wild second chromosomes on k 2 in group A were suppressed (the average k 2 values increased) by the presence of the wild third chromosomes, whereas the wild second chromosomes in this group, in turn, caused a decrease in k 3 of the wild third chromosomes. The intensities of the observed effects were more or less comparable in their absolute values, and these phenomena do not appear to be due to differential viabilities of zygotes. No such interaction was observed between the wild second and third chromosomes in group B. An extention of the model of the Segregation Distorter system of D. melanogaster, as well as a model based upon the P-M system of hybrid dysgenesis, may explain the observed results.

Carrier Detection In Hemophilia I“A” Using Discriminant Analysis: A 5 Year Study

We counseled 174 possible or obligatory carriers of hemophilia “A” between January 1975-January 1980. Pedigree information provided a pedigree probability, πC, and blood samples the likelihood ratio favoring carriership (L.R.). The latter was arrived at from 2 bioassays of F. VIII activity (VIII:C & VIIIR:Ag) by linear discriminant analysis. Each consultand received counsel based on a final probability, P(C), produced by combining πC and L.R. Eighty % of the values of P(C) were either very high or very low which meant that clear-cut advice could usually be given. There were 29 obligatory carriers, 16 mothers of sporadic hemophiliacs, 73 sisters of hemophiliacs, and 56 more distant relatives. The individual values of P(C) could be used within each subset of carriers to relate mendelian expectation and observation. There were very few low P(C)s among mothers of sporadics suggesting that almost all were carriers. As a result, we now consider 0.8 to be a conservative πc for mothers of sporadics. Four women with low P(C)s were present among 29 obligatory carriers. This provided an estimate of negative diagnostic error (4/29=14%) and probably represented the effects of “lyonization”. The observedrexpected ratios of high:low P(C)s were normal among sisters of hemophiliacs and second and third degree relatives. Ten % of our consultands were pregnant when first seen. Twelve mothers with low P(C)s produced 11 liveborn, non-hemophilic children, 7 girls and 4 boys. Four with high P(C)s requested amniocentesis; 3 males were discovered and 2 were aborted. Five possible carriers with high P(C)s who had been seen before pregnancy, returned for assistance after becoming pregnant. All 5 requested amniocentesis, and fetoscopy if a male were present, and 4 males were fetoscoped. Two diagnosed as non-hemophilic in utero proved to be normal after delivery. A third could not be diagnosed, but was non-hemophilic at birth. The fourth, a hemophiliac, did not survive the procedure.

ESTIMATION OF FITNESS COMPONENTS IN DROSOPHILA MELANOGASTER. II. INFLUENCE OF REDUCED TRANSMISSION FREQUENCY

ABSTRACT Results are presented of further analyses of the significant effects of reciprocal crosses reported by KATZ and CARDELLINO(1978) in regard to viability indices of wild-type second chromosome heterozygotes. The observed differences between reciprocal crosses can be explained by the existence of reduced transmission frequencies of the wild-type homologue from Pm/+ and Cy/+ paternal parents. Mean estimates of transmission frequencies from Pm/+ and cy/+ males in California and Japan populations are significantly less than the Mendelian expectation of 1/2. The transmission frequencies of +i chromosomes from Pm/+i and Cy/+i males are also found to be positively correlated in the California and pooled populations, suggesting that the degree of distortion is primarily due to the +i chromosome rather than to Cy or Pm. A sufficient estimator of relative viability that is independent of distorted transmission frequencies is derived for use in the Cy/Pm technique of viability estimation.

FURTHER EVIDENCE FOR SELECTIVE DIFFERENCES BETWEEN ISOALLELES IN DROSOPHILA

ABSTRACT A number of separate strains of Drosophila pseudoobscura were inbred for 38 generations of brother-sister mating with forced heterozygosity for two alleles of either the octanol dehydrogenase or esterase-5 locus. Crosses were set up within each of these inbred lines such that simple mendelian ratios were expected, and eggs from these crosses were placed on media with additions of simple chemicals likely to interact with alleles of the two loci—octanol and ethanol for the ODH locus and tributyrin and triacetin for the E-5 locus. Similar crosses were set up involving parental flies with normally heterozygous genetic background as a control.—Significant deviations from mendelian expectation were observed in inbred E-5 flies grown on tributyrin, inbred ODH males grown on octanol, and inbred ODH females grown on ethanol. There was also a strong effect of octanol medium on males of one of the inbred E-5 lines, and a weak effect of tributyrin medium on ODH inbred females.—The probability that these results reflect interactions between these loci and the environment is assessed in the light of differences between the present results and those obtained at earlier stages of inbreeding.