Biology subjects

Koury, S. A.

Publications and source records attributed to Koury, S. A..

5 recordsLinked to original sources

bioRxiv2026

An extension of the Cx(Co)m model of crossover patterning to account for experimental mortality in Drosophila melanogaster

Classic recombination experiments designed to test genetic and environmental treatments do not directly measure crossing-over, instead rates and distribution of meiotic events in F1 meiocytes is inferred from genetic markers in F2 adults. In Drosophila melanogaster females this procedure introduces a substantial "missing data problem" because 75% of meiotic chromatids segregate to polar body nuclei and another 11% are transmitted to inviable F2 zygotes which cannot be scored for recombination. To address these sources of uncertainty and bias we extend the Cx(Co)m model of the data-generating process by assuming: 1) programmed double strand breaks occur as a Poisson point process, 2) crossover maturation is a stationary renewal process, 3) chromosome segregation is random one-half thinning of this process, 4) fertilization by X-versus Y-bearing sperm is mendelian, and 5) egg-to-adult survival is binomially distributed with a rate parameter determined by F2 marker alleles. To quantify experimental mortality, we performed egg counts in a 6-point X chromosome testcross and marker-free controls on identical genetic backgrounds under standard laboratory conditions. The 19,927 fly dataset reveals 44% F2 experimental mortality, and likelihood ratio tests support a model where 36 of the 44% is due to sex-specific, marker-associated viability defects. Variability in X chromosome genetic lengths with experimental mortality can be simulated and we provide case-control 80% power curves to guide experimental design. We propose that differential mortality should be the de facto null hypothesis when comparing F2 recombinant fractions and provide probabilistic models of the data-generating process to improve characterization of patterns in F1 meiotic events.

genetics↗

bioRxiv2018

Extensive recombination suppression and chromosome-wide differentiation of a segregation distorter in Drosophila

Segregation distorters violate Mendelian Inheritance by over-representing themselves in the progeny of carrier individuals and are commonly associated with chromosomal inversions. When distorting alleles are found on sex chromosomes, the progeny of carrier individuals will exhibit skewed sex ratios, as exemplified by the array of Sex-Ratio (SR) distorting chromosomes found in Drosophila. Because of the strong selective pressures such chromosomes are thought to inflict on genomes, segregation distorters and their associated inversions are expected to experience rapid turn-over. However, the SR X-chromosome of Drosophila pseudoobscura is found at high frequencies in natural populations, forms stable latitudinal clines, appears to be unsuppressed, and shows evidence of being quite long-lived. Despite being a historically significant and well-studied segregation distortion system, the mechanisms allowing for the long-term persistence of the D. pseudoobscura SR chromosome remain unclear. Here, we perform a comparative genomic analysis between SR and uninverted standard X-chromosomes in D. pseudoobscura to study its evolutionary history and dynamics. We find a substantial level of differentiation between the SR and standard chromosome and estimate that the associated inversions have likely existed for the entire lifetime of the species (> 2 million generations). Through direct recombination experiments and population genetic analyses, we infer that this high level of differentiation is maintained by a combination of suppressed recombination and epistatic selection. Finally, our data reveal a massive mutational target size for protein and expression level changes specific to SR generated by its three non-overlapping inversions. Together our results imply that the entire SR chromosome in D. pseudoobscura behaves as a single co-adapted gene complex and has been maintained through a combination of suppressed recombination and epistatic selection. This finding highlights the dramatic consequences segregation distorters can have in shaping chromosome-wide patterns of recombination, nucleotide variation, and gene expression.

evolutionary biology↗

bioRxiv2018

Meiotic Drive and the Survival Probability of Newly Inverted Chromosomes

When a new gene arrangement is generated by spontaneous mutation its survival is uncertain and largely unaffected by associated fitness effects. However, if a new chromosomal inversion is introduced into a population already polymorphic for inversions, then its survival probability will be a function of the relative size, position, and linkage phase of the gene rearrangements. This dependence on structural features is due to the complex meiotic behavior of overlapping inversions generating asymmetric dyads, which in turn cause both underdominance and meiotic drive/drag. Therefore, survival probabilities of new inversions can be expressed in terms of the probability of forming an asymmetric dyad via crossing over in meiosis I and the probability of recovery from that asymmetric dyad during disjunction in meiosis II. This model of female meiotic drive was parameterized with data from published experiments on laboratory constructs in Drosophila melanogaster. Generalizing this analysis to all possible inversions predicts a bias towards larger, proximally located inversions having a shorter persistence time in populations. These population genetic predictions are consistent with cytological evidence from natural populations of D. melanogaster. This research mathematically formalizes a cytogenetic mechanism for female meiotic drive/drag as the major force governing behavior of new gene arrangements entering populations, and therefore determining the genomic distribution of segregating inversion polymorphism.

evolutionary biology↗

bioRxiv2018

Novitski’s Distal shift in Paracentric Inversion Evolution

In Drosophila pseudoobscura younger chromosomal inversions tend to be found distal to older inversions. By examining phylogenetic series of overlapping inversions for 134 gene arrangements of 13 chromosomes this pattern was extended to five additional Drosophila species. This distinct pattern arose repeatedly and independently in all six species and likely reflects an underlying principle of chromosome evolution. In this study it is illustrated how transmission of distal inversions is always favored in female meiosis when crossing over in homosequential regions of overlapping inversions generates asymmetric dyads. This cytogenetic mechanism for female meiotic drive is described in detail and advanced as an explanation for the distal shift in phylogenetic series of overlapping inversions as well as several better known patterns in the evolution of serially inverted chromosomes.

evolutionary biology↗

bioRxiv2018

Interference hypothesis for recombination suppression in chromosomal inversion heterozygotes: A formal genetics analysis in Drosophila melanogaster

Suppressed recombination in chromosomal inversion heterozygotes is a well-known but poorly understood phenomenon. Recombination suppression is the result of at least four different regional effects of inversion heterozygosity; surprisingly, this includes areas outside inversions where there are no barriers to normal pairing, synapsis, double strand break formation, or recovery of crossover products. The interference hypothesis of recombination suppression proposes heterozygous inversion breakpoints possess chiasma-like properties such that recombination suppression extends from breakpoints in a process analogous to crossover interference. This hypothesis is qualitatively consistent with chromosome-wide patterns of recombination suppression, unifying the various regional effects under a single mechanism. The present study generates quantitative predictions for this hypothesis using a probabilistic model of crossover interference as a stationary renewal point process with gamma-distributed interarrival distances. These predictions were tested with formal genetic data (>40,000 meioses) on crossing-over in intervals external and adjacent to four cosmopolitan inversions of Drosophila melanogaster. The decay of recombination suppression differs for each of the four cosmopolitan inversions, with a strong dependence on proximity to the centromere. Counterintuitively, greater than expected recombination was observed in centromeric regions for the most proximally placed inversions. Structural features of chromosomes are discussed as potentially confounding variables in modelling recombination suppression. The true form of the decay function is not currently known and will require high-resolution mapping of rare crossover events in regions immediately adjacent to inversion breakpoints. A simple extension of the present experimental system can be conducted as a genetic screen for those rare crossover events.

genetics↗