Biology subjects

John E Pool

Publications and source records attributed to John E Pool.

5 recordsLinked to original sources

bioRxiv2016

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 users needs. Here, we present a significant expansion of the Drosophila Genome Nexus, which brings the current data object to a total of 1,122 wild-derived genomes. New additions include 306 previously unpublished genomes from inbred lines representing six population samples in Egypt, Ethiopia, France, and South Africa, along with another 193 genomes added from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.

Genomics↗

bioRxiv2016

Parallel Evolution of Cold Tolerance Within Drosophila melanogaster

Drosophila melanogaster originated in tropical Africa before expanding into strikingly different temperate climates in Eurasia and beyond. Here, we show that elevated cold tolerance has arisen at least three times within this species: beyond the well-studied non-African case, we show that populations from the highlands of Ethiopia and South Africa have significantly increased cold tolerance as well. We observe greater cold tolerance in outbred versus inbred flies, but only in populations with higher inversion frequencies. Each cold-adapted population shows lower inversion frequencies than a closely-related warm-adapted population, suggesting that inversion frequencies may decrease with altitude in addition to latitude. Using the FST-based \"Population Branch Excess\" statistic (PBE), we found only limited evidence for parallel genetic differentiation at the scale of ~4 kb windows, specifically between Ethiopian and South African cold-adapted populations. And yet, when we looked for single nucleotide polymorphisms (SNPs) with codirectional frequency change in two or three cold-adapted populations, strong genomic enrichments were observed from all comparisons. These findings could reflect an important role for selection on standing genetic variation leading to \"soft sweeps\". One SNP showed sufficient codirectional frequency change in all cold-adapted populations to achieve experiment-wide significance: an intronic variant in the synaptic gene Prosap. More generally, proteins involved in neurotransmission were enriched as potential targets of parallel adaptation. The ability to study cold tolerance evolution in a parallel framework will enhance this classic study system for climate adaptation.

Evolutionary Biology↗

bioRxiv2016

Genetic Mapping by Bulk Segregant Analysis in Drosophila: Experimental Design and Simulation-Based Inference

Identifying the genomic regions that underlie complex phenotypic variation is a key challenge in modern biology. Many approaches to quantitative trait locus mapping in animal and plant species suffer from limited power and genomic resolution. Here, I investigate whether bulk segregant analysis (BSA), which has been successfully applied for yeast, may have utility in the genomic era for trait mapping in Drosophila (and other organisms that can be experimentally bred in similar numbers). I perform simulations to investigate the statistical signal of a quantitative trait locus (QTL) in a wide range of BSA and introgression mapping (IM) experiments. BSA consistently provides more accurate mapping signals than IM (in addition to allowing the mapping of multiple traits from the same experimental population). The performance of BSA and IM is maximized by having multiple independent crosses, more generations of interbreeding, larger numbers of breeding individuals, and greater genotyping effort, but is less affected by the proportion of individuals selected for phenotypic extreme pools. I also introduce a prototype analysis method for Simulation-based Inference for BSA Mapping (SIBSAM). This method identifies significant QTLs and estimates their genomic confidence intervals and relative effect sizes. Importantly, it also tests whether overlapping peaks should be considered as two distinct QTLs. This approach will facilitate improved trait mapping in Drosophila and other species for which hundreds or thousands of offspring (but not millions) can be studied.

Genetics↗

bioRxiv2016

Oligogenic Adaptation, Soft Sweeps, and Parallel Melanic Evolution in Drosophila melanogaster

Unraveling the genetic architecture of adaptive phenotypic divergence is a fundamental quest in evolutionary biology. In Drosophila melanogaster, high-altitude melanism has evolved in separate mountain ranges in sub-Saharan Africa, potentially as an adaptation to UV intensity. We investigated the genetic basis of this melanism in three populations using a new bulk segregant analysis mapping method. Although hundreds of genes are known to affect cuticular pigmentation in D. melanogaster, we identified only 19 distinct QTLs from 9 mapping crosses, with several QTL peaks being shared among two or all populations. Surprisingly, we did not find wide signals of genetic differentiation (Fst) between lightly and darkly pigmented populations at these QTLs, in spite of the pronounced phenotypic difference in pigmentation. Instead, we found small numbers of highly differentiated SNPs at the probable causative genes. A simulation analysis showed that these patterns of polymorphism are consistent with selection on standing genetic variation (leading to \"soft sweeps\"). Our results thus support a role for oligogenic selection on standing genetic variation in driving parallel ecological adaptation.

Genetics↗

bioRxiv2015

Natural Selection Shapes the Mosaic Ancestry of the Drosophila Genetic Reference Panel and the D. melanogaster Reference Genome

North American populations of Drosophila melanogaster are thought to derive from both European and African source populations, but despite their importance for genetic research, patterns of admixture along their genomes are essentially undocumented. Here, I infer geographic ancestry along genomes of the Drosophila Genetic Reference Panel (DGRP) and the D. melanogaster reference genome. Overall, the proportion of African ancestry was estimated to be 20% for the DGRP and 9% for the reference genome. Based on the size of admixture tracts and the approximate timing of admixture, I estimate that the DGRP population underwent roughly 13.9 generations per year. Notably, ancestry levels varied strikingly among genomic regions, with significantly less African introgression on the X chromosome, in regions of high recombination, and at genes involved in specific processes such as circadian rhythm. An important role for natural selection during the admixture process was further supported by a genome-wide signal of ancestry disequilibrium, in that many between-chromosome pairs of loci showed a deficiency of Africa-Europe allele combinations. These results support the hypothesis that admixture between partially genetically isolated Drosophila populations led to natural selection against incompatible genetic variants, and that this process is ongoing. The ancestry blocks inferred here may be relevant for the performance of reference alignment in this species, and may bolster the design and interpretation of many population genetic and association mapping studies.

Evolutionary Biology↗