Quantitative trait loci for locomotor behavior in Drosophila melanogaster

Abstract

Locomotion is an integral component of most animal behaviors and many human diseases and disorders are associated with locomotor deficits, but little is known about the genetic basis of natural variation in locomotor behavior. Locomotion is a complex trait, with variation attributable to the joint segregation of multiple interacting quantitative trait loci (QTL), with effects that are sensitive to the environment. We assessed variation in a component of locomotor behavior (locomotor reactivity) in a population of 98 recombinant inbred lines of Drosophila melanogaster and mapped four QTL affecting locomotor reactivity by linkage to polymorphic roo transposable element insertion sites. We used complementation tests of deficiencies to fine map these QTL to 12 chromosomal regions and complementation tests of mutations to identify 13 positional candidate genes affecting locomotor reactivity, including Dopa decarboxylase (Ddc), which catalyzes the final step in the synthesis of serotonin and dopamine. Linkage disequilibrium mapping in a population of 164 second chromosome substitution lines derived from a single natural population showed that polymorphisms at Ddc were associated with naturally occurring genetic variation in locomotor behavior. These data implicate variation in the synthesis of bioamines as a factor contributing to natural variation in locomotor reactivity.

Figure 1.—

Variation in locomotor reactivity for males (blue) and females (red). Mean reactivity scores are depicted for the parental strains, Ore-R and 2b, and for the mapping population of 98 RI lines.

Figure 2.—

QTL for locomotor reactivity. Triangles on the x-axis depict the locations of roo transposable element markers in centimorgans. The y-axis is the LR test statistic. The horizontal lines denote the LR statistics corresponding to permutation-derived experiment-wise 5% significance thresholds, shown separately for males and females.

Figure 3.—

High-resolution QTL mapping using complementation tests of deficiencies. Each horizontal bar shows the cytological breakpoints of the tested deficiencies (supplemental Table 1 at http://www.genetics.org/supplemental/). Red bars indicate deficiencies exhibiting quantitative failure to complement QTL affecting locomotor behavior, and blue bars indicate quantitative complementation. (A–D) The four genomic regions to which QTL affecting locomotor reactivity were mapped. The scale denotes sections and subsections of polytene chromosomes. (A) 1B–5F. (B) 23A–30C. (C) 29C–44F. (D) 97A–100F.

Figure 3.—

High-resolution QTL mapping using complementation tests of deficiencies. Each horizontal bar shows the cytological breakpoints of the tested deficiencies (supplemental Table 1 at http://www.genetics.org/supplemental/). Red bars indicate deficiencies exhibiting quantitative failure to complement QTL affecting locomotor behavior, and blue bars indicate quantitative complementation. (A–D) The four genomic regions to which QTL affecting locomotor reactivity were mapped. The scale denotes sections and subsections of polytene chromosomes. (A) 1B–5F. (B) 23A–30C. (C) 29C–44F. (D) 97A–100F.

Figure 3.—

High-resolution QTL mapping using complementation tests of deficiencies. Each horizontal bar shows the cytological breakpoints of the tested deficiencies (supplemental Table 1 at http://www.genetics.org/supplemental/). Red bars indicate deficiencies exhibiting quantitative failure to complement QTL affecting locomotor behavior, and blue bars indicate quantitative complementation. (A–D) The four genomic regions to which QTL affecting locomotor reactivity were mapped. The scale denotes sections and subsections of polytene chromosomes. (A) 1B–5F. (B) 23A–30C. (C) 29C–44F. (D) 97A–100F.

Figure 3.—

High-resolution QTL mapping using complementation tests of deficiencies. Each horizontal bar shows the cytological breakpoints of the tested deficiencies (supplemental Table 1 at http://www.genetics.org/supplemental/). Red bars indicate deficiencies exhibiting quantitative failure to complement QTL affecting locomotor behavior, and blue bars indicate quantitative complementation. (A–D) The four genomic regions to which QTL affecting locomotor reactivity were mapped. The scale denotes sections and subsections of polytene chromosomes. (A) 1B–5F. (B) 23A–30C. (C) 29C–44F. (D) 97A–100F.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 4.—

Mutant complementation tests. Means and standard errors of locomotor reactivity (in seconds, y-axis) are given for the genes that exhibited failure to complement Ore-R and 2b alleles, separately for crosses to mutants (M) and balancers (B) (x-axis). Males (blue) from the crosses to Ore-R. Females (pink) from the crosses to Ore-R. Males (gold) from the crosses to 2b. Females (green) from the crosses to 2b. (A) nob^KS49. (B) tutl⁰¹⁰⁸⁵. (C) Trf¹. (D) crol⁰⁴⁴¹⁸. (E) stc⁰⁵⁴⁴¹. (F) Catsup¹. (G) Lim3¹. (H) Ddc²⁷. (I) drl². (J) tyr1¹. (K) Acon⁰⁷⁰⁵⁴. (L) tsh⁰⁴³¹⁹. (M) Dr¹.

Figure 5.—

Association of polymorphic markers at Ddc with variation in locomotor reactivity among 164 second chromosome substitution lines. The 36 polymorphic markers at Ddc are given on the x-axis, and P-values, transformed to log(1/P), from the ANOVA tests of association of the markers with locomotor reactivity are given on the y-axis. The red horizontal line denotes the nominal 5% significance level. Marker T1042G, denoted by *, is formally significant on the basis of a permutation test for individual makers, as well as the Bonferroni-corrected experiment-wise 5% significance level.