John E. Pool

Genomic Variation in Natural Populations of Drosophila melanogaster

This report of independent genome sequences of two natural populations of Drosophila melanogaster (37 from North America and 6 from Africa) provides unique insight into forces shaping genomic polymorphism and divergence. Evidence of interactions between natural selection and genetic linkage is abundant not only in centromere- and telomere-proximal regions, but also throughout the euchromatic arms. Linkage disequilibrium, which decays within 1 kbp, exhibits a strong bias toward coupling of the more frequent alleles and provides a high-resolution map of recombination rate. The juxtaposition of population genetics statistics in small genomic windows with gene structures and chromatin states yields a rich, high-resolution annotation, including the following: (1) 5′- and 3′-UTRs are enriched for regions of reduced polymorphism relative to lineage-specific divergence; (2) exons overlap with windows of excess relative polymorphism; (3) epigenetic marks associated with active transcription initiation sites overlap with regions of reduced relative polymorphism and relatively reduced estimates of the rate of recombination; (4) the rate of adaptive nonsynonymous fixation increases with the rate of crossing over per base pair; and (5) both duplications and deletions are enriched near origins of replication and their density correlates negatively with the rate of crossing over. Available demographic models of X and autosome descent cannot account for the increased divergence on the X and loss of diversity associated with the out-of-Africa migration. Comparison of the variation among these genomes to variation among genomes from D. simulans suggests that many targets of directional selection are shared between these species.

Population Genomics of Sub-Saharan Drosophila melanogaster: African Diversity and Non-African Admixture

Drosophila melanogaster has played a pivotal role in the development of modern population genetics. However, many basic questions regarding the demographic and adaptive history of this species remain unresolved. We report the genome sequencing of 139 wild-derived strains of D. melanogaster, representing 22 population samples from the sub-Saharan ancestral range of this species, along with one European population. Most genomes were sequenced above 25X depth from haploid embryos. Results indicated a pervasive influence of non-African admixture in many African populations, motivating the development and application of a novel admixture detection method. Admixture proportions varied among populations, with greater admixture in urban locations. Admixture levels also varied across the genome, with localized peaks and valleys suggestive of a non-neutral introgression process. Genomes from the same location differed starkly in ancestry, suggesting that isolation mechanisms may exist within African populations. After removing putatively admixed genomic segments, the greatest genetic diversity was observed in southern Africa (e.g. Zambia), while diversity in other populations was largely consistent with a geographic expansion from this potentially ancestral region. The European population showed different levels of diversity reduction on each chromosome arm, and some African populations displayed chromosome arm-specific diversity reductions. Inversions in the European sample were associated with strong elevations in diversity across chromosome arms. Genomic scans were conducted to identify loci that may represent targets of positive selection within an African population, between African populations, and between European and African populations. A disproportionate number of candidate selective sweep regions were located near genes with varied roles in gene regulation. Outliers for Europe-Africa FST were found to be enriched in genomic regions of locally elevated cosmopolitan admixture, possibly reflecting a role for some of these loci in driving the introgression of non-African alleles into African populations.

The Drosophila Genome Nexus: A Population Genomic Resource of 623 Drosophila melanogaster Genomes, Including 197 from a Single Ancestral Range Population

Hundreds of wild-derived Drosophila melanogaster genomes have been published, but rigorous comparisons across data sets are precluded by differences in alignment methodology. The most common approach to reference-based genome assembly is a single round of alignment followed by quality filtering and variant detection. We evaluated variations and extensions of this approach and settled on an assembly strategy that utilizes two alignment programs and incorporates both substitutions and short indels to construct an updated reference for a second round of mapping prior to final variant detection. Utilizing this approach, we reassembled published D. melanogaster population genomic data sets and added unpublished genomes from several sub-Saharan populations. Most notably, we present aligned data from phase 3 of the Drosophila Population Genomics Project (DPGP3), which provides 197 genomes from a single ancestral range population of D. melanogaster (from Zambia). The large sample size, high genetic diversity, and potentially simpler demographic history of the DPGP3 sample will make this a highly valuable resource for fundamental population genetic research. The complete set of assemblies described here, termed the Drosophila Genome Nexus, presently comprises 623 consistently aligned genomes and is publicly available in multiple formats with supporting documentation and bioinformatic tools. This resource will greatly facilitate population genomic analysis in this model species by reducing the methodological differences between data sets.

Measures of linkage disequilibrium among neighbouring SNPs indicate asymmetries across the house mouse hybrid zone

Theory predicts that naturally occurring hybrid zones between genetically distinct taxa can move over space and time as a result of selection and/or demographic processes, with certain types of hybrid zones being more or less likely to move. Determining whether a hybrid zone is stationary or moving has important implications for understanding evolutionary processes affecting interactions in hybrid populations. However, direct observations of hybrid zone movement are difficult to make unless the zone is moving rapidly. Here, evidence for movement in the house mouse Mus musculus domesticus × Mus musculus musculus hybrid zone is provided using measures of LD and haplotype structure among neighbouring SNP markers from across the genome. Local populations of mice across two transects in Germany and the Czech Republic were sampled, and a total of 1301 mice were genotyped at 1401 markers from the nuclear genome. Empirical measures of LD provide evidence for extinction and (re)colonization in single populations and, together with simulations, suggest hybrid zone movement because of either geography‐dependent asymmetrical dispersal or selection favouring one subspecies over the other.

Recurrent specialization on a toxic fruit in an island Drosophila population

Significance Host plant specialization is a major cause of diversification in insects. The specialization of the fly Drosophila sechellia on the toxic fruits of noni has been a source of great scientific value, but selection is old enough that genetic variation does not seem useful in mapping the causative genes. On the island of Mayotte, we discovered a population of the related species Drosophila yakuba that is strongly associated with noni compared with generalist mainland populations. We then leveraged genomic variation to reconstruct the recent divergence history of this population and identify the potential targets of selection. Our top candidates included genes that confer tolerance to nonis toxin in D. sechellia. These findings establish a new model for recurrent ecological specialization. Recurrent specialization on similar host plants offers a unique opportunity to unravel the evolutionary and genetic mechanisms underlying dietary shifts. Recent studies have focused on ecological races belonging to the same species, but it is hard in many cases to untangle the role of adaptive introgression versus distinct mutations in facilitating recurrent evolution. We discovered on the island of Mayotte a population of the generalist fly Drosophila yakuba that is strictly associated with noni (Morinda citrifolia). This case strongly resembles Drosophila sechellia, a genetically isolated insular relative of D. yakuba whose intensely studied specialization on toxic noni fruits has always been considered a unique event in insect evolution. Experiments revealed that unlike mainland D. yakuba strains, Mayotte flies showed strong olfactory attraction and significant toxin tolerance to noni. Island females strongly discriminated against mainland males, suggesting that dietary adaptation has been accompanied by partial reproductive isolation. Population genomic analysis indicated a recent colonization (∼29 kya), at a time when year-round noni fruits may have presented a predictable resource on the small island, with ongoing migration after colonization. This relatively recent time scale allowed us to search for putatively adaptive loci based on genetic variation. Strong signals of genetic differentiation were found for several detoxification genes, including a major toxin tolerance locus in D. sechellia. Our results suggest that recurrent evolution on a toxic resource can involve similar historical events and common genetic bases, and they establish an important genetic system for the study of early stages of ecological specialization and speciation.

The Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome Reveals a Network of Epistatic Fitness Interactions

North American populations of Drosophila melanogaster derive from both European and African source populations, but despite their importance for genetic research, patterns of ancestry along their genomes are largely undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome, which may have implications for reference alignment, association mapping, and population genomic studies in Drosophila. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Combining my estimate of admixture timing with historical records, I provide the first estimate of natural generation time for this species (approximately 15 generations per year). Ancestry levels were found to vary strikingly across the genome, with less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes (e.g., circadian rhythm). An important role for natural selection during the admixture process was further supported by evidence that many unlinked pairs of loci showed a deficiency of Africa–Europe allele combinations between them. Numerous epistatic fitness interactions may therefore exist between African and European genotypes, leading to ongoing selection against incompatible variants. By focusing on hubs in this network of fitness interactions, I identified a set of interacting loci that include genes with roles in sensation and neuropeptide/hormone reception. These findings suggest that admixed D. melanogaster samples could become an important study system for the genetics of early-stage isolation between populations.

A Thousand Fly Genomes: An Expanded Drosophila Genome Nexus

The Drosophila Genome Nexus is a population genomic resource that provides D. melanogaster genomes from multiple sources. To facilitate comparisons across data sets, genomes are aligned using a common reference alignment pipeline which involves two rounds of mapping. Regions of residual heterozygosity, identity-by-descent, and recent population admixture are annotated to enable data filtering based on the user’s needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,121 wild-derived genomes. New additions include 305 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from recently-published data sets. We also provide an aligned D. simulans genome to facilitate divergence comparisons. This improved resource will broaden the range of population genomic questions that can addressed from multi-population allele frequencies and haplotypes in this model species. The larger set of genomes will also enhance the discovery of functionally relevant natural variation that exists within and between populations.

Spatially varying selection shapes life history clines among populations of Drosophila melanogaster from sub-Saharan Africa

Clines in life history traits, presumably driven by spatially varying selection, are widespread. Major latitudinal clines have been observed, for example, in Drosophila melanogaster, an ancestrally tropical insect from Africa that has colonized temperate habitats on multiple continents. Yet, how geographic factors other than latitude, such as altitude or longitude, affect life history in this species remains poorly understood. Moreover, most previous work has been performed on derived European, American and Australian populations, but whether life history also varies predictably with geography in the ancestral Afro‐tropical range has not been investigated systematically. Here, we have examined life history variation among populations of D. melanogaster from sub‐Saharan Africa. Viability and reproductive diapause did not vary with geography, but body size increased with altitude, latitude and longitude. Early fecundity covaried positively with altitude and latitude, whereas lifespan showed the opposite trend. Examination of genetic variance–covariance matrices revealed geographic differentiation also in trade‐off structure, and QST‐FST analysis showed that life history differentiation among populations is likely shaped by selection. Together, our results suggest that geographic and/or climatic factors drive adaptive phenotypic differentiation among ancestral African populations and confirm the widely held notion that latitude and altitude represent parallel gradients.

The Power of Natural Variation for Model Organism Biology

Genetic background effects have long been recognized and, in some cases studied, but they are often viewed as a nuisance by molecular biologists. We suggest that genetic variation currently represents a critical frontier for molecular studies. Human genetics has seen a surge of interest in genetic variation and its contributions to disease, but insights into disease mechanisms are difficult since information about gene function is lacking. By contrast, model organism genetics has excelled at revealing molecular mechanisms of cellular processes, but often de-emphasizes genetic variation and its functional consequences. We argue that model organism biology would benefit from incorporating natural variation, both to capture how well laboratory lines exemplify the species they represent and to inform on molecular processes and their variability. Such a synthesis would also greatly expand the relevance of model systems for studies of complex trait variation, including disease.

Epigenomic programming contributes to the genomic drift evolution of the F-Box protein superfamily in Arabidopsis

Significance Gene families significantly influence organismal diversity and adaptation, but how they evolved and are controlled is not fully clear. Using the Arabidopsis F-Box protein superfamily as a model, we show that both genomic and epigenomic forces are consequential with reversible, suppressive chromatin marks potentially helping dampen the adverse effects of altered gene dosage and the emergence of deleterious alleles. Such forces might be relevant to other highly polymorphic gene families impacted by genomic drift evolution. Comparisons within expanding sequence databases have revealed a dynamic interplay among genomic and epigenomic forces in driving plant evolution. Such forces are especially obvious within the F-Box (FBX) superfamily, one of the largest and most polymorphic gene families in land plants, where its frequent lineage-specific expansions and contractions provide an excellent model to assess how genetic variation impacted gene function before and after speciation. Previous phylogenetic comparisons based on orthology, diversity, and expression patterns identified three plant FBX groups—Common, Lineage-Specific, and Pseudo(genized)—whose emergences are consistent with genomic drift evolution. Here, we examined this variance within Arabidopsis thaliana by evaluating SNPs for all 877 FBX loci from 432 naturally occurring accessions and their relationships to variations in natural selection, expression, and DNA/histone methylation. In line with their phenotypic importance, Common FBX loci have low polymorphism but high deleterious mutation rates indicative of stringent functional constraints. In contrast, the Lineage-Specific and Pseudo groups are enriched in genes with basal expression and higher SNP density and more correlated with methylation marks (RNA-directed DNA methylation and histone H3K27 trimethylation) that promote transcriptional silencing. Taken together, we propose that reversible epigenomic modifications helped shape FBX gene evolution by transcriptionally suppressing the adverse effects of gene dosage imbalance and harmful FBX alleles that arise during genomic drift, while simultaneously allowing innovations to emerge through epigenomic reprogramming.