CiteULike: dpollard's drosophila

Hitchhiking effects of recurrent beneficial amino acid substitutions in the Drosophila melanogaster genome

Peter Andolfatto — 2007-11-10T18:10:48-00:00

Genome Res. (7 November 2007), gr.6691007.

Several recent studies have estimated that a large fraction of amino acid divergence between species of Drosophila was fixed by positive selection, using statistical approaches based on the McDonald-Kreitman test. However, little is known about associated selection coefficients of beneficial amino acid mutations. Recurrent selective sweeps associated with adaptive substitutions should leave a characteristic signature in genome variability data that contains information about the frequency and strength of selection. Here, I document a significant negative correlation between the level and the frequency of synonymous site polymorphism and the rate of protein evolution in highly recombining regions of the X chromosome of D. melanogaster. This pattern is predicted by recurrent adaptive protein evolution and suggests that adaptation is an important determinant of patterns of neutral variation genome-wide. Using a maximum likelihood approach, I estimate the product of the rate and strength of selection under a recurrent genetic hitchhiking model, [IMG]f1.gif" ALT="Formula" BORDER="0">2Nes [~] 3 x 108. Using an approach based on the McDonald-Kreitman test, I estimate that [~]50% of divergent amino acids were driven to fixation by positive selection, implying that beneficial amino acid substitutions are of weak effect on average, on the order of 105 (i.e., 2Nes [~] 40). Two implications of these results are that most adaptive substitutions will be difficult to detect in genome scans of selection and that population size (and genetic drift) may be an important determinant of the evolutionary dynamics of protein adaptation. 10.1101/gr.6691007

Delimiting the conserved features of hunchback function for the trunk organization of insects.

Henrique Marques-Souza — 2008-02-01T06:04:23-00:00

Development (23 January 2008)

The gap gene hunchback in Drosophila acts during syncytial blastoderm stage via a short-range gradient and concentration-dependent activation or repression of target genes. Orthologues of hunchback can be easily found in other insects, but it has been unclear how well its functions are conserved. The segmentation process in most insect embryos occurs under cellular conditions, which should not allow the formation of diffusion-controlled transcription factor gradients. We have studied here in detail the function of hunchback in the short germ embryo of Tribolium using parental RNAi and interaction with possible target genes. We find that hunchback is a major regulator of the trunk gap genes and Hox genes in Tribolium, but may only indirectly be required to regulate other segmentation genes. The core function of hunchback appears to be the setting of the Ultrabithorax expression border via a repression effect, and the activation of the Krüppel expression domain. These regulatory effects are likely to be direct and are conserved between Drosophila and Tribolium. We find no evidence for a classical gap phenotype in the form of loss of segments in the region of expression of hunchback. However, the phenotypic effects in Tribolium are highly comparable with those found for other short germ embryos, i.e. the core functions of hunchback in Tribolium appear to be the same in these other insects, although they are evolutionarily more distant to Tribolium, than Tribolium is to Drosophila. These results allow the disentanglement of the conserved role of hunchback in insects from the derived features that have been acquired in the lineage towards Drosophila. Given that the gap phenotype appears to occur only in long germ embryos and that the main role of hunchback appears to be the regionalization of the embryo, it may be appropriate to revive an alternative name for the class of gap genes, namely 'cardinal genes'.

Inferring genome-scale rearrangement phylogeny and ancestral gene order: A Drosophila case study

Arjun Bhutkar — 2007-11-09T08:38:41-00:00

Genome Biology, Vol. 8 (08 November 2007), R236.

Contrasting the Efficacy of Selection on the X and Autosomes in Drosophila.

Nadia D Singh — 2008-01-11T18:02:01-00:00

Mol Biol Evol (13 December 2007)

To investigate the relative efficacy of both positive and purifying natural selection on the X chromosome and the autosomes in Drosophila, we compared rates and patterns of molecular evolution between these chromosome sets using the newly available alignments of orthologous genes from twelve species. Parameters that may influence the relative X vs. autosomal substitution rates include the relative effective population sizes, the male and female germline mutation rates, the distribution of allelic effects on fitness, and the degree of dominance of novel mutations. Our analysis reveals that codon usage bias is consistently greater for X-linked genes, suggesting that purifying selection consistently has greater efficacy on the X chromosome than on the autosomes across the Drosophila phylogeny. However, our results are less consistent with respect to the efficacy of positive selection, with only some lineages showing a higher substitution rate on the X chromosome. This suggests that either the distribution of selective effects of mutations or other relevant parameters are sufficiently variable across species to tip the balance in different ways in individual lineages. These data suggest that rates of substitution are not solely governed by adaptive evolution. This genome-wide analysis provides a clear picture that the efficacy of selection varies intragenomically, and that this effect is markedly more consistent across the phylogeny in the case of purifying selection. Our results also suggest that simple models that predict systematic differences in rates of evolution between the X and the autosomes can only be made to be compatible with these Drosophila data if the relevant population genetic parameters that drive substitution rates differ among species and chromosomal contexts.

Evolutionary changes in cis and trans gene regulation

Patricia Wittkopp — 2006-01-16T14:21:31-00:00

Nature, Vol. 430, No. 6995. (1 July 2004), pp. 85-88.

Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila.

N Gompel — 2006-01-18T01:41:02-00:00

Nature, Vol. 433, No. 7025. (3 February 2005), pp. 481-487.

The gain, loss or modification of morphological traits is generally associated with changes in gene regulation during development. However, the molecular bases underlying these evolutionary changes have remained elusive. Here we identify one of the molecular mechanisms that contributes to the evolutionary gain of a male-specific wing pigmentation spot in Drosophila biarmipes, a species closely related to Drosophila melanogaster. We show that the evolution of this spot involved modifications of an ancestral cis-regulatory element of the yellow pigmentation gene. This element has gained multiple binding sites for transcription factors that are deeply conserved components of the regulatory landscape controlling wing development, including the selector protein Engrailed. The evolutionary stability of components of regulatory landscapes, which can be co-opted by chance mutations in cis-regulatory elements, might explain the repeated evolution of similar morphological patterns, such as wing pigmentation patterns in flies.

Genome-wide analysis of clustered Dorsal binding sites identifies putative target genes in the Drosophila embryo.

M Markstein — 2007-12-05T12:38:16-00:00

Proc Natl Acad Sci U S A, Vol. 99, No. 2. (22 January 2002), pp. 763-768.

Metazoan genomes contain vast tracts of cis-regulatory DNA that have been identified typically through tedious functional assays. As a result, it has not been possible to uncover a cis-regulatory code that links primary DNA sequences to gene expression patterns. In an initial effort to determine whether coordinately regulated genes share a common "grammar," we have examined the distribution of Dorsal recognition sequences in the Drosophila genome. Dorsal is one of the best-characterized sequence-specific transcription factors in Drosophila. The homeobox gene zerknullt (zen) is repressed directly by Dorsal, and this repression is mediated by a 600-bp silencer, the ventral repression element (VRE), which contains four optimal Dorsal binding sites. The arrangement and sequence of the Dorsal recognition sequences in the VRE were used to develop a computational algorithm to search the Drosophila genome for clusters of optimal Dorsal binding sites. There are 15 regions in the genome that contain three or more optimal sites within a span of 400 bp or less. Three of these regions are associated with known Dorsal target genes: sog, zen, and Brinker. The Dorsal binding cluster in sog is shown to mediate lateral stripes of gene expression in response to low levels of the Dorsal gradient. Two of the remaining 12 clusters are shown to be associated with genes that exhibit asymmetric patterns of expression across the dorsoventral axis. These results suggest that bioinformatics can be used to identify novel target genes and associated regulatory DNAs in a gene network.

Transcriptional regulation of a pair-rule stripe in Drosophila.

S Small — 2007-12-05T19:30:34-00:00

Genes Dev, Vol. 5, No. 5. (May 1991), pp. 827-839.

The periodic, seven-stripe pattern of the primary pair-rule gene even-skipped (eve) is initiated by crude, overlapping gradients of maternal and gap gene proteins in the early Drosophila embryo. Previous genetic studies suggest that one of the stripes, stripe 2, is initiated by the maternal morphogen bicoid (bcd) and the gap protein hunchback (hb), while the borders of the stripe are formed by selective repression, involving the gap protein giant (gt) in anterior regions and the Krüppel (Kr) protein in posterior regions. Here, we present several lines of evidence that are consistent with this model for stripe 2 expression, including in vitro DNA-binding experiments and transient cotransfection assays in cultured cells. These experiments suggest that repression involves a competition or short-range quenching mechanism, whereby the binding of gt and Kr interferes with the binding or activity of bcd and hb activators at overlapping or neighboring sites within the eve stripe 2 promoter element. Such short-range repression could reflect a general property of promoters composed of multiple, but autonomous regulatory elements.

Accurate gene-tree reconstruction by learning gene- and species-specific substitution rates across multiple complete genomes

Matthew Rasmussen — 2007-11-12T17:38:22-00:00

Genome Res. (7 November 2007), gr.7105007.

Comparative genomics provides a general methodology for discovering functional DNA elements and understanding their evolution. The availability of many related genomes enables more powerful analyses, but requires rigorous phylogenetic methods to resolve orthologous genes and regions. Here, we use 12 recently sequenced Drosophila genomes and nine fungal genomes to address the problem of accurate gene-tree reconstruction across many complete genomes. We show that existing phylogenetic methods that treat each gene tree in isolation show large-scale inaccuracies, largely due to insufficient phylogenetic information in individual genes. However, we find that gene trees exhibit common properties that can be exploited for evolutionary studies and accurate phylogenetic reconstruction. Evolutionary rates can be decoupled into gene-specific and species-specific components, which can be learned across complete genomes. We develop a phylogenetic reconstruction methodology that exploits these properties and achieves significantly higher accuracy, addressing the species-level heterotachy and enabling studies of gene evolution in the context of species evolution. 10.1101/gr.7105007

Dynamics and function of intron sequences of the wingless gene during the evolution of the Drosophila genus.

J Costas — 2007-11-21T01:23:08-00:00

Evol Dev, Vol. 6, No. 5. (t 2004), pp. 325-335.

To understand the function and evolution of genes with complex patterns of expression, such as the Drosophila wingless gene, it is essential to know how their transcription is regulated. However, extracting the relevant regulatory information from a genome is still a complex task. We used a combination of comparative genomics and functional approaches to identify putative regulatory sequences in two introns (1 and 3) of the wingless gene and to infer their evolution. Comparison of the sequences obtained from several Drosophila species revealed colinear and well-conserved sequence blocks in both introns. Drosophila willistoni showed a rate of evolution, in both introns, faster than expected from its phylogenetic position. Intron 3 appeared to be composed of two separate modules, one of them lost in the willistoni group. We tested whether sequence conservation in noncoding regions is a reliable indicator of regulatory function and, if this function is conserved, by analyzing D. melanogaster transgenic reporter lines harboring intron 3 sequences from D. melanogaster (Sophophora subgenus) and the species from the Drosophila subgenus presenting the most divergent sequence, D. americana. The analysis indicated that intron 3 contains pupal enhancers conserved during the evolution of the genus, despite the fact that only 30% of the D. melanogaster intron 3 sequences lie in conserved blocks. Additional analysis of D. melanogaster transgenic reporter lines harboring intron 3 sequences from D. willistoni revealed the absence of an abdomen-specific expression pattern, probably due to the above-mentioned loss of a regulatory module in this species.

Turnover of binding sites for transcription factors involved in early Drosophila development.

J Costas — 2007-10-16T21:11:16-00:00

Gene, Vol. 310 (22 May 2003), pp. 215-220.

Despite the importance of cis-regulatory regions in evolution, little is know about their evolutionary dynamics. In this report, we analyze the process of evolution of binding sites for transcription factors using as a model a well characterized system, the Drosophila early developmental enhancers. We compare the sequences of eight enhancer regions for early developmental genes between Drosophila melanogaster and other two species, Drosophila virilis and Drosophila pseudoobscura, searching for the presence/absence of 104 biochemically verified binding sites from D. melanogaster. We also modeled the binding specificity of each binding site by the use of well-defined positional weight matrices (PWMs). The comparisons showed that turnover of binding sites seems to fit a molecular clock, at an approximate rate of 0.94% of gain/loss of binding sites per million years. This intense turnover affects both high and low affinity binding sites at the same extent. Furthermore, the subset of overlapping binding sites is also subjected to this high turnover. Conserved binding sites seem to be constrained to maintain not only location but also the exact sequence at each particular position. Finally, we detected a significant decrease in mean PWM scores for the D. virilis binding sites in the case of Hunchback. Possible explanations for this fact are discussed.

Unmasking Activation of the Zygotic Genome Using Chromosomal Deletions in the Drosophila Embryo

Stefano De Renzis — 2007-08-22T19:11:28-00:00

PLoS Biology, Vol. 5, No. 5. (1 May 2007), e117.

During the maternal-to-zygotic transition, a developing embryo integrates post-transcriptional regulation of maternal mRNAs with transcriptional activation of its own genome. By combining chromosomal ablation in Drosophila with microarray analysis, we characterized the basis of this integration. We show that the expression profile for at least one third of zygotically active genes is coupled to the concomitant degradation of the corresponding maternal mRNAs. The embryo uses transcription and degradation to generate localized patterns of expression, and zygotic transcription to degrade distinct classes of maternal transcripts. Although degradation does not appear to involve a simple regulatory code, the activation of the zygotic genome starts from intronless genes sharing a common cis-element. This cis-element interacts with a single protein, the Bicoid stability factor, and acts as a potent enhancer capable of timing the activity of an exogenous transactivator. We propose that this regulatory mode links morphogen gradients with temporal regulation during the maternal-to-zygotic transition.

Global analysis of patterns of gene expression during Drosophila embryogenesis

Pavel Tomancak — 2007-07-25T03:21:47-00:00

Genome Biology, Vol. 8 (23 July 2007), R145.

Reliable prediction of regulator targets using 12 Drosophila genomes.

Alexander Stark — 2007-11-16T23:59:59-00:00

Genome Res (7 November 2007)

Gene expression is regulated pre- and post-transcriptionally via cis-regulatory DNA and RNA motifs. Identification of individual functional instances of such motifs in genome sequences is a major goal for inferring regulatory networks yet has been hampered due to the motifs' short lengths that lead to many chance matches and poor signal-to-noise ratios. In this paper, we develop a general methodology for the comparative identification of functional motif instances across many related species, using a phylogenetic framework that accounts for the evolutionary relationships between species, allows for motif movements, and is robust against missing data due to artifacts in sequencing, assembly, or alignment. We also provide a robust statistical framework for evaluating motif confidence, which enables us to translate evolutionary conservation into a confidence measure for each motif instance, correcting for varying motif length, composition, and background conservation of the target regions. We predict targets of fly transcription factors and miRNAs in alignments of 12 recently sequenced Drosophila species. When compared to extensive genome-wide experimental data, predicted targets are of high quality, matching and surpassing ChIP-chip microarrays and recovering miRNA targets with high sensitivity. The resulting regulatory network suggests significant redundancy between pre- and post-transcriptional regulation of gene expression.

Constraint and turnover in sex-biased gene expression in the genus Drosophila

Yu Zhang — 2007-11-07T18:45:14-00:00

Nature, Vol. 450, No. 7167., pp. 233-237.

The regulatory content of intergenic DNA shapes genome architecture.

CE Nelson — 2006-07-20T14:14:26-00:00

Genome Biol, Vol. 5, No. 4. (2004)

BACKGROUND: Factors affecting the organization and spacing of functionally unrelated genes in metazoan genomes are not well understood. Because of the vast size of a typical metazoan genome compared to known regulatory and protein-coding regions, functional DNA is generally considered to have a negligible impact on gene spacing and genome organization. In particular, it has been impossible to estimate the global impact, if any, of regulatory elements on genome architecture. RESULTS: To investigate this, we examined the relationship between regulatory complexity and gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity, such that the amount of noncoding DNA between a gene and its nearest neighbors correlates positively with that gene's regulatory complexity. Genes with complex functions are flanked by significantly more noncoding DNA than genes with simple or housekeeping functions. Genes of low regulatory complexity are associated with approximately the same amount of noncoding DNA in D. melanogaster and C. elegans, while loci of high regulatory complexity are significantly larger in the more complex animal. Complex genes in C. elegans have larger 5' than 3' noncoding intervals, whereas those in D. melanogaster have roughly equivalent 5' and 3' noncoding intervals. CONCLUSIONS: Intergenic distance, and hence genome architecture, is highly nonrandom. Rather, it is shaped by regulatory information contained in noncoding DNA. Our findings suggest that in compact genomes, the species-specific loss of nonfunctional DNA reveals a landscape of regulatory information by leaving a profile of functional DNA in its wake.

Large-Scale Discovery of Promoter Motifs in Drosophila melanogaster

Thomas Down — 2007-01-23T14:07:06-00:00

PLoS Computational Biology, Vol. 3, No. 1. (1 January 2007), e7.

A key step in understanding gene regulation is to identify the repertoire of transcription factor binding motifs (TFBMs) that form the building blocks of promoters and other regulatory elements. Identifying these experimentally is very laborious, and the number of TFBMs discovered remains relatively small, especially when compared with the hundreds of transcription factor genes predicted in metazoan genomes. We have used a recently developed statistical motif discovery approach, NestedMICA, to detect candidate TFBMs from a large set of Drosophila melanogaster promoter regions. Of the 120 motifs inferred in our initial analysis, 25 were statistically significant matches to previously reported motifs, while 87 appeared to be novel. Analysis of sequence conservation and motif positioning suggested that the great majority of these discovered motifs are predictive of functional elements in the genome. Many motifs showed associations with specific patterns of gene expression in the D. melanogaster embryo, and we were able to obtain confident annotation of expression patterns for 25 of our motifs, including eight of the novel motifs. The motifs are available through Tiffin, a new database of DNA sequence motifs. We have discovered many new motifs that are overrepresented in D. melanogaster promoter regions, and offer several independent lines of evidence that these are novel TFBMs. Our motif dictionary provides a solid foundation for further investigation of regulatory elements in Drosophila, and demonstrates techniques that should be applicable in other species. We suggest that further improvements in computational motif discovery should narrow the gap between the set of known motifs and the total number of transcription factors in metazoan genomes.

Principles of Genome Evolution in the Drosophila melanogaster Species Group

José Ranz — 2007-06-14T01:02:58-00:00

PLoS Biology, Vol. 5, No. 6. (1 June 2007), e152.

That closely related species often differ by chromosomal inversions was discovered by Sturtevant and Plunkett in 1926. Our knowledge of how these inversions originate is still very limited, although a prevailing view is that they are facilitated by ectopic recombination events between inverted repetitive sequences. The availability of genome sequences of related species now allows us to study in detail the mechanisms that generate interspecific inversions. We have analyzed the breakpoint regions of the 29 inversions that differentiate the chromosomes of Drosophila melanogaster and two closely related species, D. simulans and D. yakuba, and reconstructed the molecular events that underlie their origin. Experimental and computational analysis revealed that the breakpoint regions of 59% of the inversions (17/29) are associated with inverted duplications of genes or other nonrepetitive sequences. In only two cases do we find evidence for inverted repetitive sequences in inversion breakpoints. We propose that the presence of inverted duplications associated with inversion breakpoint regions is the result of staggered breaks, either isochromatid or chromatid, and that this, rather than ectopic exchange between inverted repetitive sequences, is the prevalent mechanism for the generation of inversions in the melanogaster species group. Outgroup analysis also revealed evidence for widespread breakpoint recycling. Lastly, we have found that expression domains in D. melanogaster may be disrupted in D. yakuba, bringing into question their potential adaptive significance.

Purifying Selection Maintains Highly Conserved Noncoding Sequences in Drosophila.

Sònia Casillas — 2007-07-26T13:46:14-00:00

Mol Biol Evol (23 July 2007)

The majority of metazoan genomes consist of non-protein coding regions, however the functional significance of most noncoding DNA sequences remains unknown. Highly conserved noncoding sequences (CNSs) have proven to be reliable indicators of functionally constrained sequences such as cis-regulatory elements and noncoding RNA genes. However, CNSs may arise from non-selective evolutionary processes such as genomic regions with extremely low mutation rates known as mutation "cold spots." Here we combine comparative genomic data from recently completed insect genome projects with population genetic data in D. melanogaster, to test predictions of the mutational cold spot model of CNS evolution in the genus Drosophila. We find that point mutations in intronic and intergenic CNSs exhibit a significant reduction in levels of divergence relative to levels of polymorphism, as well as a significant excess of rare derived alleles, compared with either the non-conserved spacer regions between CNSs or with four-fold silent sites in coding regions. Controlling for the effects of purifying selection, we find no evidence of positive selection acting on Drosophila CNSs, although we do find evidence for the action of recurrent positive selection in the spacer regions between CNSs. We estimate that approximately 85% of sites in Drosophila CNSs are under constraint with selection coefficients (N(e)S) on the order of 10-100, and thus the estimated strength and number of sites under purifying selection is greater for Drosophila CNSs relative to those in the human genome, These patterns of non-neutral molecular evolution are incompatible with the mutational cold spot hypothesis to explain the existence of CNSs in Drosophila and, coupled with similar findings in mammals, argue against the general likelihood that CNSs are generated by mutational cold spots in any metazoan genome.

Rapid sequence turnover at an intergenic locus in Drosophila.

ND Singh — 2007-11-14T21:13:05-00:00

Mol Biol Evol, Vol. 21, No. 4. (April 2004), pp. 670-680.

Closely related species of Drosophila tend to have similar genome sizes. The strong imbalance in favor of small deletions relative to insertions implies that the unconstrained DNA in Drosophila is unlikely to be passively inherited from even closely related ancestors, and yet most DNA in Drosophila genomes is intergenic and potentially unconstrained. In an attempt to investigate the maintenance of this intergenic DNA, we studied the evolution of an intergenic locus on the fourth chromosome of the Drosophila melanogaster genome. This 1.2-kb locus is marked by two distinct, large insertion events: a nuclear transposition of a mitochondrial sequence and a transposition of a nonautonomous DNA transposon DNAREP1_DM. Because we could trace the evolutionary histories of these sequences, we were able to reconstruct the length evolution of this region in some detail. We sequenced this locus in all four species of the D. melanogaster species complex: D. melanogaster, D. simulans, D. sechellia, and D. mauritiana. Although this locus is similar in size in these four species, less than 10% of the sequence from the most recent common ancestor remains in D. melanogaster and all of its sister species. This region appears to have increased in size through several distinct insertions in the ancestor of the D. melanogaster species complex and has been shrinking since the split of these lineages. In addition, we found no evidence suggesting that the size of this locus has been maintained over evolutionary time; these results are consistent with the model of a dynamic equilibrium between persistent DNA loss through small deletions and more sporadic DNA gain through less frequent but longer insertions. The apparent stability of genome size in Drosophila may belie very rapid sequence turnover at intergenic loci.

Pseudogene evolution in Drosophila suggests a high rate of DNA loss.

DA Petrov — 2007-11-14T21:12:26-00:00

Mol Biol Evol, Vol. 15, No. 11. (November 1998), pp. 1562-1567.

How intron splicing affects the deletion and insertion profile in Drosophila melanogaster.

SE Ptak — 2007-11-14T21:11:28-00:00

Genetics, Vol. 162, No. 3. (November 2002), pp. 1233-1244.

Studies of "dead-on-arrival" transposable elements in Drosophila melanogaster found that deletions outnumber insertions approximately 8:1 with a median size for deletions of approximately 10 bp. These results are consistent with the deletion and insertion profiles found in most other Drosophila pseudogenes. In contrast, a recent study of D. melanogaster introns found a deletion/insertion ratio of 1.35:1, with 84% of deletions being shorter than 10 bp. This discrepancy could be explained if deletions, especially long deletions, are more frequently strongly deleterious than insertions and are eliminated disproportionately from intron sequences. To test this possibility, we use analysis and simulations to examine how deletions and insertions of different lengths affect different components of splicing and determine the distribution of deletions and insertions that preserve the original exons. We find that, consistent with our predictions, longer deletions affect splicing at a much higher rate compared to insertions and short deletions. We also explore other potential constraints in introns and show that most of these also disproportionately affect large deletions. Altogether we demonstrate that constraints in introns may explain much of the difference in the pattern of deletions and insertions observed in Drosophila introns and pseudogenes.

DNA loss and evolution of genome size in Drosophila.

DA Petrov — 2007-09-10T12:32:15-00:00

Genetica, Vol. 115, No. 1. (May 2002), pp. 81-91.

Mutation is often said to be random. Although it must be true that mutation is ignorant about the adaptive needs of the organism and thus is random relative to them as a rule, mutation is not truly random in other respects. Nucleotide substitutions, deletions, insertions, inversions, duplications and other types of mutation occur at different rates and are effected by different mechanisms. Moreover the rates of different mutations vary from organism to organism. Differences in mutational biases, along with natural selection, could impact gene and genome evolution in important ways. For instance, several recent studies have suggested that differences in insertion/deletion biases lead to profound differences in the rate of DNA loss in animals and that this difference per se can lead to significant changes in genome size. In particular, Drosophila melanogaster appears to have a very high rate of deletions and the correspondingly high rate of DNA loss and a very compact genome. To assess the validity of these studies we must first assess the validity of the measurements of indel biases themselves. Here I demonstrate the robustness of indel bias measurements in Drosophila, by comparing indel patterns in different types of nonfunctional sequences. The indel pattern and the high rate of DNA loss appears to be shared by all known nonfunctional sequences, both euchromatic and heterochromatic, transposable and non-transposable, repetitive and unique. Unfortunately all available nonfunctional sequences are untranscribed and thus effects of transcription on indel bias cannot be assessed. I also discuss in detail why it is unlikely that natural selection for or against DNA loss significantly affects current estimates of indel biases.

Pseudogene evolution and natural selection for a compact genome.

DA Petrov — 2007-11-14T20:59:40-00:00

J Hered, Vol. 91, No. 3. (n 2000), pp. 221-227.

Pseudogenes are nonfunctional copies of protein-coding genes that are presumed to evolve without selective constraints on their coding function. They are of considerable utility in evolutionary genetics because, in the absence of selection, different types of mutations in pseudogenes should have equal probabilities of fixation. This theoretical inference justifies the estimation of patterns of spontaneous mutation from the analysis of patterns of substitutions in pseudogenes. Although it is possible to test whether pseudogene sequences evolve without constraints for their protein-coding function, it is much more difficult to ascertain whether pseudogenes may affect fitness in ways unrelated to their nucleotide sequence. Consider the possibility that a pseudogene affects fitness merely by increasing genome size. If a larger genome is deleterious--for example, because of increased energetic costs associated with genome replication and maintenance--then deletions, which decrease the length of a pseudogene, should be selectively advantageous relative to insertions or nucleotide substitutions. In this article we examine the implications of selection for genome size relative to small (1-400 bp) deletions, in light of empirical evidence pertaining to the size distribution of deletions observed in Drosophila and mammalian pseudogenes. There is a large difference in the deletion spectra between these organisms. We argue that this difference cannot easily be attributed to selection for overall genome size, since the magnitude of selection is unlikely to be strong enough to significantly affect the probability of fixation of small deletions in Drosophila.

Evidence for DNA loss as a determinant of genome size.

DA Petrov — 2006-06-11T03:58:52-00:00

Science, Vol. 287, No. 5455. (11 February 2000), pp. 1060-1062.

Eukaryotic genome sizes range over five orders of magnitude. This variation cannot be explained by differences in organismic complexity (the C value paradox). To test the hypothesis that some variation in genome size can be attributed to differences in the patterns of insertion and deletion (indel) mutations among organisms, this study examines the indel spectrum in Laupala crickets, which have a genome size 11 times larger than that of Drosophila. Consistent with the hypothesis, DNA loss is more than 40 times slower in Laupala than in Drosophila.

High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups.

DA Petrov — 2007-11-14T20:58:05-00:00

Mol Biol Evol, Vol. 15, No. 3. (March 1998), pp. 293-302.

We recently proposed that patterns of evolution of non-LTR retrotransposable elements can be used to study patterns of spontaneous mutation. Transposition of non-LTR retrotransposable elements commonly results in creation of 5' truncated, "dead-on-arrival" copies. These inactive copies are effectively pseudogenes and, according to the neutral theory, their molecular evolution ought to reflect rates and patterns of spontaneous mutation. Maximum parsimony can be used to separate the evolution of active lineages of a non-LTR element from the fate of the "dead-on-arrival" insertions and to directly assess the relative frequencies of different types of spontaneous mutations. We applied this approach using a non-LTR element, Helena, in the Drosophila virilis group and have demonstrated a surprisingly high incidence of large deletions and the virtual absence of insertions. Based on these results, we suggested that Drosophila in general may exhibit a high rate of spontaneous large deletions and have hypothesized that such a high rate of DNA loss may help to explain the puzzling dearth of bona fide pseudogenes in Drosophila. We also speculated that variation in the rate of spontaneous deletion may contribute to the divergence of genome size in different taxa by affecting the amount of superfluous "junk" DNA such as, for example, pseudogenes or long introns. In this paper, we extend our analysis to the D. melanogaster subgroup, which last shared a common ancestor with the D. virilis group approximately 40 MYA. In a different region of the same transposable element, Helena, we demonstrate that inactive copies accumulate deletions in species of the D. melanogaster subgroup at a rate very similar to that of the D. virilis group. These results strongly suggest that the high rate of DNA loss is a general feature of Drosophila and not a peculiar property of a particular stretch of DNA in a particular species group.

Trash DNA is what gets thrown away: high rate of DNA loss in Drosophila.

DA Petrov — 2007-11-14T20:55:42-00:00

Gene, Vol. 205, No. 1-2. (31 December 1997), pp. 279-289.

We have recently described a novel method of estimating neutral rates and patterns of spontaneous mutation (Petrov et al., 1996). This method takes advantage of the propensity of non-LTR retrotransposable elements to create non-functional, 'dead-on-arrival' copies as a product of transposition. Maximum parsimony analysis is used to separate the evolution of actively transposing lineages of a non-LTR element from the fate of individual inactive insertions, and thereby allows one to assess directly the relative rates of different types of mutation, including point substitutions, deletions and insertions. Because non-LTR elements enjoy wide phylogenetic distribution, this method can be used in taxa that do not harbor a significant number of bona fide pseudogenes, as is the case in Drosophila (Jeffs and Ashburner, 1991; Weiner et al., 1986). We used this method with Helena, a non-LTR retrotransposable element present in the Drosophila virilis species group. A striking finding was the virtual absence of insertions and remarkably high incidence of large deletions, which combine to produce a high overall rate of DNA loss. On average, the rate of DNA loss in D. virilis is approximately 75 times faster than that estimated for mammalian pseudogenes (Petrov et al., 1996). The high rate of DNA loss should lead to rapid elimination of non-essential DNA and thus may explain the seemingly paradoxical dearth of pseudogenes in Drosophila. Varying rates of DNA loss may also contribute to differences in genome size (Graur et al., 1989; Petrov et al., 1996), thus explaining the celebrated 'C-value' paradox (John and Miklos, 1988). In this paper we outline the theoretical basis of our method, examine the data from this perspective, and discuss potential problems that may bias our estimates.

High intrinsic rate of DNA loss in Drosophila.

DA Petrov — 2007-09-10T12:34:36-00:00

Nature, Vol. 384, No. 6607. (28 November 1996), pp. 346-349.

Pseudogenes are common in mammals but virtually absent in Drosophila. All putative Drosophila pseudogenes show patterns of molecular evolution that are inconsistent with the lack of functional constraints. The absence of bona fide pseudogenes is not only puzzling, it also hampers attempts to estimate rates and patterns of neutral DNA change. The estimation problem is especially acute in the case of deletions and insertions, which are likely to have large effects when they occur in functional genes and are therefore subject to strong purifying selection. We propose a solution to this problem by taking advantage of the propensity of retrotransposable elements without long terminal repeats (non-LTR) to create non-functional, 'dead-on-arrival' copies of themselves as a common by-product of their transpositional cycle. Phylogenetic analysis of a non-LTR element, Helena, demonstrates that copies lose DNA at an unusually high rate, suggesting that lack of pseudogenes in Drosophila is the product of rampant deletion of DNA in unconstrained regions. This finding has important implications for the study of genome evolution in general and the 'C-value paradox' in particular.

Similar Levels of X-linked and Autosomal Nucleotide Variation in African and non-African populations of Drosophila melanogaster

Nadia Singh — 2007-10-26T20:30:51-00:00

BMC Evolutionary Biology, Vol. 7 (25 October 2007), 202.

A logical analysis of the Drosophila gap-gene system.

L Sánchez — 2005-12-08T21:33:25-00:00

J Theor Biol, Vol. 211, No. 2. (21 July 2001), pp. 115-141.

This manuscript focuses on the formal analysis of the gap-gene network involved in Drosophila segmentation. The gap genes are expressed in defined domains along the anterior-posterior axis of the embryo, as a response to asymmetric maternal information in the oocyte. Though many of the individual interactions among maternal and gap genes are reasonably well understood, we still lack a thorough understanding of the dynamic behavior of the system as a whole. Based on a generalized logical formalization, the present analysis leads to the delineation of: (1) the minimal number of distinct, qualitative, functional levels associated with each of the key regulatory factors (the three maternal Bcd, Hb and Cad products, and the four gap Gt, Hb, Kr and Kni products); (2) the most crucial interactions and regulatory circuits of the earliest stages of the segmentation process; (3) the ordering of different regulatory interactions governed by each of these products according to corresponding concentration scales; and (4) the role of gap-gene cross-interactions in the transformation of graded maternal information into discrete gap-gene expression domains. The proposed model allows not only the qualitative reproduction of the patterns of gene expression characterized experimentally, but also the simulation and prediction of single and multiple mutant phenotypes.

From gradients to stripes in Drosophila embryogenesis: filling in the gaps

Rolando Rivera-Pomar — 2007-11-05T21:20:24-00:00

Trends in Genetics, Vol. 12, No. 11. (November 1996), pp. 478-483.

Pattern formation along the anterior-posterior axis of the Drosophila embryo is organized by asymmetrically distributed maternal transcription factors. They initiate a cascade of spatially restricted and interacting zygotic gene activities that provide a molecular blueprint of the larval body at blasioderm stage. The key players in the pattern forming process have been identified. Recent progress has begun to reveal the mechanisms by which coherent positional information of maternal origin becomes transferred into serially repeated zygotic gene expression domains reflecting the metameric body plan of the larva.

Gradients and thresholds: BMP response gradients unveiled in Drosophila embryos

Laurel Raftery — 2007-11-05T21:18:59-00:00

Trends in Genetics, Vol. 19, No. 12. (December 2003), pp. 701-708.

Bone morphogenetic proteins (BMP) direct dorsal-ventral patterning in both invertebrate and vertebrate embryos, with strong evolutionary conservation of molecular components of the pathway. Dorsal-ventral patterning of the early Drosophila embryo is a powerful experimental system to probe mechanisms of BMP gradient formation and interpretation. Recent studies have found that spatial patterns of activated BMP signal transducers in Drosophila go through an unexpected transition: a shallow gradient of weak responses at mid-cellularization changes to a step gradient of stronger responses in cellularized embryos. The transition between two gradients of different shape yields new insights into the progression of Drosophila dorsal-ventral patterning and raises new issues about the mechanisms of gradient formation.

Distance preferences in the arrangement of binding motifs and hierarchical levels in organization of transcription regulatory information.

VJ Makeev — 2006-04-27T19:16:12-00:00

Nucleic Acids Res, Vol. 31, No. 20. (15 October 2003), pp. 6016-6026.

We explored distance preferences in the arrangement of binding motifs for five transcription factors (Bicoid, Krüppel, Hunchback, Knirps and Caudal) in a large set of Drosophila cis-regulatory modules (CRMs). Analysis of non-overlapping binding motifs revealed the presence of periodic signals specific to particular combinations of binding motifs. The most striking periodic signals (10 bp for Bicoid and 11 bp for Hunchback) suggest preferential positioning of some binding site combinations on the same side of the DNA helix. We also analyzed distance preferences in arrangements of highly correlated overlapping binding motifs, such as Bicoid and Krüppel. Based on the distance analysis, we extracted preferential binding site arrangements and proposed models for potential composite elements (CEs) and antagonistic motif pairs involved in the function of developmental CRMs. Our results suggest that there are distinct hierarchical levels in the organization of transcription regulatory information. We discuss the role of the hierarchy in understanding transcriptional regulation and in detection of transcription regulatory regions in genomes.

Making connections: boundaries and insulators in Drosophila.

Robert K Maeda — 2007-10-25T01:14:46-00:00

Curr Opin Genet Dev (26 September 2007)

In eukaryotes, enhancers must often exert their effect over many tens of kilobases of DNA with a choice between many different promoters. Given this situation, elements known as chromatin boundaries have evolved to prevent adventitious interactions between enhancers and promoters. The amenability of Drosophila to molecular genetics has been crucial to the discovery and analysis of these elements. Since these elements are involved in such diverse processes and show little or no sequence similarity between them, no single molecular mechanism has been identified that accounts for their activity. However, over the past approximately 5 years, evidence has accumulated suggesting that boundaries probably function through the formation of long-distance chromatin loops. These loops have been proposed to play a crucial role in both controlling enhancer-promoter interactions and packing DNA.

Temporal ChIP-on-chip reveals Biniou as a universal regulator of the visceral muscle transcriptional network.

JS Jakobsen — 2007-10-04T22:30:54-00:00

Genes Dev, Vol. 21, No. 19. (1 October 2007), pp. 2448-2460.

Smooth muscle plays a prominent role in many fundamental processes and diseases, yet our understanding of the transcriptional network regulating its development is very limited. The FoxF transcription factors are essential for visceral smooth muscle development in diverse species, although their direct regulatory role remains elusive. We present a transcriptional map of Biniou (a FoxF transcription factor) and Bagpipe (an Nkx factor) activity, as a first step to deciphering the developmental program regulating Drosophila visceral muscle development. A time course of chromatin immunoprecipitatation followed by microarray analysis (ChIP-on-chip) experiments and expression profiling of mutant embryos reveal a dynamic map of in vivo bound enhancers and direct target genes. While Biniou is broadly expressed, it regulates enhancers driving temporally and spatially restricted expression. In vivo reporter assays indicate that the timing of Biniou binding is a key trigger for the time span of enhancer activity. Although bagpipe and biniou mutants phenocopy each other, their regulatory potential is quite different. This network architecture was not apparent from genetic studies, and highlights Biniou as a universal regulator in all visceral muscle, regardless of its developmental origin or subsequent function. The regulatory connection of a number of Biniou target genes is conserved in mice, suggesting an ancient wiring of this developmental program.

We gather together: insulators and genome organization.

Julie A Wallace — 2007-10-25T00:59:47-00:00

Curr Opin Genet Dev (1 October 2007)

When placed between an enhancer and promoter, certain DNA sequence elements inhibit enhancer-stimulated gene expression. The best characterized of these enhancer-blocking insulators, gypsy in Drosophila and the CTCF-binding element in vertebrates and flies, stabilize contacts between distant genomic regulatory sites leading to the formation of loop domains. Current results show that CTCF mediates long-range contacts in the mouse beta-globin locus and at the Igf2/H19-imprinted locus. Recently described active chromatin hubs and transcription factories also involve long-range interactions; it is likely that CTCF interferes with their formation when acting as an insulator. The properties of CTCF, and its newly described genomic distribution, suggest that it may play an important role in large-scale nuclear architecture, perhaps mediated by the co-factors with which it interacts in vivo.

Comparing active and repressed expression states of genes controlled by the Polycomb/Trithorax group proteins.

C Beisel — 2007-10-25T00:51:48-00:00

Proc Natl Acad Sci U S A, Vol. 104, No. 42. (16 October 2007), pp. 16615-16620.

Drosophila Polycomb group (PcG) and Trithorax group (TrxG) proteins are responsible for the maintenance of stable transcription patterns of many developmental regulators, such as the homeotic genes. We have used ChIP-on-chip to compare the distribution of several PcG/TrxG proteins, as well as histone modifications in active and repressed genes across the two homeotic complexes ANT-C and BX-C. Our data indicate the colocalization of the Polycomb repressive complex 1 (PRC1) with Trx and the DNA binding protein Pleiohomeotic (Pho) at discrete sequence elements as well as significant chromatin assembly differences in active and inactive regions. Trx binds to the promoters of active genes and noncoding transcripts. Most strikingly, in the active state, Pho covers extended chromatin domains over many kilobases. This feature of Pho, observed on many polytene chromosome puffs, reflects a previously undescribed function. At the hsp70 gene, we demonstrate in mutants that Pho is required for transcriptional recovery after heat shock. Besides its presumptive function in recruiting PcG complexes to their site of action, our results now uncover that Pho plays an additional role in the repression of already induced genes.

CAF-1 is essential for Drosophila development and involved in the maintenance of epigenetic memory.

Y Song — 2007-10-25T00:36:51-00:00

Dev Biol, Vol. 311, No. 1. (1 November 2007), pp. 213-222.

DNA synthesis during S-phase and upon DNA repair is accompanied by chromatin assembly. The chromatin assembly factor CAF-1 has been biochemically well-characterized to deposit histones onto newly synthesized DNA. To gain insights into the in vivo functions of CAF-1 in Drosophila, we generated null mutants of the largest subunit of dCAF-1, dCAF-1-p180. We show that, unlike CAF-1 mutant yeast, dCAF-1-p180 mutant flies are hemizygous lethal. Removal of maternal dCAF-1-p180 activity by germline clones blocks oogenesis. Tissue-specific deletion of dCAF-1-p180 in the eye primordia disrupts eye development. In addition, reduction of dCAF-1-p180 activity suppresses gene silencing at heterochromatin and antagonizes Polycomb-mediated cell fate determination. Furthermore, heterozygous dCAF-1-p180 mutant flies display an increased sensitivity to gamma-irradiation and a reduced efficiency in recombinational double strand break (DSB) repair. Our experiments also show that human hCAF-1-p150 can rescue the dCAF-1-p180 mutant flies, demonstrating a functional conservation of eukaryotic CAF-1 activities in vivo. Together, our results establish that dCAF-1-p180 is an essential gene for Drosophila development and further underscore the importance of dCAF-1 in regulating gene expression and DNA repair in vivo.

X Chromosome Inactivation during Drosophila Spermatogenesis.

Winfried Hense — 2007-10-25T00:12:25-00:00

PLoS Biol, Vol. 5, No. 10. (9 October 2007)

Genes with male- and testis-enriched expression are under-represented on the Drosophila melanogaster X chromosome. There is also an excess of retrotransposed genes, many of which are expressed in testis, that have "escaped" the X chromosome and moved to the autosomes. It has been proposed that inactivation of the X chromosome during spermatogenesis contributes to these patterns: genes with a beneficial function late in spermatogenesis should be selectively favored to be autosomal in order to avoid inactivation. However, conclusive evidence for X inactivation in the male germline has been lacking. To test for such inactivation, we used a transgenic construct in which expression of a lacZ reporter gene was driven by the promoter sequence of the autosomal, testis-specific ocnus gene. Autosomal insertions of this transgene showed the expected pattern of male- and testis-specific expression. X-linked insertions, in contrast, showed only very low levels of reporter gene expression. Thus, we find that X linkage inhibits the activity of a testis-specific promoter. We obtained the same result using a vector in which the transgene was flanked by chromosomal insulator sequences. These results are consistent with global inactivation of the X chromosome in the male germline and support a selective explanation for X chromosome avoidance of genes with beneficial effects late in spermatogenesis.

The gap gene system of Drosophila melanogaster: Model-fitting and validation.

Theodore J Perkins — 2007-10-25T00:07:44-00:00

Ann N Y Acad Sci (12 October 2007)

The gap gene system of Drosophila melanogaster, part of the segmentation network, is one of the most well-known developmental gene networks. It is an ideal system for benchmarking the performance of network inference algorithms, due to the wealth and variety of data available and established knowledge of regulatory relationships controlling the system. We describe three recent efforts to fit wild-type spatio-temporal expression data, and to identify regulatory relationships between the genes de novo. These three efforts establish clear points of comparison regarding accuracy, correctness of regulatory architecture, and computational efficiency. We discuss the validation of these models against previous experimental work, and describe important directions for future research, including analysis of the less well understood pair-rule gene system, and relating promoter region composition with gene expression patterns and dynamics.

Global Analysis of mRNA Localization Reveals a Prominent Role in Organizing Cellular Architecture and Function

Eric Lecuyer — 2007-10-05T23:46:08-00:00

Cell, Vol. 131, No. 1. (5 October 2007), pp. 174-187.

Summary Although subcellular mRNA trafficking has been demonstrated as a mechanism to control protein distribution, it is generally believed that most protein localization occurs subsequent to translation. To address this point, we developed and employed a high-resolution fluorescent in situ hybridization procedure to comprehensively evaluate mRNA localization dynamics during early Drosophila embryogenesis. Surprisingly, of the 3370 genes analyzed, 71% of those expressed encode subcellularly localized mRNAs. Dozens of new and striking localization patterns were observed, implying an equivalent variety of localization mechanisms. Tight correlations between mRNA distribution and subsequent protein localization and function, indicate major roles for mRNA localization in nucleating localized cellular machineries. A searchable web resource documenting mRNA expression and localization dynamics has been established and will serve as an invaluable tool for dissecting localization mechanisms and for predicting gene functions and interactions.

Biological function of unannotated transcription during the early development of Drosophila melanogaster

Robert Manak — 2006-09-28T09:22:15-00:00

Nature Genetics, Vol. 38, No. 10. (03 September 2006), pp. 1151-1158.

Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses

Long Li — 2007-06-06T00:28:01-00:00

Genome Biology, Vol. 8 (05 June 2007), R101.

PIF-like Transposons Are Common in Drosophila and Have Been Repeatedly Domesticated to Generate New Host Genes.

Claudio Casola — 2007-06-29T04:50:07-00:00

Mol Biol Evol (7 June 2007)

The P instability factor or PIF superfamily of DNA transposons constitutes an important group of transposable elements (TEs) in plants, but it is still poorly characterized in metazoans. Taking advantage of the availability of draft genome sequences for twelve Drosophila species, we discovered four different lineages of Drosophila PIF-like transposons, named DPLT1-4. These lineages have experienced a complex evolutionary history during the Drosophila radiation, involving differential amplification and retention among species and probable events of horizontal transmission. Like previously described plant and animal PIF transposons, full-length DPLTs encode a putative transposase as well as a second predicted protein containing a Myb/SANT domain. In DPLTs, this domain is most closely related to the MADF DNA-binding domain found in several Drosophila transcription factors. In addition, we identified seven distinct genes distributed across the Drosophila genus that encode proteins related to PIF transposases, but lack the hallmarks of transposons. Instead, these sequences show features of functional genes, such as an intact coding region evolving under purifying selection, the presence of orthologs in at least two Drosophila species, and the conservation of intron/exon structure across orthologs. We also provide evidence that most of these genes are transcribed and that some are developmentally regulated. Together the data indicate that these genes derived from PIF-transposons that have been 'domesticated' to serve cellular functions. In one instance the recruitment of the transposase gene was accompanied by the co-recruitment of the adjacent second PIF gene, which raises the hypothesis that both proteins now function in the same pathway. The second PIF gene has retained the capacity to encode a protein with an intact MADF domain, suggesting that it may function as a transcription factor. We conclude that PIF transposons are common in the Drosophila lineage and have been a recurrent source of new genes during Drosophila evolution.

Life cycle transcriptome of the malaria mosquito Anopheles gambiae and comparison with the fruitfly Drosophila melanogaster

Anastasios Koutsos — 2007-06-12T09:28:56-00:00

PNAS (11 June 2007), 0703988104.

Contributed by Fotis C. Kafatos, May 10, 2007 (sent for review January 25, 2007)The African mosquito Anopheles gambiae is the major vector of human malaria. We report a genome-wide survey of mosquito gene expression profiles clustered temporally into developmental programs and spatially into adult tissue-specific patterns. Global expression analysis shows that genes that belong to related functional categories or that encode the same or functionally linked protein domains are associated with characteristic developmental programs or tissue patterns. Comparative analysis of our data together with data published from Drosophila melanogaster reveal an overall strong and positive correlation of developmental expression between orthologous genes. The degree of correlation varies, depending on association of orthologs with certain developmental programs or functional groups. Interestingly, the similarity of gene expression is not correlated with the coding sequence similarity of orthologs, indicating that expression profiles and coding sequences evolve independently. In addition to providing a comprehensive view of temporal and spatial gene expression during the A. gambiae life cycle, this large-scale comparative transcriptomic analysis has detected important evolutionary features of insect transcriptomes. 10.1073/pnas.0703988104

New candidate genes for sex comb divergence between Drosophila mauritiana and Drosophila simulans.

Rita M Graze — 2007-06-29T04:44:59-00:00

Genetics (11 June 2007)

A large effect QTL for divergence in sex comb tooth number between D. simulans and D. mauritiana was previously mapped to 73A-84AB. Here we identify genes that are likely contributors to this divergence. We first improved the mapping resolution in the 73A-84AB region using 12 introgression lines and 62 recombinant nearly isogenic lines. To further narrow the list of candidate genes, we assayed leg specific expression and identified genes with transcript level evolution consistent with a potential role in sex comb divergence. Sex combs are formed on the prothoracic (front) legs, but not on the mesothoracic (middle) legs of Drosophila males. We extracted RNA from the prothoracic and mesothoracic pupal legs of two species to determine which of the genes expressed differently between leg types were also divergent for gene expression. Two good functional candidate genes, Scr and dsx, are located in one of our fine-scale QTL regions. In addition, three previously uncharacterized genes (CG15186, CG2016, and CG2791) emerged as new candidates. These genes are located in regions strongly associated with sex comb tooth number differences and are expressed differently between leg tissues and between species. Further supporting the potential involvement of these genes in sex comb divergence, we found a significant difference in sex comb tooth number between co-isogenic lines with and without P element insertions at CG2791.

Genetics of incipient speciation in Drosophila mojavensis. I. Male courtship song, mating success, and genotype x environment interactions.

WJ Etges — 2007-06-14T22:22:41-00:00

Evolution Int J Org Evolution, Vol. 61, No. 5. (May 2007), pp. 1106-1119.

Few studies have examined genotype by environment (GxE) effects on premating reproductive isolation and associated behaviors, even though such effects may be common when speciation is driven by adaptation to different environments. In this study, mating success and courtship song differences among diverging populations of Drosophila mojavensis were investigated in a two-environment quantitative trait locus (QTL) analysis. Baja California and mainland Mexico populations of D. mojavensis feed and breed on different host cacti, so these host plants were used to culture F2 males to examine host-specific QTL effects and GxE interactions influencing mating success and courtship songs. Linear selection gradient analysis showed that mainland females mated with males that produced songs with significantly shorter L(long)-IPIs, burst durations, and interburst intervals. Twenty-one microsatellite loci distributed across all five major chromosomes were used to localize effects of mating success, time to copulation, and courtship song components. Male courtship success was influenced by a single detected QTL, the main effect of cactus, and four GxE interactions, whereas time to copulation was influenced by three different QTLs on the fourth chromosome. Multiple-locus restricted maximum likelihood (REML) analysis of courtship song revealed consistent effects linked with the same fourth chromosome markers that influenced time to copulation, a number of GxE interactions, and few possible cases of epistasis. GxE interactions for mate choice and song can maintain genetic variation in populations, but alter outcomes of sexual selection and isolation, so signal evolution and reproductive isolation may be slowed in diverging populations. Understanding the genetics of incipient speciation in D. mojavensis clearly depends on cactus-specific expression of traits associated with courtship behavior and sexual isolation.

Research on the karyotype and evolution of Drosophila melanogaster species group.

Q Deng — 2007-06-13T21:27:11-00:00

J Genet Genomics, Vol. 34, No. 3. (March 2007), pp. 196-213.

Mitotic metaphase chromosomes of 34 species of Drosophila melanogaster species group were examined. Certain new karyotypes were described for the first time, and their evolutionary and interspecific genetic relationships among 8 subgroups of D. melanogaster species group were analyzed systematically. The results were as follows. The basic karyotype of elegans subgroup was type A. The karyotypes of eugracilis subgroup, melanogaster subgroup, and ficusphila subgroup were all type C. The karyotypes of takahashii subgroup and suzukii subgroup were both type C and type D. The montium subgroup had six kinds of karyotypes: types B, C, C', D, D', and E. The ananassae subgroup had three kinds of karyotypes: types F, G, and H. Thus, the melanogaster species group was classified into five pedigrees based on the diversity of these karyotypes: 1) elegans; 2) eugracilis-melanogaster-ficusphila; 3) takkahashii-suzukii; 4) montium; 5) ananassae. The above-mentioned results in karyotypic evolution were consistent with those of DNA sequence analysis reported by Yang except for the elegans subgroup and this subgroup was considered as the ancestral subgroup. Karyotype analysis of the same drosophila from different isofemale lines indicated that the same Drosophila from different places showed karyotypic variation which might be due to different geographical environment and evolutionary degree or interaction between the two factors.

The stars and stripes of animal bodies: evolution of regulatory elements mediating pigment and bristle patterns in Drosophila.

Pat Simpson — 2007-06-13T21:24:48-00:00

Trends Genet (10 May 2007)

Evolution has generated enormous morphological diversity in animals and one of the genetic processes that might have contributed to this is evolution of the cis-regulatory sequences responsible for the temporal and spatial expression of genes regulating embryonic development. This could be particularly relevant to pleiotropic genes with multiple independently acting regulatory modules. Loss or gain of modules enables altered expression without loss of other functions. Here I focus on recent studies correlating differences in morphological traits between related species of Drosophila to changes in cis-regulatory sequences. They show that ancestral regulatory modules have evolved to mediate different transcriptional outputs and suggest that evolution of cis-regulatory sequences might reflect a general mechanism driving evolutionary change.