Imbalanced segregation of recombinant haplotypes in hybrid populations reveals inter- and intrachromosomal Dobzhansky-Muller incompatibilities.

Dobzhansky-Muller incompatibilities (DMIs) are a major component of reproductive isolation between species. DMIs imply negative epistasis and are exposed when two diverged populations hybridize. Mapping the locations of DMIs has largely relied on classical genetic mapping. Approaches to date are hampered by low power and the challenge of identifying DMI loci on the same chromosome, because strong initial linkage of parental haplotypes weakens statistical tests. Here, we propose new statistics to infer negative epistasis from haplotype frequencies in hybrid populations. When two divergent populations hybridize, the variance in heterozygosity at two loci decreases faster with time at DMI loci than at random pairs of loci. When two populations hybridize at near-even admixture proportions, the deviation of the observed variance from its expectation becomes negative for the DMI pair. This negative deviation enables us to detect intermediate to strong negative epistasis both within and between chromosomes. In practice, the detection window in hybrid populations depends on the demographic scenario, the recombination rate, and the strength of epistasis. When the initial proportion of the two parental populations is uneven, only strong DMIs can be detected with our method unless migration prevents parental haplotypes from being lost. We use the new statistics to infer candidate DMIs from three hybrid populations of swordtail fish. We identify numerous new DMI candidates, some of which are inferred to interact with several loci within and between chromosomes. Moreover, we discuss our results in the context of an expected enrichment in intrachromosomal over interchromosomal DMIs

Genetics of Intraspecies Variation in Avoidance Behavior Induced by a Thermal Stimulus in Caenorhabditis elegans.

Individuals within a species vary in their responses to a wide range of stimuli, partly as a result of differences in their genetic makeup. Relatively little is known about the genetic and neuronal mechanisms contributing to diversity of behavior in natural populations. By studying intraspecies variation in innate avoidance behavior to thermal stimuli in the nematode Caenorhabditis elegans, we uncovered genetic principles of how different components of a behavioral response can be altered in nature to generate behavioral diversity. Using a thermal pulse assay, we uncovered heritable variation in responses to a transient temperature increase. Quantitative trait locus mapping revealed that separate components of this response were controlled by distinct genomic loci. The loci we identified contributed to variation in components of thermal pulse avoidance behavior in an additive fashion. Our results show that the escape behavior induced by thermal stimuli is composed of simpler behavioral components that are influenced by at least six distinct genetic loci. The loci that decouple components of the escape behavior reveal a genetic system that allows independent modification of behavioral parameters. Our work sets the foundation for future studies of evolution of innate behaviors at the molecular and neuronal level

High-resolution mapping reveals hundreds of genetic incompatibilities in hybridizing fish species

Hybridization is increasingly being recognized as a common process in both animal and plant species. Negative epistatic interactions between genes from different parental genomes decrease the fitness of hybrids and can limit gene flow between species. However, little is known about the number and genome-wide distribution of genetic incompatibilities separating species. To detect interacting genes, we perform a high-resolution genome scan for linkage disequilibrium between unlinked genomic regions in naturally occurring hybrid populations of swordtail fish. We estimate that hundreds of pairs of genomic regions contribute to reproductive isolation between these species, despite them being recently diverged. Many of these incompatibilities are likely the result of natural or sexual selection on hybrids, since intrinsic isolation is known to be weak. Patterns of genomic divergence at these regions imply that genetic incompatibilities play a significant role in limiting gene flow even in young species

Analysis of ancestry heterozygosity suggests that hybrid incompatibilities in threespine stickleback are environment dependent

Hybrid incompatibilities occur when interactions between opposite ancestry alleles at different loci reduce the fitness of hybrids. Most work on incompatibilities has focused on those that are “intrinsic,” meaning they affect viability and sterility in the laboratory. Theory predicts that ecological selection can also underlie hybrid incompatibilities, but tests of this hypothesis using sequence data are scarce. In this article, we compiled genetic data for F(2) hybrid crosses between divergent populations of threespine stickleback fish (Gasterosteus aculeatus L.) that were born and raised in either the field (seminatural experimental ponds) or the laboratory (aquaria). Because selection against incompatibilities results in elevated ancestry heterozygosity, we tested the prediction that ancestry heterozygosity will be higher in pond-raised fish compared to those raised in aquaria. We found that ancestry heterozygosity was elevated by approximately 3% in crosses raised in ponds compared to those raised in aquaria. Additional analyses support a phenotypic basis for incompatibility and suggest that environment-specific single-locus heterozygote advantage is not the cause of selection on ancestry heterozygosity. Our study provides evidence that, in stickleback, a coarse—albeit indirect—signal of environment-dependent hybrid incompatibility is reliably detectable and suggests that extrinsic incompatibilities can evolve before intrinsic incompatibilities

HYBRIDIZATION AND SPECIATION IN SWORDTAIL FISH (POECILIIDAE: XIPHOPHORUS)

Understanding what makes a species is fundamental to understanding evolutionary biology, yet there is so much about this process that still puzzles us. Until recently, mating between different species, or hybridization, was thought to be a rare event. With the advent of genome sequencing, biologists began to realize that hybridization is remarkably common throughout the tree of life. Despite this realization that hybridization is common, there is much we do not know about its evolutionary effects. In my dissertation work, I use a combination of genomic and computational techniques to ask how selection on hybrids shapes the genomes and evolution of hybrids and parental species. As a model system for this work, I focus on a group of freshwater fish, the swordtails (Poeciliidae: Xiphophorus). In my first chapter, I examine the genome of a proposed hybrid species, the swordtail fish Xiphophorus clemenciae. In my second chapter, I return to the question of hybrid speciation using theoretical and simulation approaches. I use models that describe how gene combinations that are under selection in hybrids (or “hybrid incompatibilities”) to predict how these regions of the genome will evolve in hybrids, and potentially contribute to reproductive isolation between hybrids and parent species. In my third chapter, I study the genomes of recent, natural hybrids between the sister species X. birchmanni and X. malinche. I identify on the order of two hundred pairs of hybrid incompatibilities and find evidence that these loci may actually play a role in limiting gene flow between species at functionally important genomic regions. In my fourth chapter, I study an ancient hybridization event between the swordtail fish X. nezahualcoyotl and X. cortezi. I find that at least two thousand generations have passed since initial hybridization in these species, allow time for selection to act on hybrid ancestry in the genome. I find that selection has constrained what regions of the genome are hybridization-derived to less functionally essential genomic regions. Overall, my dissertation work yields new insights into the importance of hybridization in speciation and how selection acts on hybridization-derived regions to shape hybrid ancestry in the genome

create_insnp_oneindiv_GATK3_4_v7

script to generate insnp file from GATK gVCF files. Must be run on each chromosome separately

Xiphophorus_maculatus_LG.Xipmac4.4.2.81

modified gtf file for the X. maculatus genome used in analysi

compressed neutral simulation files for reproduction of results figure 2

"neutral.zip" contains neutral simulation results files and scripts needed to reproduce figure 2 in the main tex

configuration files and admix'em input file for neutral simulations

Required files to run neutral simulations including three admix'em configuration files for neutral hybrid swarm (admixsimul.cfg), neutral bottleneck hybrid swarm (admixsimul_bottle.cfg), and neutral hybrid swarm with migration simulations (admixsimul_mig.cfg) and other input files to admix'em called by these configuration file

Data from: Determining epistatic selection in admixed populations

When two diverging species begin hybridizing, selection against hybridization is likely driven not by single substitutions, but by interactions between incompatible mutations. To identify these incompatibilities in natural populations, researchers examine the extent of non-random associations between ancestry at physically unlinked loci in admixed populations. In this approach, which we call “AD scans”, locus-pairs with significantly positive “ancestry disequilibrium” (AD, i.e. locus-pairs that positively covary by ancestry) represent incompatible alleles. Past research has uniformly revealed an excess of locus-pairs with significantly positive AD, suggesting that dozens to hundreds of incompatibilities separate species. With forward simulations, we show that many realistic demographic scenarios, including recent and/or ongoing contact, generate a bias towards positive ancestry disequilibrium. We suggest steps that researchers can take to avoid pitfalls in interpreting AD scans, and present a novel measure of AD, which minimizes but does not fully eliminate bias in the AD distribution. We also show, by simulation, that the tail of the AD distribution is enriched for true incompatibilities. To illustrate the potential power and appropriate caution in interpretation of AD scans, we reanalyze previously published data from two admixed populations of Xiphophorus fishes. Our results imply that the prevalence of positive LD in admixed populations does not in itself support the idea that two-locus incompatibilities are widespread, but the co-enrichment of top AD hits across the two Xiphophorus populations supports the idea that AD scans can identify candidate interspecific incompatibilities