Biomedical subjects

David J Begun

Publications and source records attributed to David J Begun.

At least 19 recordsLinked to original sources

PubMed2006

Novel genes derived from noncoding DNA in Drosophila melanogaster are frequently X-linked and exhibit testis-biased expression.

Descriptions of recently evolved genes suggest several mechanisms of origin including exon shuffling, gene fission/fusion, retrotransposition, duplication-divergence, and lateral gene transfer, all of which involve recruitment of preexisting genes or genetic elements into new function. The importance of noncoding DNA in the origin of novel genes remains an open question. We used the well annotated genome of the genetic model system Drosophila melanogaster and genome sequences of related species to carry out a whole-genome search for new D. melanogaster genes that are derived from noncoding DNA. Here, we describe five such genes, four of which are X-linked. Our RT-PCR experiments show that all five putative novel genes are expressed predominantly in testes. These data support the idea that these novel genes are derived from ancestral noncoding sequence and that new, favored genes are likely to invade populations under selective pressures relating to male reproduction.

Animals↗

PubMed2005

Recently evolved genes identified from Drosophila yakuba and D. erecta accessory gland expressed sequence tags.

The fraction of the genome associated with male reproduction in Drosophila may be unusually dynamic. For example, male reproduction-related genes show higher-than-average rates of protein divergence and gene expression evolution compared to most Drosophila genes. Drosophila male reproduction may also be enriched for novel genetic functions. Our earlier work, based on accessory gland protein genes (Acp's) in D. simulans and D. melanogaster, suggested that the melanogaster subgroup Acp's may be lost and/or gained on a relatively rapid timescale. Here we investigate this possibility more thoroughly through description of the accessory gland transcriptome in two melanogaster subgroup species, D. yakuba and D. erecta. A genomic analysis of previously unknown genes isolated from cDNA libraries of these species revealed several cases of genes present in one or both species, yet absent from ingroup and outgroup species. We found no evidence that these novel genes are attributable primarily to duplication and divergence, which suggests the possibility that Acp's or other genes coding for small proteins may originate from ancestrally noncoding DNA.

Animals↗

PubMed2005

Molecular population genetics of accessory gland protein genes and testis-expressed genes in Drosophila mojavensis and D. arizonae.

Molecular population genetic investigation of Drosophila male reproductive genes has focused primarily on melanogaster subgroup accessory gland protein genes (Acp's). Consistent with observations from male reproductive genes of numerous taxa, Acp's evolve more rapidly than nonreproductive genes. However, within the Drosophila genus, large data sets from additional types of male reproductive genes and from different species groups are lacking. Here we report findings from a molecular population genetics analysis of male reproductive genes of the repleta group species, Drosophila arizonae and D. mojavensis. We find that Acp's have dramatically higher average pairwise Ka/Ks (0.93) than testis-enriched genes (0.19) and previously reported melanogaster subgroup Acp's (0.42). Overall, 10 of 19 Acp's have Ka/Ks > 1 either in nonpolarized analyses or in at least one lineage of polarized analyses. Of the nine Acp's for which outgroup data were available, average Ka/Ks was considerably higher in D. mojavensis (2.08) than in D. arizonae (0.87). Contrasts of polymorphism and divergence suggest that adaptive protein evolution at Acp's is more common in D. mojavensis than in D. arizonae.

Animals↗

PubMed2005

Parallel evolution of chimeric fusion genes.

To understand how novel functions arise, we must identify common patterns and mechanisms shaping the evolution of new genes. Here, we take advantage of data from three Drosophila genes, jingwei, Adh-Finnegan, and Adh-Twain, to find evolutionary patterns and mechanisms governing the evolution of new genes. All three of these genes are independently derived from Adh, which enabled us to use the extensive literature on Adh in Drosophila to guide our analyses. We discovered a fundamental similarity in the temporal, spatial, and types of amino acid changes that occurred. All three genes underwent rapid adaptive amino acid evolution shortly after they were formed, followed by later quiescence and functional constraint. These genes also show striking parallels in which amino acids change in the Adh region. We showed that these early changes tend to occur at amino acid residues that seldom, if ever, evolve in Drosophila Adh. Changes at these slowly evolving sites are usually associated with loss of function or hypomorphic mutations in Drosophila melanogaster. Our data indicate that shifting away from ancestral functions may be a critical step early in the evolution of chimeric fusion genes. We suggest that the patterns we observed are both general and predictive.

Adaptation, Biological↗

PubMed2005

Rapid evolution of genomic Acp complement in the melanogaster subgroup of Drosophila.

Unusual properties of molecular evolution in reproduction-related Drosophila genes, including atypically rapid rates of protein evolution, support the idea that natural selection plays an important role in divergence of reproductive function in Drosophila. We used subtractive hybridization to investigate another potential side of evolution of the male reproductive transcriptome. We carried out a screen for genes with much greater transcript abundance in Drosophila simulans reproductive tracts than in Drosophila melanogaster reproductive tracts. Such genes could be present in both species but diverged dramatically in transcript abundance or could be present in D. simulans but absent from D. melanogaster. Here we report data from melanogaster subgroup species for three previously unknown accessory gland protein genes (Acps) identified in this screen. We found multiple Acps that were present in some lineages yet absent from other closely related melanogaster subgroup lineages, representing several losses of genes. An Acp that may have been lost in D. melanogaster and Drosophila erecta is segregating a null allele in Drosophila yakuba, yet shows evidence of adaptive protein evolution in contrasts of polymorphism and divergence within and between D. yakuba and its close relative, Drosophila teissieri. These data suggest that turnover of Acps occurs rapidly in Drosophila, consistent with rapid evolution of seminal fluid function.

Amino Acid Sequence↗

PubMed2005

Origin and evolution of a chimeric fusion gene in Drosophila subobscura, D. madeirensis and D. guanche.

An understanding of the mutational and evolutionary mechanisms underlying the emergence of novel genes is critical to studies of phenotypic and genomic evolution. Here we describe a new example of a recently formed chimeric fusion gene that occurs in Drosophila guanche, D. madeirensis, and D. subobscura. This new gene, which we name Adh-Twain, resulted from an Adh mRNA that retrotransposed into the Gapdh-like gene, CG9010. Adh-Twain is transcribed; its 5' promoters and transcription patterns appear similar to those of CG9010. Population genetic and phylogenetic analyses suggest that the amino acid sequence of Adh-Twain evolved rapidly via directional selection shortly after it arose. Its more recent history, however, is characterized by slower evolution consistent with increasing functional constraints. We present a model for the origin of this new gene and discuss genetic and evolutionary factors affecting the evolution of new genes and functions.

5' Untranslated Regions↗

PubMed2005

Evolutionary genomics: codon bias and selection on single genomes.

The idea that natural selection on genes might be detected using only a single genome has been put forward by Plotkin and colleagues, who present a method that they claim can detect selection without the need for comparative data and which, if correct, would confer greater power of analysis with less information. Here we argue that their method depends on assumptions that confound their conclusions and that, even if these assumptions were valid, the authors' inferences about adaptive natural selection are unjustified.

Bias↗

PubMed2005

Linkage disequilibrium and recent selection at three immunity receptor loci in Drosophila simulans.

Immune system genes in a California population sample of Drosophila simulans were shown to bear several hallmarks of the effects of past directional selection. One potential effect of directional selection is an increase in linkage disequilibrium among the polymorphic sites that are linked to the site under selection. In this study, we focus on three D. simulans immunity loci, Hmu, Sr-CI/Sr-CIII, and Tehao, for which the polymorphic sites are in nearly perfect linkage disequilibrium, an unusual finding even with respect to other immunity genes sampled from the same lines. The most likely explanation for this finding is that, at each locus, two divergent alleles have been selected to intermediate frequencies in the recent past. The extent to which the linkage disequilibrium extends to the flanks of each of the immunity genes is minimal, suggesting that the favored mutations actually occurred within the immunity genes themselves. Furthermore, the excess linkage disequilibrium found in the California population is not found in an African D. simulans population sample and may be a result of novel pathogen-mediated selection pressures encountered during establishment of non-African populations.

Animals↗

PubMed2005

A QTL analysis of female variation contributing to refractoriness and sperm competition in Drosophila melanogaster.

Sperm competition is an important fitness component in many animal groups. Drosophila melanogaster males exhibit substantial genetic variation for sperm competitive ability and females show considerable genetic variation for first versus second male sperm use. Currently, the forces responsible for maintaining genetic variation in sperm competition related phenotypes are receiving much attention. While several candidate genes contributing to the variation seen in male competitive ability are known, genes involved in female sperm use remain largely undiscovered. Without knowledge of the underlying genes, it will be difficult to distinguish between different models of sexual selection such as cryptic female choice and sexual conflict. We used quantitative trait locus (QTL) mapping to identify regions of the genome contributing to female propensity to use first or second male sperm, female refractoriness to re-mating, and early-life fertility. The most well supported markers influencing the phenotypes include 33F/34A (P2), 57B (refractoriness) and 23F/24A (fertility). Between 10% and 15% of the phenotypic variance observed in these recombinant inbred lines was explained by these individual QTLs. More detailed investigation of the regions detected in this experiment may lead to the identification of genes responsible for the QTLs identified here.

Animals↗

PubMed2004

Comparative genomics of accessory gland protein genes in Drosophila melanogaster and D. pseudoobscura.

Male accessory gland protein genes (Acps) evolve rapidly in the melanogaster species subgroup of Drosophila. However, conservation of Acps in more diverged lineages is poorly understood. We used comparisons of the D. melanogaster and D. pseudoobscura genome sequences, along with empirical investigation of D. pseudoobscura transcription, to assay the D. pseudoobscura genome for orthologs of 13 D. melanogaster Acps (Acp26Aa, Acp26Ab, Acp29AB, Acp32CD, Acp33A, Acp36DE, Acp53Ea, Acp62F, Acp63F, Acp70A, Acp76A, Acp95EF, and Acp98AB). We find that Acp26Aa, Acp26Ab, Acp32CD, and Acp53Ea are present at the expected microsyntenic locations of D. pseudoobscura. Acp62F and Acp70A are also present, although they are located in nonsyntenic regions. For six of the remaining seven Acps, computational and molecular biological evidence suggests they are D. melanogaster orphans. The weighted average of interspecific amino acid identity for alignable residues across the six orthologous Acps is 35.6%. Population genetic data for D. pseudoobscura Acp26Aa show that this gene has been evolving under directional selection, as it has been in D. melanogaster/D. simulans. All four D. melanogaster Acps we analyze from chromosome arm 3L are absent from the homologous D. pseudoobscura XR chromosome arm, which was autosomal before an X chromosome-autosome fusion event in the D. pseudoobscura lineage. This observation is consistent with the hypothesis that male-advantage genes on the Drosophila X chromosome are disfavored by natural selection.

Animals↗

PubMed2004

Patterns of polymorphism and divergence from noncoding sequences of Drosophila melanogaster and D. simulans: evidence for nonequilibrium processes.

Despite the fact that D. melanogaster and D. simulans have been the central model system for molecular population genetics, few data are available for noncoding regions. Here, we present an analysis of population genetic data from intergenic regions and comparisons of these data to previously collected data from introns and exons. Polymorphisms and fixations were categorized as A/T to G/C or G/C to A/T changes and were polarized by inferring the ancestral state using both parsimony and maximum likelihood. Noncoding fixations in both D. melanogaster and D. simulans were consistent with equilibrium base-composition evolution. However, polarized noncoding polymorphisms, revealed a different pattern. Although A/T to G/C and G/C to A/T polymorphisms in D. simulans were consistent with equilibrium, we observed a highly significant dearth of A/T to G/C polymorphisms in D. melanogaster introns but not in intergenic sequences. Such data could be explained by recent evolution of mutational biases associated with transcription or by lineage-specific selection on base composition. These data reveal the complexity of evolutionary processes acting even on noncoding DNA in Drosophila.

Animals↗

PubMed2004

Molecular evolution and population genetics of duplicated accessory gland protein genes in Drosophila.

To investigate the potential importance of gene duplication in D. melanogaster accessory gland protein (Acp) gene evolution we carried out a computational analysis comparing annotated D. melanogaster Acp genes to the entire D. melanogaster genome. We found that two known Acp genes are actually members of small multigene families. Polymorphism and divergence data from these duplicated genes suggest that in at least four cases, protein divergence between D. melanogaster and D. simulans is a result of directional selection. One putative Acp revealed by our computational analysis shows evidence of a recent selective sweep in a non-African population (but not in an African population). These data support the idea that selection on reproduction-related genes may drive divergence of populations within species, and strengthen the conclusion that Acps may often be under directional selection in Drosophila.

Amino Acid Sequence↗

PubMed2004

Strong selective sweep associated with a transposon insertion in Drosophila simulans.

We know little about several important properties of beneficial mutations, including their mutational origin, their phenotypic effects (e.g., protein structure changes vs. regulatory changes), and the frequency and rapidity with which they become fixed in a population. One signature of the spread of beneficial mutations is the reduction of heterozygosity at linked sites. Here, we present population genetic data from several loci across chromosome arm 2R in Drosophila simulans. A 100-kb segment from a freely recombining region of this chromosome shows extremely reduced heterozygosity in a California population sample, yet typical levels of divergence between species, suggesting that at least one episode of strong directional selection has occurred in the region. The 5' flanking sequence of one gene in this region, Cyp6g1 (a cytochrome P450), is nearly fixed for a Doc transposable element insertion. Presence of the insertion is correlated with increased transcript abundance of Cyp6g1, a phenotype previously shown to be associated with insecticide resistance in Drosophila melanogaster. Surveys of nucleotide variation in the same genomic region in an African D. simulans population revealed no evidence for a high-frequency Doc element and no evidence for reduced polymorphism. These data are consistent with the notion that the Doc element is a geographically restricted beneficial mutation. Data from D. simulans Cyp6g1 are paralleled in many respects by data from its sister species D. melanogaster.

Animals↗

PubMed2004

A genome-wide analysis of courting and mating responses in Drosophila melanogaster females.

In Drosophila melanogaster, seminal fluid proteins influence several components of female physiology and behavior, including re-mating rates, ovulation and oviposition, and sperm use. It is well-known that female flies are not simply passive vessels and that female-mediated interactions with male products are important to female (and thus male) reproductive success. While the population genetics, molecular evolution and physiological effects of seminal fluid proteins have been examined, the genetics and evolution of the female side of these post-mating interactions is unexplored in spite of work showing that female genotype and female-by-male genotype interactions are important determinants of sperm competition outcomes. Here we use microarrays to identify candidate genes involved in the female side of post-mating sexual interactions. We report the results of a whole-genome oligonucleotide chip experiment that reveals 23 genes differentially expressed between virgin females exposed and unexposed to courting males, and 38 genes differentially expressed between virgin and recently mated females. Immune related genes are overrepresented among the mating-influenced candidates. We use quantitative reverse-transcriptase PCR to independently assess gene expression changes for roughly half of the mating-affected candidate genes.

Animals↗

PubMed2004

Molecular population genetics of male accessory gland proteins in the Drosophila simulans complex.

Accessory gland proteins are a major component of Drosophila seminal fluid. These proteins have a variety of functions and may be subject to sexual selection and/or antagonistic evolution between the sexes. Most population genetic data from these proteins are from D. melanogaster and D. simulans. Here, we extend the population genetic analysis of Acp genes to the other simulans complex species, D. mauritiana and D. sechellia. We sequenced population samples of seven Acp's from D. mauritiana, D. sechellia, and D. simulans. We investigated the population genetics of these genes on individual simulans complex lineages and compared Acp polymorphism and divergence to polymorphism and divergence from a set of non-Acp loci in the same species. Polymorphism and divergence data from the simulans complex revealed little evidence for adaptive protein evolution at individual loci. However, we observed a dramatically inflated index of dispersion for amino acid substitutions in the simulans complex at Acp genes, but not at non-Acp genes. This pattern of episodic bursts of protein evolution in Acp's provides the strongest evidence to date that the population genetic mechanisms driving Acp divergence are different from the mechanisms driving evolution at most Drosophila genes.

Animals↗

PubMed2003

Natural selection drives Drosophila immune system evolution.

Evidence from disparate sources suggests that natural selection may often play a role in the evolution of host immune system proteins. However, there have been few attempts to make general population genetic inferences on the basis of analysis of several immune-system-related genes from a single species. Here we present DNA polymorphism and divergence data from 34 genes thought to function in the innate immune system of Drosophila simulans and compare these data to those from 28 nonimmunity genes sequenced from the same lines. Several statistics, including average K(A)/K(S) ratio, average silent heterozygosity, and average haplotype diversity, significantly differ between the immunity and nonimmunity genes, suggesting an important role for directional selection in immune system protein evolution. In contrast to data from mammalian immunoglobulins and other proteins, we find no strong evidence for the selective maintenance of protein diversity in Drosophila immune system proteins. This may be a consequence of Drosophila's generalized innate immune response.

Animals↗

PubMed2002

Molecular population genetics of Xdh and the evolution of base composition in Drosophila.

Few loci have been measured for DNA polymorphism and divergence in several species. Here we report such data from the protein-coding region of xanthine dehydrogenase (Xdh) in 22 species of Drosophila. Many of our samples were from closely related species, allowing us to confidently assign substitutions to individual lineages. Surprisingly, Xdh appears to be fixing more A/T mutations than G/C mutations in most lineages, leading to evolution of higher A/T content in the recent past. We found no compelling evidence for selection on protein variation, though some aspects of the data support the notion that a significant fraction of amino acid polymorphisms are slightly deleterious. Finally, we found no convincing evidence that levels of silent heterozygosity are associated with rates of protein evolution.

Amino Acid Substitution↗

PubMed2002

Genomic effects of nucleotide substitutions in Drosophila simulans.

Selective fixation of beneficial mutations reduces levels of linked, neutral variation. The magnitude of this "hitchhiking effect" is determined by the strength of selection and the recombination rate between selected and neutral sites. Thus, depending on the values of these parameters and the frequency with which directional selection occurs, the genomic scale over which directional selection reduces levels of linked variation may vary widely. Here we present a permutation-based analysis of nucleotide polymorphisms and fixations in Drosophila simulans. We show evidence of pervasive small-scale hitchhiking effects in this lineage. Furthermore, our results reveal that different types of fixations are associated with different levels of linked variation.

Animals↗