- Open Access
Segmental dataset and whole body expression data do not support the hypothesis that non-random movement is an intrinsic property of Drosophila retrogenes
© Vibranovski et al.; licensee BioMed Central Ltd. 2012
- Received: 23 March 2012
- Accepted: 24 August 2012
- Published: 5 September 2012
Several studies in Drosophila have shown excessive movement of retrogenes from the X chromosome to autosomes, and that these genes are frequently expressed in the testis. This phenomenon has led to several hypotheses invoking natural selection as the process driving male-biased genes to the autosomes. Metta and Schlötterer (BMC Evol Biol 2010, 10:114) analyzed a set of retrogenes where the parental gene has been subsequently lost. They assumed that this class of retrogenes replaced the ancestral functions of the parental gene, and reported that these retrogenes, although mostly originating from movement out of the X chromosome, showed female-biased or unbiased expression. These observations led the authors to suggest that selective forces (such as meiotic sex chromosome inactivation and sexual antagonism) were not responsible for the observed pattern of retrogene movement out of the X chromosome.
We reanalyzed the dataset published by Metta and Schlötterer and found several issues that led us to a different conclusion. In particular, Metta and Schlötterer used a dataset combined with expression data in which significant sex-biased expression is not detectable. First, the authors used a segmental dataset where the genes selected for analysis were less testis-biased in expression than those that were excluded from the study. Second, sex-biased expression was defined by comparing male and female whole-body data and not the expression of these genes in gonadal tissues. This approach significantly reduces the probability of detecting sex-biased expressed genes, which explains why the vast majority of the genes analyzed (parental and retrogenes) were equally expressed in both males and females. Third, the female-biased expression observed by Metta and Schlötterer is mostly found for parental genes located on the X chromosome, which is known to be enriched with genes with female-biased expression. Fourth, using additional gonad expression data, we found that autosomal genes analyzed by Metta and Schlötterer are less up regulated in ovaries and have higher chance to be expressed in meiotic cells of spermatogenesis when compared to X-linked genes.
The criteria used to select retrogenes and the sex-biased expression data based on whole adult flies generated a segmental dataset of female-biased and unbiased expressed genes that was unable to detect the higher propensity of autosomal retrogenes to be expressed in males. Thus, there is no support for the authors’ view that the movement of new retrogenes, which originated from X-linked parental genes, was not driven by selection. Therefore, selection-based genetic models remain the most parsimonious explanations for the observed chromosomal distribution of retrogenes.
- Dosage Compensation
- Drosophila Species
- Parental Copy
- Sexual Antagonism
- Segmental Dataset
In Drosophila, there is an excess of retrogenes moving from the X chromosome to autosomal regions . Interestingly, those retrogenes are frequently expressed in testis . Both observations have been reported several times in Drosophila melanogaster [1–3], as well as in other species of mammals  and mosquitoes [5, 6]. In addition, a comparative study between the genomes of twelve Drosophila species revealed excessive movement out of the X chromosome for both retrogenes and DNA-based duplications in the Drosophila genus [7, 8]. Further, older genes that originated before the split of the Drosophila and Sophophora subgenera and for which expression is greater in males than females, are under-represented on the X chromosome [9–12]. The gene movement off the X chromosome likely contributed, along with other mechanisms, to the paucity of X-linked male-biased genes found in Drosophila.
Several hypotheses have been proposed to explain the excessive movement of genes out of the X chromosome and the paucity of male-biased X-linked genes [1, 13–19]. These hypotheses include (i) meiotic sex chromosome inactivation (MSCI), (ii) dosage compensation, (iii) meiotic drive, and (iv) sexual antagonism, and they all assume that natural selection has favoured accumulation of male-biased genes on the autosomes [1, 13–19]. Two of those hypotheses, MSCI and dosage compensation, have been tested and shown to play a role in the genomic relocation of retrogenes expressed in testis [15, 16, 20]. MSCI is predicated on the hypothesis that retrogenes located on autosomes continue functioning during male meiosis whereas otherwise they would be subjected to inactivation [1, 17, 20]. Indeed, in meiosis where MSCI occurs, autosomal retrogenes have higher expression than their parental X-linked genes, presumably to compensate for their inactivation . In Drosophila, the dosage compensation hypothesis also predicts a decrease in the number of male-biased genes in the X chromosome relative to autosomes [15, 16]. Up-regulation in males is less effective for X-linked genes since they are already hypertranscribed during dosage compensation [15, 16]. Consistent with this hypothesis, autosomal retrogenes are often derived from X-linked parental genes that reside close to components of the dosage compensation machinery .
Reproduced from Table 2 in [
We revisited the analyses and sex-biased expression data presented by Metta and Schlötterer  and found several issues with the retrogene dataset and expression data used that tended to render their arguments arguable. First, we found that the set of retrogenes was a segmental dataset in which the majority of genes with male-biased expression were excluded. Second, we observed that the general unbiased expression they claimed to exist was actually a consequence of the use of expression data from whole animals. Sex-biased gene expression (particularly male-biased expression) is poorly revealed when RNA is obtained from whole-body samples in comparison to dissected tissues (gonads) [6, 7, 22]. Third, we found that most of the observed female-biased expression is derived from X-linked parental genes. The dataset provided by Metta and Schlötterer  shows an excess of X→A movement and therefore contains a significant number of parental genes that are located on the X chromosome, which is known to be enriched with female-biased genes. Fourth, we analyzed additional gonad expression data that support the evidence that autosomal genes show higher male-related expression than X-linked genes. In the following four sections, we report our analyses of Metta and Schlötterer’s  data that led to conclusions different from their previous ones.
The segmental dataset underestimated male-biased expression
We analyzed the dataset of positionally relocated genes for 12 Drosophila species , used by Metta and Schlötterer . Bhutkar et al. identified 46 cases of inter-chromosomal retrotransposition for which the parental copy had degenerated or had been lost (Methods). Metta and Schlötterer  further filtered the dataset by several criteria such as high coverage between orthologous sequence alignments and intron absence to control the data quality (filtered out 26 cases) . Therefore, for those remaining 20 cases together with a previously identified retrogene (RplP2), (herein named the segmental dataset), each of the 12 Drosophila species has only one orthologous gene that corresponds either to the parental gene or the retrogene. In Metta and Schlötterer’s study , D. melanogaster expression was retrieved from FlyAtlas  (which is based on comparison of gonad expression).
Nonetheless, Metta and Schlötterer  were aware that the testis expression data limited the analysis to D. melanogaster genes (no gonad expression data was available/used for other species). For the cases of retroposition where the parental gene had been lost, the copy present in D. melanogaster either corresponded to the parental gene or the retrogene, depending on which species or branch the duplication occurred. Using the segmental dataset and the expression criteria in , Metta and Schlötterer  found that only one out of five retrogenes located on an autosome is expressed (at very low levels) in the testis, which supported their argument for general female-biased or unbiased expression of retrogenes. However, this result was not consistent in Flyatlas  in which three of the five retrogenes (CG14286, CG12375, CG4918) are expressed in testis. Moreover, in the excluded dataset, the only case of an autosomal retrogene (CG10934) in D. melanogaster with parental X-linked gene is indeed testis-biased expressed .
The difference in sex-biased expression between the excluded and segmental datasets could have compromised their final conclusions , as one should expect that data subsets would not show drastic differences in expression patterns. One possibility is that the conservative sequence similarity used to construct the segmental dataset biased their acquisition of male-biased expressed genes since in Drosophila this class of genes is known to be more divergent than female-biased or unbiased expressed genes [26, 27].
However, the conservation of sequence similarity was not the only threshold used to remove genes from the segmental dataset . Other criteria, such as absence of introns, were also implemented . Therefore, it is possible that the segmental dataset represents an even more confident set of relocated retrogenes. Therefore, we conducted a full analysis on the excluded dataset (26 cases, see Additional file 2). We found no evidence to exclude the following cases: CG32119, CG14077, CG7557, CG8928, CG4904, CG14026 and CG12010. Note that three of those genes are male-biased expressed. Thus, those highly confident relocated genes contained in the excluded dataset still show a significantly higher frequency of male-biased genes than the segmental dataset (3 out of 7 vs. 0 out of 21 or 43% vs. 0%, Fisher Exact Test, p=0.0107). Nonetheless, we focused our further analyses only in the segmental dataset used by Metta and Schlötterer’s . In the following three sections, we present several points that led us to continue to have a different conclusion.
Whole-body gene expression comparison between males and females underestimated male-biased expression
The sex-biased expression data used by Metta and Schlötterer  came from a previously published article that compared whole body expression of males and females [11, 26], whereas previous analyses of gene movement with male expression in Drosophila utilized expression data from testes and ovaries [1–3]. It was reported that the number of genes with sex-biased expression is drastically reduced in the whole body expression data of D. melanogaster. We also have previously observed that analysis of gene duplicates using whole body expression data only recovered 30% of the male-biased gene expression in D. melanogaster gonads . This low coverage of male-biased genes in the whole body data was also observed in Anopheles gambiae[6, 22]. In this case an even smaller proportion of male-biased genes is observed when compared to the proportion of female-biased genes: only 7% of testis-biased expression is recovered using male whole-body RNA. In contrast, 50% of ovary-biased expression is recovered when using whole-body of females . Moreover, the number of female-biased genes can also be underestimated using whole-body RNA. Since those genes are widely expressed , the introduction of somatic tissues in the RNA pool may distort the relative excess found in the ovary. Therefore, the use of whole-body RNA underestimates in general detection of sex-biased genes found by gonadal tissue comparisons.
Metta and Schlötterer  also claimed that 60% of genes that have heterogeneous sex-biased expression, i.e. cases in which orthologs of the same gene in different species have different sex-biased expression. Moreover, they found that sex-biased expression among species show no particular pattern associated with retrogenes or parental copies (Table1). However, this result is not unexpected as only 11 out of the 41 retrogenes (27%) displayed sex-biased expression for all species/gene combinations (Figure2). We therefore reason that any conclusions regarding the relationship between sex-biased expression and chromosomal locations of retrogenes without parental genes must await additional studies using comparisons between gonads in males and females (see “Additional gonad expression data supports selection hypothesis for movement out of the X chromosome” below).
Female-biased expression is associated with X-linkage of parental genes
Metta and Schlötterer  claimed that genes in their dataset show a high frequency of female-biased expression in contrast to the male-biased expression usually found for retrogene moving out of the X chromosome. They interpreted this lack of association and the apparent non-random gene traffic off the X to reflect a non-adaptive process. However, we found that this level of female-biased expression (29/116 species/gene combinations, Tables1 and Figure2) is a consequence of large number of X-linked parental genes present in the dataset and therefore is not unexpected even under selection-driven models. In other words, there is an excess of the X-linked gene movement to the autosomes in their dataset. If all orthologs to the 21 retrogenes across the twelve Drosophila species are analyzed, it is clear that there will be an enrichment of X-linked parental genes when analyzing the total expression profile (80% vs. 20%, n = 119; Fisher’s Exact test, p < 0.0001). As the X chromosome in Drosophila is enriched with female-biased genes , it is reasonable to expect a high frequency of this class of gene.
Chromosomal distribution of female-biased genes
Additional gonad expression data supports selection hypothesis for movement out of the X chromosome
We searched for additional gonad expression data for the specific group of retrogenes and their parental counterparts analyzed by Metta and Schlötterer . If the selection is driving the retrogene movement out of the X chromosome, we should be able to detect lower expression in ovaries and higher expression in testis for those genes located in the autosomes in comparison to X-linked genes. However, if the movement out of the X chromosome is an intrinsic property of the retrogenes, no differences of sex-related expression should be expected.
Distribution of genes up regulated in ovary (FlyAtlas)
Second, using two different spermatogenic expression profiles [20, 29], we found that D. melanogaster autosomal genes described by Metta and Schlötterer  (entire dataset, n = 47) were more likely expressed in meiosis than in mitosis. Additional file 3: Figure S1 plots the correlation between two available expression profiles in D. melanogaster spermatogenesis [20, 29]. One of the profiles corresponds to the expression fold difference found between bag-of-marbles (bam) mutant and wild type testes . The bam mutation prevents the entry into meiosis stage and results in the accumulation of pre-meiotic cells . The other profile corresponds to the expression fold difference found between mitotic and meiotic cells dissected from wild-type testes . Both expression profiles are significantly correlated and therefore should reproduce the expression differences between the first two phases of spermatogenesis (r2 = 0.41, p = 2.3e-06). In the latter profile , the X-linked genes analyzed in Metta and Schlötterer’s  sample show a higher mitotic/meiotic expression when compared to genes located in the autosomes (t-test = 2.03, p = 0.048). This result suggests that autosomal genes are more frequently expressed in meiotic cells of the testis.
These independent analyses have shown that autosomal- and X-linked genes analyzed by Metta and Schlötterer  are not equally expressed regarding sex-related tissues: the autosomal genes tend to be less ovary-expressed and tend to show more male expression, more specifically the meiotic phases of the testis. This result is therefore in agreement with the hypothesis that selective forces such as MSCI, dosage compensation and sexual antagonism are involved in the retrogene movement out of the X chromosome [1, 13–17]. It is important to notice that the selective model does not necessarily require male-biased expression, but higher male expression of autosomal retrogenes than of their X-linked parental counterparts.
Numerous studies have shown increased testis expression of retrogenes that have moved out of the X chromosome in D. melanogaster[1–3, 7, 8]. Those findings are associated with several evolutionary hypotheses in which autosomal male-biased genes have been favoured by natural selection [1, 13–19]. However, the recent study of Metta and Schlötterer  found no evidence of male-biased expression among retrogenes for which the parental copy has been lost. On the contrary, the genes analyzed have mostly female-biased or unbiased expression . As those genes also show the excessive movement out of the X chromosome, Metta and Schlötterer  suggested that such a trend is an intrinsic property of retrogenes in Drosophila and not part of an adaptive process.
The segmental dataset used by Metta and Schlötterer  did not show the same proportion of testis-biased expressed genes observed in the entire dataset of retrogenes in which the parental gene was subsequently lost . Thus it is clear that the segmental dataset used by Metta and Schlötterer was not representative of the entire dataset of retrogenes for which the parental copy has been lost and the authors therefore took this as evidence against selection-based hypotheses .
In addition, statistical analysis of gene movement and sex chromosome evolution can only be performed using tissue-specific expression profiles across species, particularly male gonads [1–3, 6, 7, 9, 20]. However, such studies are complicated in cases where the parental copy has degenerated or has been lost. In those instances, movements of parent and retrogenes can only be inferred using genomic comparisons and phylogenetic inference between different Drosophila species [7, 8, 21, 23]. Unfortunately, expression data derived from gonad analysis do not yet exist for all genomic sequenced Drosophila species (only whole-body expression data has been assembled in ).
Although a previous study of whole-body expression analysis successfully detected the non-random chromosomal distribution of sex-biased genes , it failed to recover the known extensive male-biased expression obtained using tissue-specific data in D. melanogaster. That means whole-body expression analyses lack the statistical power needed to detect the tissue-specific basis of retrogene movement out of the X chromosome [7, 8] probably due to the smaller sample size of this dataset in comparison to genome-wide analyses. In a previous study , we approached this problem by using a conservative analysis of gene movement in D. melanogaster for which gonad expression data are available [7, 24]. Although the number of retrogenes was too small to conduct a statistical test, it was possible to show that X-linked parental genes for which the corresponding retrogene had moved to the autosomes were generally under-expressed in testis in agreement with sexual antagonism, MSCI and dosage compensation models . Thus, hypotheses concerning the generality of retrogene movements from the X (with or without parental genes) cannot be tested with existing expression data. We must await the acquisition of appropriate tissue-specific expression data from across the Drosophila clade.
However, we were able to show that there is an association of sex-biased expression with movement out of the X chromosome within the group of retrogenes analyzed by Metta and Schlötterer . First, using D. melanogaster gonad data from FlyAtlas , we found the X-linked parental genes tend to be more up regulated in ovaries than retrogenes located in the autosomes. Second, autosomal genes tend to more expressed in meiotic cells of the testis in comparison to X-linked genes. Those results are in agreement with the hypothesis that autosomal regions provide a favourable environment for male-expression [1, 13–19, 31].
Nevertheless, it is important to notice that even if the tissue-specific data across the Drosophila clade provides evidence for reduced testis-biased expression of retrogenes without parental genes compared to that of retrogenes with parental copies, it will not necessarily rule out MSCI, sexual antagonism, meiotic drive and dosage compensation models [1, 13–19]. The current sex-biased expression of retrogenes without parental gene does not necessary reflects expression levels when duplication occurred. In this model of retrotransposition, it is reasonable to assume that before the parental gene is lost, the retrogene would either complement the parental gene’s function, or undergo neo- or sub-functionalization . Only after degeneration of the parental copy could selection favour mutations in the retrogene that gradually restore the parental function . Therefore, for the selection-driven hypothesis, male-biased expression is only expected by the time the inter-chromosome movements have occurred.
In addition, there are several other lines of evidence supporting hypotheses that predict excessive gene movement off the X chromosome is driven by natural selection. First, the excessive gene movement out of the X chromosome is not exclusively found in retrogenes. Genes created by DNA-based mechanisms also show excessive out-of-the-X movement, which suggest that natural selection, rather than mutation processes intrinsic to retrotransposition, played an essential role in distributing male-biased genes [7, 8]. Second, chicken and silkworm, which have ZW sex determining systems, also present association between sex-bias gene expression and chromosomal gene movement. In those cases, a symmetrical pattern to the XY sex determining system is observed: genes that move out of the Z chromosome tend to be ovary-biased expressed [32, 33]. Therefore the phenomenon is not dependent on mutational processes intrinsic to the testis expression and therefore is more likely to be driven by natural selection. Third, a recent population genomic analysis of the copy number variants of Drosophila retrogenes found that there are more fixed than polymorphic retrogenes originating on the X chromosome, which provided direct and strong population genetic evidence for the positive selection hypotheses . Fourth, it worth mentioning that several autosomal retrogenes that moved out of the Drosophila X chromosome showing clear testis-specific functions have been indentified and extensively described. Examples of those genes are Drosophila nuclear transport factor-2-related (Dntf-2r), Rcd-1 related (Rcd-1r) and gasket (gskt), [1, 35–37].
Our re-analysis of Metta and Schlötterer’s  data mainly revealed that whole body expression analyses are unable to accurately assess sex-biased expression of retrogenes. A similar issue has been recently resolved in mosquitoes [5, 6]. The association between male-biased expression and Anopheles gambiae retrogene movement out of the X chromosome has been obscured by whole body data [5, 38], but revealed in experiments using dissected testes . The available evidence argues against Metta and Schlötterer’s  results and interpretations, and reanalysis of their data suggests that retrogenes with parental copies do not tend to be female-biased or unbiased in their expression. We therefore conclude that the excessive movement out of the X chromosome is not an intrinsic property of the retrogenes in Drosophila but instead the result of selective forces acting on males.
In conclusion, we note that the conclusions of Metta and Schlötterer  have been cited by others [39, 40]. It is the hope that our reanalysis of their work will serve to re-focus and clarify the importance of biological relevance in database construction and analysis of gene traffic in Drosophila. This is a crucial element to move forward in understanding the role of selection-driven hypotheses such as MSCI, dosage compensation, meiotic drive and sexual antagonism in sex chromosome evolution [1, 13–19].
Retrogene and parental gene identification
We retrieved the 47 genes analyzed by Metta and Schlötterer  from their Additional file 5. Those genes correspond to D. melanogaster genes involved in inter-chromosomal retrotransposition for which the parental copy had degenerated or had been lost, previously identified in . Following Metta and Schlötterer’s  classification, we separated those 47 inter-chromosomal gene movements into two sub-datasets here named by us as the segmental and the excluded datasets. The former contains 21 cases, which Metta and Schlötterer  selected by several criteria in order to control the data quality (see details in Additional file 1). The excluded dataset corresponds to the remaining 26 cases. In order to search for orthologs of the segmental dataset genes in other Drosophila species, we used the 21 D. melanogaster CGs as Flybase queries . Using the result from genome-wide drosophilid orthologs, we searched for GLEANR identifiers through the FlyBase FBgn-GLEANR ID Correspondence Table. GLEANR identifiers are listed in our Additional file 1.
Gene expression analysis
For the 21 gene movements presented in the segmental dataset, we searched for sex-biased pattern in male vs. female whole body comparisons in six Drosophila species . In order to reproduce expression data from Metta and Schlötterer  in non-D. melanogaster species, we used the GLEANR identifiers to search for male- and female-biased genes identified in Supplemental Tables 5–16 in . Genes that were not presented in those tables were considered as unbiased expressed genes between males and females.
Testis-biased expression profiles for D. melanogaster genes were obtained from Metta and Schlötterer  analysis marked in red both in Additional file 1 here and in Additional file 5 in . We re-analyzed the presence of expression in testis for all five retroposed copies in the segmental dataset that are located on the autosomes in D. melanogaster. Using the Affymetrix present call classification in FlyAtlas (4 out of 4 arrays), we observed that 3 out of the 5 retrogenes are expressed in testis in D. melanogaster as opposed to only one described in . D. melanogaster up regulation in ovary or testis in comparison to the whole body was also obtained from FlyAtlas  and is described in Additional file 1, Additional expression sheet.
Expression data on specific stages of D. melanogaster spermatogenesis was obtained from both bam mutant whole testes and from mitotic and meiotic phases of wild-type testes [20, 29]. Normalized expression data for the 47 D. melanogaster genes involved in gene movement were obtained from Tables S1 in [20, 29] by crosslinking Oligo identifiers and are described in Additional file 1.
In-house Perl scripts and unix commands were used to analyze different groups of data. Significances of the differences in 2x2 contingency tables were always assessed with Fisher’s exact tests as implemented in R.
We thank Robin M. Bush, Margarida Cardoso-Moreira and all members of the M. Long laboratory for helping with comments on the work. The authors were supported by a National Institutes of Health grant (NIH R0IGM078070-01A1), the NIH ARRA supplement grant (R01 GM078070-03S1), the Chicago Biomedical Consortium with support from The Searle Funds at The Chicago Community Trust, and a grant (No. O952B81P05) from the Key Laboratory of the Zoological Systematics and Evolution of the Chinese Academy of Sciences. NWV was partially supported by National Institutes of Health Grant T32 GM007197.
- Betrán E, Thornton K, Long M: Retroposed new genes out of the X in Drosophila. Genome Res. 2002, 12: 1854-1859. 10.1101/gr.6049.PubMedPubMed CentralView ArticleGoogle Scholar
- Bai Y, Casola C, Feschotte C, Betrán E: Comparative genomics reveals a constant rate of origination and convergent acquisition of functional retrogenes in Drosophila. Genome Biol. 2006, 8: R11-View ArticleGoogle Scholar
- Dai H, Yoshimatsu TF, Long M: Retrogene movement within- and between-chromosomes in the evolution of Drosophila genomes. Gene. 2006, 385: 96-102.PubMedView ArticleGoogle Scholar
- Emerson JJ, Kaessmann H, Betrán E, Long M: Extensive gene traffic on the mammalian X chromosome. Science. 2004, 303: 537-540. 10.1126/science.1090042.PubMedView ArticleGoogle Scholar
- Toups MA, Hahn MW: Retrogenes reveal the direction of sex-chromosome evolution in mosquitoes. Genetics. 2010, 186: 763-766. 10.1534/genetics.110.118794.PubMedPubMed CentralView ArticleGoogle Scholar
- Baker DA, Russell S: The role of testis-specific gene expression in sex chromosome evolution of Anopheles gambiae. Genetics. 2011, 189: 1117-1120. 10.1534/genetics.111.133157.PubMedPubMed CentralView ArticleGoogle Scholar
- Vibranovski MD, Zhang Y, Long M: General gene movement off the X chromosome in the Drosophila genus. Genome Res. 2009, 19: 897-903. 10.1101/gr.088609.108.PubMedPubMed CentralView ArticleGoogle Scholar
- Meisel RP, Han MV, Hahn MW: A Complex Suite of Forces Drives Gene Traffic from Drosophila X Chromosomes. Genome Biol Evol. 2009, 0: 176-188.Google Scholar
- Parisi M, Nuttall R, Naiman D, Bouffard G, Malley J, Andrews J, Eastman S, Oliver B: Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science. 2003, 299: 697-700. 10.1126/science.1079190.PubMedPubMed CentralView ArticleGoogle Scholar
- Ranz JM, Castillo-Davis CI, Meiklejohn CD, Hartl DL: Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science. 2003, 300: 1742-1745. 10.1126/science.1085881.PubMedView ArticleGoogle Scholar
- Sturgill D, Zhang Y, Parisi M, Oliver B: Demasculinization of X chromosomes in the Drosophila genus. Nature. 2007, 450: 238-241. 10.1038/nature06330.PubMedPubMed CentralView ArticleGoogle Scholar
- Zhang YE, Vibranovski MD, Krinsky BH, Long M: Age-dependent chromosomal distribution of male-biased genes in Drosophila. Genome Res. 2010, 20: 1526-1533. 10.1101/gr.107334.110.PubMedPubMed CentralView ArticleGoogle Scholar
- Rice WR: Sex chromosomes and the evolution of sexual dimorphism. Evolution. 1984, 38: 735-742. 10.2307/2408385.View ArticleGoogle Scholar
- Charlesworth B, Coyne AJ, Barton NH: The relative rates of evolution of sex chromosomes and autosomes. Am Nat. 1987, 130: 113-146. 10.1086/284701.View ArticleGoogle Scholar
- Vicoso B, Charlesworth B: The deficit of male-biased genes on the D. melanogaster X chromosome is expression-dependent: a consequence of dosage compensation?. J Mol Evol. 2009, 68: 576-583. 10.1007/s00239-009-9235-4.PubMedView ArticleGoogle Scholar
- Bachtrog D, Toda NR, Lockton S: Dosage compensation and demasculinization of X chromosomes in Drosophila. Curr Biol. 2010, 20: 1476-1481. 10.1016/j.cub.2010.06.076.PubMedPubMed CentralView ArticleGoogle Scholar
- Lifschytz E, Lindsley DL: The role of X-chromosome inactivation during spermatogenesis. Proc Nat Acad Sci USA. 1972, 69: 182-186. 10.1073/pnas.69.1.182.PubMedPubMed CentralView ArticleGoogle Scholar
- Tao Y, Masly JP, Araripe L, Ke Y, Hartl DL: A sex-ratio system in Drosophila simulans. I: An autosomal suppressor. PLoS Biol. 2007, 5: e292-10.1371/journal.pbio.0050292.PubMedPubMed CentralView ArticleGoogle Scholar
- Tao Y, Araripe L, Kingan SB, Ke Y, Xiao H, Hartl DL: A sex-ratio meiotic drive system in23 Drosophila simulans. II: An X-linked distorter. PLoS Biol. 2007, 5: e293-10.1371/journal.pbio.0050293.PubMedPubMed CentralView ArticleGoogle Scholar
- Vibranovski MD, Lopes HF, Karr TL, Long M: Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes. PLoS Genet. 2009, 5: e1000731-10.1371/journal.pgen.1000731.PubMedPubMed CentralView ArticleGoogle Scholar
- Metta M, Schlötterer C: Non-random genomic integration - an intrinsic property of retrogenes in Drosophila?. BMC Evol Biol. 2010, 10: 114-10.1186/1471-2148-10-114.PubMedPubMed CentralView ArticleGoogle Scholar
- Baker DA, Nolan T, Fischer B, Pinder A, Crisanti A, Russell S: A comprehensive gene expression atlas of sex- and tissue-specificity in the malaria vector. Anopheles gambiae. BMC Genomics. 2011, 12: 296-10.1186/1471-2164-12-296.PubMedPubMed CentralView ArticleGoogle Scholar
- Bhutkar A, Russo SM, Smith TF, Gelbart WM: Genome-scale analysis of positionally relocated genes. Genome Res. 2007, 17: 1880-1887. 10.1101/gr.7062307.PubMedPubMed CentralView ArticleGoogle Scholar
- Chintapalli VR, Wang J, Dow JA: Using FlyAtlas to identify better Drosophila melanogaster models of human disease. Nat Genet. 2007, 39: 715-720. 10.1038/ng2049.PubMedView ArticleGoogle Scholar
- Yanai I, Benjamin H, Shmoish M, Chalifa-Caspi V, Shklar M, Ophir R, Bar-Even A, Horn-Saban S, Safran M, Domany E, Lancet D, Shmueli O: Genomewide midrange transcription profiles reveal expression level relationships in human tissue specification. Bioinformatics. 2005, 21: 650-659. 10.1093/bioinformatics/bti042.PubMedView ArticleGoogle Scholar
- Zhang Y, Sturgill D, Parisi M, Kumar S, Oliver B: Constraint and turnover in sex-biased gene expression in the genus Drosophila. Nature. 2007, 450: 233-237. 10.1038/nature06323.PubMedPubMed CentralView ArticleGoogle Scholar
- Ellegren H, Parsch J: The evolution of sex-biased genes and sex-biased gene expression. Nature Rev Genet. 2007, 8: 689-698. 10.1038/nrg2167.PubMedView ArticleGoogle Scholar
- Wu C-I, Xu EY: Sexual antagonism and X inactivation–the SAXI hypothesis. Trends Genet. 2003, 19: 243-247. 10.1016/S0168-9525(03)00058-1.PubMedView ArticleGoogle Scholar
- Gan Q, Chepelev I, Wei G, Tarayrah L, Cui K, Zhao K, Chen X: Dynamic regulation of alternative splicing and chromatin structure in Drosophila gonads revealed by RNA-seq. Cell Res. 2010, 20 (7): 763-783. 10.1038/cr.2010.64.PubMedPubMed CentralView ArticleGoogle Scholar
- McKearin DM, Spradling AC: bag-of-marbles: a Drosophila Gene Required to Initiate Both Male and Female Gametogenesis. Genes Dev. 1990, 4: 2242-2251. 10.1101/gad.4.12b.2242.PubMedView ArticleGoogle Scholar
- Hense W, Baines JF, Parsch J: X chromosome inactivation during Drosophila spermatogenesis. PLoS Biol. 2007, 5: e273-10.1371/journal.pbio.0050273.PubMedPubMed CentralView ArticleGoogle Scholar
- Ellegren H: Emergence of male-biased genes on the chicken Z-chromosome: sex-chromosome contrasts between male and female heterogametic systems. Genome Res. 2011, 21: 2082-2086. 10.1101/gr.119065.110.PubMedPubMed CentralView ArticleGoogle Scholar
- Wang J, Long M, Vibranovski MD: Retrogenes Moved Out of the Z Chromosome in the Silkworm. J Mol Evol. 2012, in pressGoogle Scholar
- Schrider DR, Stevens K, Cardeño CM, Langley CH, Hahn MW: Genome-wide analysis of retrogene polymorphisms in Drosophila melanogaster. Genome Res. 2011, 21: 2087-2095. 10.1101/gr.116434.110.PubMedPubMed CentralView ArticleGoogle Scholar
- Betrán E, Long M: Dntf-2r, a young Drosophila retroposed gene with specific male expression under positive Darwinian selection. Genetics. 2003, 164: 977-988.PubMedPubMed CentralGoogle Scholar
- Quezada-Díaz JE, Muliyil T, Río J, Betrán E: Drcd-1 related: a positively selected spermatogenesis retrogene in Drosophila. Genetica. 2010, 138: 925-937. 10.1007/s10709-010-9474-8.PubMedPubMed CentralView ArticleGoogle Scholar
- Kalamegham R, Sturgill D, Siegfried E, Oliver B: Drosophila mojoless, a retroposed GSK-3, has functionally diverged to acquire an essential role in male fertility. Mol Biol Evol. 2007, 24: 732-742.PubMedPubMed CentralView ArticleGoogle Scholar
- Hahn MW, Lanzaro GC: Female-biased gene expression in the malaria mosquito Anopheles gambiae. Curr Biol. 2005, 15: R192-R193. 10.1016/j.cub.2005.03.005.PubMedView ArticleGoogle Scholar
- Mikhaylova LM, Nurminsky DI: Lack of global meiotic sex chromosome inactivation, and paucity of tissue-specific gene expression on the Drosophila X chromosome. BMC Biol. 2011, 9: 29-10.1186/1741-7007-9-29.PubMedPubMed CentralView ArticleGoogle Scholar
- Meiklejohn CD, Landeen EL, Cook JM, Kingan SB, Presgraves DC: Sex Chromosome-Specific Regulation in the Drosophila Male Germline But Little Evidence for Chromosomal Dosage Compensation or Meiotic Inactivation. PLoS Biology. 2011, 9: e100112-View ArticleGoogle Scholar
- Tweedie S, Ashburner M, Falls K, Leyland P, McQuilton P, Marygold S, Millburn G, Osumi-Sutherland D, Schroeder A, Seal R, Zhang H, The FlyBase Consortium: FlyBase: enhancing Drosophila Gene Ontology annotations. Nucleic Acids Research. 2009, 37: D555-D559. 10.1093/nar/gkn788.PubMedPubMed CentralView ArticleGoogle Scholar
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