The loci of behavioral evolution: Fas2 and tilB underlie differences in pupation site choice behavior between Drosophila melanogaster and D. simulans

AbstractThe recent boom in genotype-phenotype studies has led to a greater understanding of the genetic architecture of a variety of traits. Among these traits, however, behaviors are still lacking, perhaps because they are complex and environmentally sensitive phenotypes, making them difficult to measure reliably for association studies. Here, we aim to fill this gap in knowledge with the results of a genetic screen for a complex behavioral difference, pupation site choice, between Drosophila melanogaster and D. simulans. In this study, we demonstrate a significant contribution of the X chromosome to the difference in pupation site choice behavior between these species. Using a panel of X-chromosome deletions, we screened the majority of the X chromosome for causal loci, and identified two regions that explain a large proportion of the X-effect. We then used gene disruptions and RNAi to demonstrate the substantial effects of a single gene within each region: Fas2 and tilB. Finally, we show that differences in tilB expression underlie species differences in pupation site choice behavior, and that generally, pupation site choice behavior appears to be correlated with relative expression of this gene. Our results suggest that even complex, environmentally sensitive behaviors may evolve through changes to loci with large phenotypic effects.Author summaryBehaviors are complex traits that involve sensory detection, higher level processing, and a coordinated output by the nervous system. This level of processing is highly susceptible to environmentally induced variation. Because of their complexity and sensitivity, behaviors are difficult to study; as a result, we have very little understanding of the genes involved in behavioral variation. In this study, we use common laboratory fruit fly model, Drosophila, to address this gap and dissect the genetic underpinnings of an environmentally sensitive behavior that differs between species. We find that a significant amount of the phenotypic difference between species is explained by a single chromosome. We further show that just two genes on this chromosome account for a large majority of its effect, suggesting that the genetic basis of complex behavioral evolution may be simpler than anticipated. For one of these genes, we show that a species-level difference in gene expression is associated with the difference in behavior. Our results contribute to a growing number of studies identifying the genetic components of behavior. Ultimately, we hope to use these data to better predict the number, types, and effects of genetic mutations necessary for complex behaviors to evolve.

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The Loci of Behavioral Evolution: Evidence That Fas2 and tilB Underlie Differences in Pupation Site Choice Behavior between Drosophila melanogaster and D. simulans

Molecular Biology and Evolution ◽

10.1093/molbev/msz274 ◽

2019 ◽

Vol 37 (3) ◽

pp. 864-880

Author(s):

Alison Pischedda ◽

Michael P Shahandeh ◽

Thomas L Turner

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Related Species ◽

Choice Behavior ◽

Genetic Basis ◽

Association Studies ◽

Single Gene ◽

Closely Related Species ◽

Environmentally Sensitive ◽

Pupation Site

Abstract The behaviors of closely related species can be remarkably different, and these differences have important ecological and evolutionary consequences. Although the recent boom in genotype–phenotype studies has led to a greater understanding of the genetic architecture and evolution of a variety of traits, studies identifying the genetic basis of behaviors are, comparatively, still lacking. This is likely because they are complex and environmentally sensitive phenotypes, making them difficult to measure reliably for association studies. The Drosophila species complex holds promise for addressing these challenges, as the behaviors of closely related species can be readily assayed in a common environment. Here, we investigate the genetic basis of an evolved behavioral difference, pupation site choice, between Drosophila melanogaster and D. simulans. In this study, we demonstrate a significant contribution of the X chromosome to the difference in pupation site choice behavior between these species. Using a panel of X-chromosome deficiencies, we screened the majority of the X chromosome for causal loci and identified two regions associated with this X-effect. We then collect gene disruption and RNAi data supporting a single gene that affects pupation behavior within each region: Fas2 and tilB. Finally, we show that differences in tilB expression correlate with the differences in pupation site choice behavior between species. This evidence associating two genes with differences in a complex, environmentally sensitive behavior represents the first step toward a functional and evolutionary understanding of this behavioral divergence.

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Specificity of Chromosome Damage Caused by the Rex Element of Drosophila melanogaster

Genetics ◽

10.1093/genetics/144.1.109 ◽

1996 ◽

Vol 144 (1) ◽

pp. 109-115 ◽

Cited By ~ 1

Author(s):

Leonard G Robbins

Keyword(s):

Drosophila Melanogaster ◽

Early Development ◽

X Chromosome ◽

Ribosomal Rna ◽

Chromosome Damage ◽

Genetic Element ◽

Single Chromosome ◽

Experimental Cross ◽

Rdna Array ◽

Early Embryos

Abstract Rex is a multicopy genetic element that maps within an X-linked ribosomal RNA gene (rDNA) array of D. melanogaster. Acting maternally, Rex causes recombination between rDNA arrays in a few percent of early embryos. With target chromosomes that contain two rDNA arrays, the exchanges either delete all of the material between the two arrays or invert the entire intervening chromosomal segment. About a third of the embryos produced by Rex homozygotes have cytologically visible chromosome damage, nearly always involving a single chromosome. Most of these embryos die during early development, displaying a characteristic apoptosis-like phenotype. An experiment that tests whether the cytologically visible damage is rDNA-specific is reported here. In this experiment, females heterozygous for Rex and an rDNA-deficient X chromosome were crossed to males of two genotypes. Some of the progeny from the experimental cross entirely lacked rDNA, while all of the progeny from the control cross had at least one rDNA array. A significantly lower frequency of early-lethal embryos in the experimental cross, proportionate to the fraction of rDNA-deficient embryos, demonstrates that Rex preferentially damages rDNA.

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Patterns of DNA Variability at X-Linked Loci in Mus domesticus

Genetics ◽

10.1093/genetics/147.3.1303 ◽

1997 ◽

Vol 147 (3) ◽

pp. 1303-1316

Author(s):

Michael W Nachman

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

House Mouse ◽

Recombination Rate ◽

Nucleotide Diversity ◽

Mus Domesticus ◽

Substantial Variation ◽

Intraspecific Polymorphism ◽

Recombination Rates ◽

Interspecific Divergence

Introns of four X-linked genes (Hprt, Plp, Glra2, and Amg) were sequenced to provide an estimate of nucleotide diversity at nuclear genes within the house mouse and to test the neutral prediction that the ratio of intraspecific polymorphism to interspecific divergence is the same for different loci. Hprt and Plp lie in a region of the X chromosome that experiences relatively low recombination rates, while Glra2 and Amg lie near the telomere of the X chromosome, a region that experiences higher recombination rates. A total of 6022 bases were sequenced in each of 10 Mus domesticus and one M. caroli. Average nucleotide diversity (π) for introns within M. domesticus was quite low (π = 0.078%). However, there was substantial variation in the level of heterozygosity among loci. The two telomeric loci, Glra2 and Amg, had higher ratios of polymorphism to divergence than the two loci experiencing lower recombination rates. These results are consistent with the hypothesis that heterozygosity is reduced in regions with lower rates of recombination, although sampling of additional genes is needed to establish whether there is a general correlation between heterozygosity and recombination rate as in Drosophila melanogaster.

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SITE-SPECIFIC INSTABILITY IN DROSOPHILA MELANOGASTER: EVIDENCE FOR TRANSPOSITION OF DESTABILIZING ELEMENT

Genetics ◽

10.1093/genetics/101.3-4.461 ◽

1982 ◽

Vol 101 (3-4) ◽

pp. 461-476

Author(s):

Todd R Laverty ◽

J K Lim

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Lethal Mutation ◽

Chromosome Rearrangements ◽

Chromosome Break ◽

Secondary Mutation ◽

X Chromosomes ◽

Site Specific ◽

Normal Sequence ◽

Lethal Mutations

ABSTRACT In this study, we show that at least one lethal mutation at the 3F-4A region of the X chromosome can generate an array of chromosome rearrangements, all with one chromosome break in the 3F-4A region. The mutation at 3F-4A (secondary mutation) was detected in an X chromosome carrying a reverse mutation of an unstable lethal mutation, which was mapped in the 6F1-2 doublet (primary mutation). The primary lethal mutation at 6F1-2 had occurred in an unstable chromosome (Uc) described previously (Lim 1979). Prior to reversion, the 6F1-2 mutation had generated an array of chromosome rearrangements, all having one break in the 6F1-2 doublet (Lim 1979, 1980). In the X chromosomes carrying the 3F-4A secondary lethal mutation the 6F1-2 doublet was normal and stable, as was the 3F-4A region in the X chromosome carrying the primary lethal mutation. The disappearance of the instability having a set of genetic properties at one region (6F1-2) accompanied by its appearance elsewhere in the chromosome (3F-4A) implies that a transposition of the destabilizing element took place. The mutant at 3F-4A and other secondary mutants exhibited all but one (reinversion of an inversion to the normal sequence) of the eight properties of the primary lethal mutations. These observations support the view that a transposable destabilizing element is responsible for the hypermutability observed in the unstable chromosome and its derivaties.

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Hybrid dysgenesis-induced quantitative variation on the X chromosome of Drosophila melanogaster.

Genetics ◽

10.1093/genetics/124.3.627 ◽

1990 ◽

Vol 124 (3) ◽

pp. 627-636

Author(s):

C Q Lai ◽

T F Mackay

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Quantitative Traits ◽

Natural Populations ◽

Quantitative Variation ◽

Hybrid Dysgenesis ◽

X Chromosomes ◽

Bristle Number ◽

Seven Generations ◽

Polygenic Variation

Abstract To determine the ability of the P-M hybrid dysgenesis system of Drosophila melanogaster to generate mutations affecting quantitative traits, X chromosome lines were constructed in which replicates of isogenic M and P strain X chromosomes were exposed to a dysgenic cross, a nondysgenic cross, or a control cross, and recovered in common autosomal backgrounds. Mutational heritabilities of abdominal and sternopleural bristle score were in general exceptionally high-of the same magnitude as heritabilities of these traits in natural populations. P strain chromosomes were eight times more mutable than M strain chromosomes, and dysgenic crosses three times more effective than nondysgenic crosses in inducing polygenic variation. However, mutational heritabilities of the bristle traits were appreciable for P strain chromosomes passed through one nondysgenic cross, and for M strain chromosomes backcrossed for seven generations to inbred P strain females, a result consistent with previous observations on mutations affecting quantitative traits arising from nondysgenic crosses. The new variation resulting from one generation of mutagenesis was caused by a few lines with large effects on bristle score, and all mutations reduced bristle number.

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A nonparametric test for association with multiple loci in the retrospective case-control study

Statistical Methods in Medical Research ◽

10.1177/0962280219842892 ◽

2019 ◽

Vol 29 (2) ◽

pp. 589-602

Author(s):

Chan Wang ◽

Shufang Deng ◽

Leiming Sun ◽

Liming Li ◽

Yue-Qing Hu

Keyword(s):

Rare Variants ◽

Association Studies ◽

Nonparametric Test ◽

Case Control ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Retrospective Case ◽

Multiple Loci ◽

Common Diseases ◽

The Difference

The genome-wide association studies aim at identifying common or rare variants associated with common diseases and explaining more heritability. It is well known that common diseases are influenced by multiple single nucleotide polymorphisms (SNPs) that are usually correlated in location or function. In order to powerfully detect association signals, it is highly desirable to take account of correlations or linkage disequilibrium (LD) information among multiple SNPs in testing for association. In this article, we propose a test SLIDE that depicts the difference of the average multi-locus genotypes between cases and controls and derive its variance–covariance matrix in the retrospective design. This matrix is composed of the pairwise LD between SNPs. Thus SLIDE can borrow the strength from an external database in the population of interest with a few thousands to hundreds of thousands individuals to improve the power for detecting association. Extensive simulations show that SLIDE has apparent superiority over the existing methods, especially in the situation involving both common and rare variants, both protective and deleterious variants. Furthermore, the efficiency of the proposed method is demonstrated in the application to the data from the Wellcome Trust Case Control Consortium.

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Recombination in the X-chromosome in hybrid females with and without a marked centromere from three inbred lines of Drosophila melanogaster

Hereditas ◽

10.1111/j.1601-5223.1985.tb00470.x ◽

2008 ◽

Vol 102 (1) ◽

pp. 89-97 ◽

Cited By ~ 4

Author(s):

STAFFAN LAKE

Keyword(s):

Drosophila Melanogaster ◽

X Chromosome ◽

Inbred Lines

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Cytogenetic and complementation analyses of recessive lethal mutations induced in the X chromosome of Drosophila by three alkylating agents

Genetics Research ◽

10.1017/s0016672300015020 ◽

1974 ◽

Vol 24 (1) ◽

pp. 1-10 ◽

Cited By ~ 32

Author(s):

J. K. Lim ◽

L. A. Snyder

Keyword(s):

Drosophila Melanogaster ◽

Salivary Gland ◽

X Chromosome ◽

Alkylating Agents ◽

Complementation Analysis ◽

Ethyl Methanesulphonate ◽

Induced Mutations ◽

Recessive Lethal ◽

Lethal Mutations

SUMMARYSalivary-gland chromosomes of 54 methyl methanesulphonate- and 50 triethylene melamine-induced X-chromosome recessive lethals in Drosophila melanogaster were analysed. Two of the lethals induced by the mono-functional agent and 11 of those induced by the polyfunctional agent were found to be associated with detectable aberrations. A complementation analysis was also done on 82 ethyl methanesulphonate- and 34 triethylene melamine-induced recessive lethals in the zeste-white region of the X chromosome. The EMS-induced lethals were found to represent lesions affecting only single cistrons. Each of the 14 cistrons in the region known to mutate to a lethal state was represented by mutant alleles, but in widely different frequencies. Seven of the TEM-induced lethals were associated with deletions, only one of which had both breakpoints within the mapped region. Twenty-six of the 27 mutations in which only single cistrons were affected were mapped to 7 of the 14 known loci. One TEM- and two EMS-induced mutations were alleles representing a previously undetected locus in the zeste-white region.

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