Copy Number Variation and Transposable Elements Feature in Recent, Ongoing Adaptation at the Cyp6g1 Locus

The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ∼16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession

Spliced DNA sequences in the Paramecium germline: their properties and evolutionary potential. Genome Biol

ABSTRACT Despite playing a crucial role in germline-soma differentiation, the evolutionary significance of developmentally regulated genome rearrangements (DRGRs) has received scant attention. An example of DRGR is DNA splicing, a process that removes segments of DNA interrupting genic and/or intergenic sequences. Perhaps best known for shaping immune-system genes in vertebrates, DNA splicing plays a central role in the life of ciliated protozoa, where thousands of germline DNA segments are eliminated after sexual reproduction to regenerate a functional somatic genome. Here, we identify and chronicle the properties of 5,286 sequences that putatively undergo DNA splicing (i.e., Internal Eliminated Sequences or IESs) across the genomes of three closely related species of the ciliate Paramecium (P. tetraurelia, P. biaurelia, and P. sexaurelia). The study reveals that these putative IESs share several physical characteristics. While our results are consistent with excision events being largely conserved between species, episodes of differential IES retention/excision occur, may have a recent origin, and frequently involve coding regions. Our findings indicate interconversion between somatic-often coding-DNA sequences and noncoding IESs, and provide insights into the role of DNA splicing in creating potentially functional genetic innovation

Current research on the influence of establishing operations on behavior in applied settings.

This article provides commentary on research published in the special section of the Journal of Applied Behavior Analysis devoted to establishing operations (EOs). Three major themes are highlighted: (a) identification of the influence of EOs on behavior in applied settings, (b) the use of EO manipulation as an assessment tool, and (c) the development of interventions based on the alteration of EO influences. Methodological issues pertaining to research on EOs are addressed, and suggestions for future investigation are provided

Cortical Dysplasia, Genetic Abnormalities and Neurocutaneous Syndromes.

Cortical dysplasia (CD) represents a common neuropathologic substrate of pediatric epilepsy, one frequently encountered in surgical resection specimens from infants and children with intractable seizure disorders, including infantile spasms. Severe CD shows similarities to structural features noted in tubers from individuals with tuberous sclerosis (TSC). The latter disorder, one with neurocutaneous and visceral manifestations, results from mutations in one of two recently cloned genes, TSC1 or TSC2, which encode (respectively) the proteins hamartin and tuberin. There is circumstantial evidence that both proteins may influence cell growth and differentiation, specifically that they may represent growth suppressors. Neither protein has a defined role in brain development. We discuss and illustrate neuropathologic features of both CD and TSC, and discuss the patterns and time course of hamartin/tuberin expression in normal brain, CD and TSC. Other recently cloned genes associated with cortical malformations encompassed by the term CD are briefly described

Assessment of preference for varied versus constant reinforcers.

One method that has been demonstrated to improve the effectiveness of reinforcement is stimulus (reinforcer) variation (Egel, 1980). Egel found that bar pressing increased and responding occurred more rapidly during varied reinforcement than during constant reinforcement when identical stimuli were used across phases for 10 individuals with autism. The purpose of the current investigation was to assess the preferences of 7 individuals for varied presentation of slightly lower quality stimuli relative to constant access to the highest quality stimulus. Varied presentation was preferred over constant reinforcer presentation with 4 participants, and the opposite was true for 2 participants. One participant did not demonstrate a preference. These results suggest that stimulus variation may allow less preferred reinforcers to compete effectively with a more highly preferred reinforcer for some individuals

Hamartin Expression and Interaction with Tuberin in Tumor Cell Lines and Primary Cultures.

Tuberous sclerosis (TSC) is a neurocutaneous disorder characterized by multi-system hamartomatous lesions, and results from a mutation in TSC1, that encodes hamartin, or TSC2, that encodes tuberin. We have examined hamartin expression in a diverse range of human and rat cell lines and primary cultured cells derived from tissues that express hamartin in vivo. Strong hamartin signal was detected in every cell line of human origin examined, representing neuronal, epithelial, lymphoid, renal, vascular smooth muscle, liver, and prostatic cells. Primary cell cultures of oligodendroglioma, meningioma, and glioblastoma multiforme origin were also found to express hamartin. Hamartin was also detected in the rat PC12 cell line, as well as purified primary cultures of rat cortical neurons, astrocytes, and oligodendroglia, with a stronger signal found in astrocytes. Using co-immunoprecipitation, we have also confirmed the physical interaction of tuberin and hamartin in a diverse range of human and rat cell types. These findings demonstrate that hamartin is widely expressed in human and rat cell lines and cultures, and demonstrate that hamartin expression is not lost during the establishment of tumor cell lines or primary cultures. This suggests that the cell lines and cultures studied may serve as useful in vitro models for biochemical investigations involving hamartin and tuberin both individually and as a complex, as well as studies to elucidate the mechanisms underlying the organ-specific pathology of TSC

The effects of the stimulus-reinforcer correlation in a discrete-trials IRT>t procedure

The correlation between a keylight and food in a discrete-trials, interresponse-time-greater-than 6-sec (IRT>6-sec) procedure was varied by manipulating the rate of response-independent food presentation in the intertrial interval. When the correlation was positive, the rates of pecking in the IRT>6-sec condition were high and food was obtained on only about 5% of the trials. Likewise, responding was maintained at a high rate in yoked birds that received the same presentations of the light and food as the birds in the IRT>6-sec condition. When the rate of reinforcement between trials was equated to or made greater than the rate of reinforcement within trials, the response rate decreased for all birds, and those decreases were considerably larger for the yoked birds. However, the percentage of trials in which reinforced responses occurred under the IRT>6-sec procedure did not increase substantially when the light and food were either uncorrelated or negatively correlated. The percentage of trials in which a reinforcer was obtained increased when the keylight was left on continuously and the discriminative stimulus was not presented on the key. The results show that the stimulus-reinforcer correlation affects responding in the discrete-trials IRT>6-sec procedure, but that the effects of the stimulus-reinforcer correlation vary as a function of whether reinforcement is response-dependent or response-independent. The differences between the effects of response-independent and response-dependent pairings and nonpairings of the light and food are best accounted for in terms of differences in the control of responding by background stimuli