Academic journal article Genetics

Quantitative Trait Loci for Locomotor Behavior in Drosophila Melanogaster

Academic journal article Genetics

Quantitative Trait Loci for Locomotor Behavior in Drosophila Melanogaster

Article excerpt

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.

LOCOMOTION is an integral component of most animal behaviors: movement is required for localization of food and mates, escape from predators, defense of territory, and response to stress. Locomotor behavior can also be regarded as a major component of fitness, given its central role in survival and reproduction (GILCHRIST et al. 1997). Many human neurological diseases (e.g., Parkinson's disease and Huntington's disease) are associated with locomotor deficits, and hyperactivity and hypoactivity are, respectively, associated with activity disorders and depression (AMERICAN PSYCHIATRIC ASSOCIATION 1994). Locomotion is a complex behavior, and variation in nature is likely attributable to the joint segregation of multiple interacting quantitative trait loci (QTL), with effects that are sensitive to the environment. Thus, understanding the genetic architecture of locomotor behavior is important from the dual perspectives of evolutionary biology and human health. However, our current knowledge falls short of the level of detail with which we ultimately seek to describe variation in this trait: Which genes contribute to natural variation in locomotion? What are their homozygous, heterozygous, epistatic, and pleiotropic effects? How do these effects vary in a natural range of environments? And what are the molecular polymorphisms responsible for natural allelic variation? Although to date no complex trait in any organism has been dissected at this level of detail, the greatest opportunity for success will come from genetic analysis of model organisms with excellent genetic and genomic resources, such as Drosophila melanogaster. Further, basic biological processes, including development of the nervous system, are evolutionarily conserved between flies and mammals (ADAMS et al. 2000). Thus, the same genes affecting Drosophila locomotion may well be relevant in humans.

Indeed, Drosophila provides a model for several human neurodegenerative diseases with marked locomotor impairments. Parkinson's disease is the most common neurodegenerative movement disorder and is associated with progressive degeneration of nigrostriatal dopaminergic neurons and accumulation of Lewy bodies, neuronal cytoplasmic inclusions containing ubiquitinated proteins (OLANOW and TATTON 1999). Consistent with a causal role of dopamine in the pathogenesis of Parkinson's disease, treatment with the precursor L-dopa ameliorates the symptoms in early stages of the disease. Dopamine has also been implicated in locomotion of mice (ZHOU and PALMITER 1995) and Drosophila.

In Drosophila, tyrosine is converted to L-dopa by tyrosine hydroxylase (encoded by pale), which is then decarboxylated by Dopa decarboxylase (encoded by Dopa decarboxlyase, Ddc) to yield dopamine (MONASTIRIOTI 1999). …

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