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The correct spatial expression of two Drosophila bithorax complex (BX-C) genes, abdominal-A (abdA) and Abdominal-B (AbdB), is dependent on the 100-kb intergenic infraabdominal (iab) region. The iab region is known to contain a number of different domains (iab2 through iab8) that harbor cis-regulatory elements responsible for directing expression of abdA and AbdB in the second through eighth abdominal segments. Here, we use in situ hybridization to perform high-resolution mapping of the transcriptional activity in the iab control regions. We show that transcription of the control regions themselves is abundant and precedes activation of the abdA and AbdB genes. As with the homeotic genes of the BX-C, the transcription patterns of the RNAs from the iab control regions demonstrate colinearity with the sequence of the iab regions along the chromosome and the domains in the embryo under the control of the specific iab regions. These observations suggest that the intergenic RNAs may play a role in initiating cis regulation at the BX-C early in development.

Edward B.Lewis' science is the bridge linking experimental genetics as conducted in the first half of the twentieth century, and the powerful molecular genetic approaches that revolutionized the field in its last quarter.

The extensive infraabdominal (iab) region contains a number of cis-regulatory elements, including enhancers, silencers, and insulators responsible for directing the developmental expression of the abdominal-A and Abdominal-B homeotic genes at the Drosophila bithorax complex. It is unclear how these regulatory elements are primed for activity early in embryogenesis, but the 100-kb intergenic region is subject to a complex transcriptional program. Here, we use molecular and genetic methods to examine the functional activity of the RNAs produced from this region and their role in cis regulation. We show that a subset of these transcripts demonstrates a distinct pattern of cellular localization. Furthermore, the transcripts from each iab region are discrete and the transcripts do not spread across the insulator elements that delineate the iab regions. In embryos carrying a Mcp deletion, the intergenic transcription pattern is disrupted in the iab4 region and the fourth abdominal segment is transformed into the fifth. We propose that intergenic transcription is required early in embryogenesis to initiate the activation of the Drosophila bithorax complex and define the domains of activity for the iab cis-regulatory elements. We also discuss a possible mechanism by which this may occur.

While Edward B. (‘Ed’) Lewis is famous for his contributions to genetics anddev- opmental biology y, few have read his research papers. One reason for this is availability, man ny having been published in obscure journalsor as book chapters. A second is because his papers in those ?elds are very dif?cult to read. The dif?culty derives from the fact that Lewis has published infrequently, thus manypapers are condensed reviews of man nyyears’ work presented largely in summary form rather than in detail. It is not unusual for the reader to have to infer the experimental methods, even the results, from a few sentences. Furthermore, he often presents his results in terms of abstract models; thus it can be dif?cult to separate the data from the models. Ama ajor goal of this book is to make Lewis’ keypapers accessible to researchers and students. The papers are grouped into several sections that re?ect the changing focus of his research. Each section is preceded by commentary designed to place the papers in historical perspective, with respect to Lewis’ own ideas as well as to those of the larger scienti?c community. The commentaries attempt to highlight the key methods and results—as well as the signi?cance—of each paper by explaining the science in terms that should be understandable to upper-level undergraduates, graduate students and professional researchers.

The sequence of the Drosophila melanogaster genome presented in this issue of Science is the latest milestone in nine decades of research on this organism. Genetic and physical mapping, whole-genome mutational screens, and functional alteration of the genome by gene transfer were pioneered in metazoans with the use of this small fruit fly. Here we look at some of the instances in which work on Drosophila has led to major conceptual or technical breakthroughs in our understanding of animal genomes.

Disproof of this hypothesis required the discovery of the cis-trans position effect in Drosophila and the recovery of both wild-type and double-mutant recombinants from flies heterozygous for the Star and asteroid rough-eye mutations (LEWIS 1942, 1945). For example, the double mutation y^sup 2^ sc was first obtained as a rare male crossover from large-scale mating of y^sup 2^ sc females in which all of the other major chromosomes were structurally heterozygous for chromosomal rearrangements (E. B. LEWIS, unpublished results).

The bithorax complex (BX-C) of Drosophila, one of two complexes that act as master regulators of the body plan of the fly, has now been entirely sequenced and comprises ≈315,000 bp, only 1.4% of which codes for protein. Analysis of this sequence reveals significantly overrepresented DNA motifs of unknown, as well as known, functions in the nonprotein-coding portion of the sequence. The following types of motifs in that portion are analyzed: (i) concatamers of mono-, di-, and trinucleotides; (ii) tightly clustered hexanucleotides (spaced ≤5 bases apart); (iii) direct and reverse repeats longer than 20 bp; and (iv) a number of motifs known from biochemical studies to play a role in the regulation of the BX-C. The hexanucleotide AGATAC is remarkably overrepresented and is surmised to play a role in chromosome pairing. The positions of sites of highly overrepresented motifs are plotted for those that occur at more than five sites in the sequence, when <0.5 case is expected. Expected values are based on a third-order Markov chain, which is the optimal order for representing the BXCALL sequence.

The bithorax complex (BX-C) of Drosophila, one of two complexes that act as master regulators of the body plan of the fly, is included within a sequence of 338,234 bp (SEQ89E). This paper presents the strategy used in sequencing SEQ89E and an analysis of its open reading frames. The BX-C sequence (BXCALL) contains 314,895 bp obtained by deletion of putative genes that are located at each end of SEQ89E and appear to be functionally unrelated to the BX-C. Only 1.4% of BXCALL codes for the three homeodomain-containing proteins of the complex. Principal findings include a putative ABD-A protein (ABD-AII) larger than a previously known ABD-A protein and a putative glucose transporter-like gene (1521 bp) located at or near the bithoraxoid (bxd), infra-abdominal-2 (iab-2) boundary on the opposite strand relative to that of the homeobox-containing genes.

The sequence of the Drosophila melanogaster genome presented in this issue of Science is the latest milestone in nine decades of research on this organism. Genetic and physical mapping, whole-genome mutational screens, and functional alteration of the genome by gene transfer were pioneered in metazoans with the use of this small fruit fly. Here we look at some of the instances in which work on Drosophila has led to major conceptual or technical breakthroughs in our understanding of animal genomes.