Reduced Polymorphism Associated with X Chromosome Meiotic Drive in the Stalk-Eyed Fly Teleopsis dalmanni

Sex chromosome meiotic drive has been suggested as a cause of several evolutionary genetic phenomena, including genomic conflicts that give rise to reproductive isolation between new species. In this paper we present a population genetic analysis of X chromosome drive in the stalk-eyed fly, Teleopsis dalmanni, to determine how this natural polymorphism influences genetic diversity. We analyzed patterns of DNA sequence variation at two X-linked regions (comprising 1325 bp) approximately 50 cM apart and one autosomal region (comprising 921 bp) for 50 males, half of which were collected in the field from one of two allopatric locations and the other half were derived from lab-reared individuals with known brood sex ratios. These two populations are recently diverged but exhibit partial postzygotic reproductive isolation, i.e. crosses produce sterile hybrid males and fertile females. We find no nucleotide or microsatellite variation on the drive X chromosome, whereas the same individuals show levels of variation at autosomal regions that are similar to field-collected flies. Furthermore, one field-caught individual collected 10 years previously had a nearly identical X haplotype to the drive X, and is over 2% divergent from other haplotypes sampled from the field. These results are consistent with a selective sweep that has removed genetic variation from much of the drive X chromosome. We discuss how this finding may relate to the rapid evolution of postzygotic reproductive isolation that has been documented for these flies

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The evolutionary genetics of recombination and segregation in Drosophila

Thesis (Ph. D.)--University of Rochester. Department of Biology, 2018.During meiosis, sexually reproducing eukaryotes exchange genetic material via recombination and segregate homologous chromosomes into gametes. Surprisingly, some genes involved in meiotic recombination and chromosomal segregation experience frequent evolutionary turnover. Growing evidence suggests selfish genetic elements— DNA entities that promote their own transmission at the expense of other genes in the genome— are a significant evolutionary force driving rapid molecular evolution at genes involved in an otherwise conserved biological process. The research in this dissertation integrates classical, molecular, and population genetics to study the evolution of recombination rates and biased chromosomal segregation in Drosophila. First, in Chapters 2-4, I focus on the evolution of recombination rates in Drosophila. In Chapter 2, I perform an evolutionary screen to identify a meiosis gene with a history of recurrent positive selection that might contribute to differences in the rate of crossing over between two closely related Drosophila species. I then use a transgenic approach to show this gene, mei-217/mei-218, mediates the species differences in the rate and patterning of crossing over. In Chapter 3, I use further transgenic analyses to functionally dissect mei-217/mei-218 to determine which gene regions control the species differences in crossing over. In Chapter 4, I explore the long-term molecular evolution of mei-217/mei-218 and find evidence for frequent positive selection during the phylogenetic history of Drosophila. I find that mei-217/mei-218 wildtype alleles of two additional Drosophila species have also functionally diverged in their control of crossing over. I speculate that recurrent bouts of adaptive functional evolution at mei-217/-218 might reflect a history of coevolution with selfish genetic elements. Next, in Chapter 5, I turn to the evolution of a meiotic drive system, Segregation Distorter, that causes biased segregation in Drosophila melanogaster. I use molecular and population genetic tools to investigate the age, geographic origins, and population dynamics of Segregation Distorter chromosomes. I find that despite its stable frequency, Segregation Distorter chromosomes experience frequent selective sweeps and replacement events

Positive Selection and Functional Divergence at Meiosis Genes That Mediate Crossing Over Across the Drosophila Phylogeny

Meiotic crossing over ensures proper segregation of homologous chromosomes and generates genotypic diversity. Despite these functions, little is known about the genetic factors and population genetic forces involved in the evolution of recombination rate differences among species. The dicistronic meiosis gene, mei-217/mei-218, mediates most of the species differences in crossover rate and patterning during female meiosis between the closely related fruitfly species, Drosophila melanogaster and D. mauritiana. The MEI-218 protein is one of several meiosis-specific mini-chromosome maintenance (mei-MCM) proteins that form a multi-protein complex essential to crossover formation, whereas the BLM helicase acts as an anti-crossover protein. Here we study the molecular evolution of five genes— mei-218, the other three known members of the mei-MCM complex, and Blm— over the phylogenies of three Drosophila species groups— melanogaster, obscura, and virilis. We then use transgenic assays in D. melanogaster to test if molecular evolution at mei-218 has functional consequences for crossing over using alleles from the distantly related species D. pseudoobscura and D. virilis. Our molecular evolutionary analyses reveal recurrent positive selection at two mei-MCM genes. Our transgenic assays show that sequence divergence among mei-218 alleles from D. melanogaster, D. pseudoobscura, and D. virilis has functional consequences for crossing over. In a D. melanogaster genetic background, the D. pseudoobscura mei-218 allele nearly rescues wildtype crossover rates but alters crossover patterning, whereas the D. virilis mei-218 allele conversely rescues wildtype crossover patterning but not crossover rates. These experiments demonstrate functional divergence at mei-218 and suggest that crossover rate and patterning are separable functions

Fasta File of Sd-RanGAP duplication

Alignment of Sd-RanGAP duplication from 52 SD chromosomes

Data from: 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 fruitfly 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

Data from: Rapid evolution of asymmetric reproductive incompatibilities in stalk-eyed flies

The steps by which isolated populations acquire reproductive incompatibilities remain poorly understood. One potentially important process is postcopulatory sexual selection because it can generate divergence between populations in traits that influence fertilization success after copulation. Here we present a comprehensive analysis of this form of reproductive isolation by conducting reciprocal crosses between variably diverged populations of stalk-eyed flies (Teleopsis dalmanni). First, we measure seven types of reproductive incompatibility between copulation and fertilization. We then compare fertilization success to hatching success to quantify hybrid inviability. Finally, we determine if sperm competition acts to reinforce or counteract any incompatibilities. We find evidence for multiple incompatibilities in most crosses, including failure to store sperm after mating, failure of sperm to reach the site of fertilization, failure of sperm to fertilize eggs, and failure of embryos to develop. Local sperm have precedence over foreign sperm, but this effect is due mainly to differences in sperm transfer and reduced hatching success. Crosses between recently diverged populations are asymmetrical with regard to the degree and type of incompatibility. Because sexual conflict in these flies is low, postcopulatory sexual selection, rather than antagonistic coevolution, likely causes incompatibilities due to mismatches between male and female reproductive traits

Measures of competitive gametic isolation

Second male sperm precedence scored from microsatellite genotypes of 10-20 progeny produced by females of a population mated to two males from the same or different population. Populations used are Gombak, Soraya, and Lawang

Data from: Haldane's rule is linked to extraordinary sex ratios and sperm length in stalk-eyed flies.

We use three allopatric populations of the stalk-eyed fly Teleopsis dalmanni from Southeast Asia to test two predictions made by the sex chromosome drive hypothesis for Haldane's rule. The first is that modifiers that suppress or enhance drive should evolve rapidly and independently in isolated populations. The second is that drive loci or modifiers should also cause sterility in hybrid males. We tested these predictions by assaying the fertility of 2,066 males derived from backcross experiments involving two pairs of populations and found that the proportion of mated males that fail to produce any offspring ranged from 38-60% among crosses with some males producing strongly female-biased or male-biased sex ratios. After genotyping each male at 25-28 genetic markers we found quantitative trait loci (QTL) that jointly influence male sterility, sperm length and biased progeny sex ratios in each pair of populations, but almost no shared QTL between population crosses. We also discovered that the extant XSR chromosome has no effect on sex ratio or sterility in these backcross males. Whether shared QTL are caused by linkage or pleiotropy requires additional study. Nevertheless, these results indicate the presence of a "cryptic" drive system that is currently masked by suppressing elements that are associated with sterility and sperm length within but not between populations and, therefore, must have evolved since the populations became isolated, i.e. in less than 100,000 years. We discuss how genes that influence sperm length may contribute to hybrid sterility

Nucleotide diversity for (A) the two X-linked regions and (B) the two autosomal regions.

<p>Sections containing variable repeats have been removed and estimates are from a sliding window with length 100 and step size 5 bp. An intron in <i>crc</i> occurs between 200 and 260 bp in the alignment. <i>Cryptocephal</i> and ms125 are separated by 50 cM on <i>X^ST</i> chromosomes. The bnbUTR is approximately 620 bp 3′ from the sequenced portion of the coding region. Field collected samples are labeled Gf for Gombak and Sf for Soraya. Lab population samples are labeled Gst for Gombak males carrying <i>X^ST</i> and Gd for Gombak males carrying <i>X^D</i> as explained in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0027254#pone-0027254-g001" target="_blank">Fig. 1</a>.</p