James R. Morris

Transvection and other homology effects.

The presence of homologous nucleic acid sequences can exert profound effects on chromosomal and gene function in a wide range of organisms. These homology effects reveal remarkable forms of regulation as well as suggest possible avenues for the development of new technologies.

Effects of Chromosomal Rearrangements on Transvection at the yellow Gene of Drosophila melanogaster

Homologous chromosomes are paired in somatic cells of Drosophila melanogaster. This pairing can lead to transvection, which is a process by which the proximity of homologous genes can lead to a change in gene expression. At the yellow gene, transvection is the basis for several examples of intragenic complementation involving the enhancers of one allele acting in trans on the promoter of a paired second allele. Using complementation as our assay, we explored the chromosomal requirements for pairing and transvection at yellow. Following a protocol established by Ed Lewis, we generated and characterized chromosomal rearrangements to define a region in cis to yellow that must remain intact for complementation to occur. Our data indicate that homolog pairing at yellow is efficient, as complementation was disrupted only in the presence of chromosomal rearrangements that break ≤650 kbp from yellow. We also found that three telomerically placed chromosomal duplications, containing ∼700 or more kbp of the yellow genomic region, are able to alter complementation at yellow, presumably through competitive pairing interactions. These results provide a formal demonstration of the pairing-dependent nature of yellow transvection and suggest that yellow pairing, as measured by transvection, reflects the extent of contiguous homology flanking the locus.

Restoration of Topoisomerase 2 Function by Complementation of Defective Monomers in Drosophila

Type II topoisomerases are essential ATP-dependent homodimeric enzymes required for transcription, replication, and chromosome segregation. These proteins alter DNA topology by generating transient enzyme-linked double-strand breaks for passage of one DNA strand through another. The central role of type II topoisomerases in DNA metabolism has made these enzymes targets for anticancer drugs. Here, we describe a genetic screen that generated novel alleles of Drosophila Topoisomerase 2 (Top2). Fifteen alleles were obtained, resulting from nonsense and missense mutations. Among these, 14 demonstrated recessive lethality, with one displaying temperature-sensitive lethality. Several newly generated missense alleles carry amino acid substitutions in conserved residues within the ATPase, Topoisomerase/Primase, and Winged helix domains, including four that encode proteins with alterations in residues associated with resistance to cancer chemotherapeutics. Animals lacking zygotic Top2 function can survive to pupation and display reduced cell division and altered polytene chromosome structure. Inter se crosses between six strains carrying Top2 missense alleles generated morphologically normal trans-heterozygous adults, which showed delayed development and were female sterile. Complementation occurred between alleles encoding Top2 proteins with amino acid substitutions in the same functional domain and between alleles encoding proteins with substitutions in different functional domains. Two complementing alleles encode proteins with amino acid substitutions associated with drug resistance. These observations suggest that dimerization of mutant Top2 monomers can restore enzymatic function. Our studies establish the first series of Top2 alleles in a multicellular organism. Future analyses of these alleles will enhance our knowledge about the contributions made by type II topoisomerases to development.

A partial flip classroom exercise in a large introductory general biology course increases performance at multiple levels

Abstract Incorporation of active learning into large lecture classes is gaining popularity as a pedagogical method due to its known benefits in helping learning outcomes. A more recent active learning technique that has emerged is the flipped classroom. In this study, we investigated the effects of incorporating a ‘partial-flip’ into an introductory general biology course, where only a portion of the class time was spent in a flipped classroom format. This partial flip presented the classic biology experiment of Meselson and Stahl that discovered the mechanism of DNA replication. Performance on in-class formative assessments and subsequent summative assessments (eg out-of-class assignments and exams relating to this material) was compared between a class that had the partial flip and a control class that had a traditional lecture. The partial flip students scored higher on in-class formative questions, specific exam questions and final exam essay questions. We found that the partial flip had different effects in males versus females depending on the assessment. The partial flip manipulation appeared equally effective in aiding both below and above average students in formative assessments. Overall, this study shows that the partial flip classroom can be an effective technique to incorporate into existing courses and that it does provide some benefits compared to traditional lecture.

Adaptations: Using Darwin's Origin to teach biology and writing

Charles Darwins On the Origin of Species is at once familiar and unfamiliar. Everyone knows that the Origin introduced the world to the idea of evolution by natural selection, but few of us have actually read it. We suggest that it is worth taking the time not only to read what Darwin had to say, but also to use the Origin to teach both biology and writing. It provides scientific lessons in areas beyond evolutionary biology, such as ecology and biogeography. In addition, it provides valuable rhetorical lessons—how to construct an argument, write persuasively, make use of evidence, know your audience, and anticipate counterarguments. We have been using the Origin in various classes for several years, introducing new generations to Darwin, in his own words.