The genetic basis ofDrosophila melanogasterdefense againstBeauveria bassianaexplored through evolve and resequence and quantitative trait locus mapping

Abstract

Many of the molecular mechanisms for antifungal immunity in Drosophila melanogaster have been defined, but relatively little is known about the genetic basis for variation in antifungal immunity in natural populations. Using two population genetic approaches, Quantitative Trait Locus (QTL) Mapping and Evolve and Resequence (E&R), we explored the genetics underlying D. melanogaster immune defense against infection with the fungus Beauveria bassiana. Immune defense was highly variable both in the recombinant inbred lines from the Drosophila Synthetic Population Resource used for our QTL Mapping and in the synthetic outbred populations used in our E&R study. Survivorship of infection improved dramatically over just 10 generations in the E&R study, and continued to increase for an additional 9 generations, revealing a trade-off with uninfected longevity. Populations selected for increased defense against B. bassiana evolved cross resistance to a second, distinct B. bassiana strain but not to bacterial pathogens. The QTL mapping study revealed that sexual dimorphism in defense depends on host genotype, and the E&R study indicated that dimorphism also depends on the specific pathogen to which the host is exposed. Both the QTL Mapping and E&R experiments generated lists of potentially causal candidate genes, although these lists were non-overlapping.

Adaptation in Outbred Sexual Yeast is Repeatable, Polygenic and Favors Rare Haplotypes

“…The bulk of previous E&R work in Drosophila has been carried out for fewer than 100 generations ( Orozco-terWengel et al 2012 ; Remolina et al 2012 ; Turner and Miller 2012 ; Huang et al 2014 ; Jalvingh et al 2014 ; Martins et al 2014 ; Tobler et al 2014 ; Franssen et al 2015 ; Jha et al 2015 ; Barghi et al 2017 ; Griffin et al 2017 ; Michalak et al 2017 ; Hardy et al 2018 ; Barghi et al 2019 ; Kelly and Hughes 2019 ; Sørensen et al 2020 ; Shahrestani et al 2021 ), with a handful of studies carried out for between 100 to 200 generations ( Turner et al 2011 ; Zhou et al 2011 ; Hoedjes et al 2019 ; Iranmehr et al 2021 ; Kawecki et al 2021 ) and only a few studies maintained for between 400 to greater than 900 generations ( Burke et al 2010 ; Phillips et al 2016 , 2018 ). Minimum census population sizes in these studies have ranged from hundreds to greater than 2,000 individuals ( Shahrestani et al 2021 ), with this work maintaining effective population sizes likely one to two orders of magnitude greater. The majority of studies in flies have evolved 2–5 replicate populations under 2–3 selection regimens, with the exception of a recent study in D. simulans which used 10 replicates ( Barghi et al 2019 ) as well as a recent study in D melanogaster which used 6 replicates ( Kawecki et al 2021 ).…”

“…Long-term adaptation is highly polygenic: A large number of studies in flies claim that adaptation in outbred sexuals is highly polygenic, with many loci throughout the genome responding to selection ( Clark et al 2007 ; Coop et al 2009 ; Burke et al 2010 ; Turner et al 2011 ; Orozco-terWengel et al 2012 ; Remolina et al 2012 ; Turner and Miller 2012 ; Chandler 2014 ; Huang et al 2014 ; Tobler et al 2014 ; Jha et al 2015 ; Kang et al 2016 ; Phillips et al 2016 ; Barghi et al 2017 ; Griffin et al 2017 ; Hardy et al 2018 ; Barghi et al 2019 ; Hoedjes et al 2019 ; Sørensen et al 2020 ; Kawecki et al 2021 ; Shahrestani et al 2021 ; Tusso et al 2021 ), but to some extent the inference of polygenicity is based on a visual inspection of Manhattan plots. Very few studies attempt to estimate the minimum number of factors consistent with observed results .…”

Adaptation in outbred sexual yeast is repeatable, polygenic, and favors rare haplotypes

“…Here, we employ 18 founders, still far fewer than fly experiments, but much more variation than previous budding yeast E&R experiments. The bulk of previous E&R work in Drosophila has been carried out for fewer than 100 generations (Barghi et al, 2017;Barghi et al, 2019;Franssen et al, 2015;Griffin et al, 2017;Hardy et al, 2018;Huang et al, 2014;Jalvingh et al, 2014;Jha et al, 2015;Kelly & Hughes, 2019;Martins et al, 2014;Michalak et al, 2017;Orozco-terWengel et al, 2012;Remolina et al, 2012;Shahrestani et al, 2021;Sørensen et al, 2020;Tobler et al, 2014;Turner & Miller, 2012), with a handful of studies carried out for between 100 to 200 generations (Hoedjes et al, 2019;Iranmehr et al, 2021;Kawecki et al, 2021;Turner et al, 2011;Zhou et al, 2011) and only a few studies maintained for between 400 to greater than 900 generations (Burke et al, 2010;Phillips et al, 2016Phillips et al, , 2018. Minimum census population sizes in these studies have ranged from hundreds to greater than two thousand individuals (Shahrestani et al, 2021).…”

“…A large number of studies in flies have claimed that adaptation in outbred sexuals is highly polygenic, with many loci throughout the genome responding to selection (Barghi et al, 2017;Barghi et al, 2019;Burke et al, 2010;Chandler, 2014;Clark et al, 2007;Coop et al, 2009;Griffin et al, 2017;Hardy et al, 2018;Hoedjes et al, 2019;Huang et al, 2014;Jha et al, 2015;Kang et al, 2016;Kawecki et al, 2021;Orozco-terWengel et al, 2012;Phillips et al, 2016;Remolina et al, 2012;Shahrestani et al, 2021;Sørensen et al, 2020;Tobler et al, 2014;Turner et al, 2011;Turner & Miller, 2012;Tusso et al, 2021), but to some extent the inference of polygenicity is based on a visual inspection of Manhattan plots. Very few studies attempt to estimate the minimum number of factors consistent with observed results.…”

“…E&R experiments are typically initiated from an outbred base population and then changes in the frequency of SNPs observed following adaptation (Barghi et al, 2017;Barghi et al, 2019;Burke et al, 2010;Franssen et al, 2015;Griffin et al, 2017;Hardy et al, 2018;Huang et al, 2014;Jalvingh et al, 2014;Jha et al, 2015;Kelly & Hughes, 2019;Martins et al, 2014;Michalak et al, 2017;Orozco-terWengel et al, 2012;Phillips et al, 2016Phillips et al, , 2018Remolina et al, 2012;Shahrestani et al, 2021;Sørensen et al, 2020;Tobler et al, 2014;Turner & Miller, 2012;Hoedjes et al, 2019;Iranmehr et al, 2021;Kawecki et al, 2021;Turner et al, 2011;Zhou et al, 2011). Such studies have several strengths, but it is difficult to distinguish SNPs that are drivers versus responders.…”