Effects of X-Linkage and Sex-Biased Gene Expression on the Rate of Adaptive Protein Evolution in Drosophila

Patterns of polymorphism and divergence in Drosophila protein-coding genes suggest that a considerable fraction of amino acid differences between species can be attributed to positive selection and that genes with sex-biased expression, that is, those expressed predominantly in one sex, have especially high rates of adaptive evolution. Previous studies, however, have been restricted to autosomal sex-biased genes and, thus, do not provide a complete picture of the evolutionary forces acting on sex-biased genes across the genome. To determine the effects of X-linkage on sex-biased gene evolution, we surveyed DNA sequence polymorphism and divergence in 45 X-linked genes, including 17 with male-biased expression, 13 with female-biased expression, and 15 with equal expression in the 2 sexes. Using both single- and multilocus tests for selection, we found evidence for adaptive evolution in both groups of sex-biased genes. The signal of adaptive evolution was particularly strong for X-linked male-biased genes. A comparison with data from 91 autosomal genes revealed a ‘‘fast-X’’ effect, in which the rate of adaptive evolution was greater for X-linked than for autosomal genes. This effect was strongest for male-biased genes but could be seen in the other groups as well. A genome-wide analysis of coding sequence divergence that accounted for sex-biased expression also uncovered a fast-X effect for male-biased and unbiased genes, suggesting that recessive beneficial mutations play an important role in adaptation.Organismic and Evolutionary Biolog

Both Size and GC-Content of Minimal Introns Are Selected in Human Populations

Background: We previously have studied the insertion and deletion polymorphism by sequencing no more than one hundred introns in a mixed human population and found that the minimal introns tended to maintain length at an optimal size. Here we analyzed re-sequenced 179 individual genomes (from African, European, and Asian populations) from the data released by the 1000 Genome Project to study the size dynamics of minimal introns. Principal Findings: We not only confirmed that minimal introns in human populations are selected but also found two major effects in minimal intron evolution: (i) Size-effect: minimal introns longer than an optimal size (87 nt) tend to have a higher ratio of deletion to insertion than those that are shorter than the optimal size; (ii) GC-effect: minimal introns with lower GC content tend to be more frequently deleted than those with higher GC content. The GC-effect results in a higher GC content in minimal introns than their flanking exons as opposed to larger introns ($125 nt) that always have a lower GC content than that of their flanking exons. We also observed that the two effects are distinguishable but not completely separable within and between populations. Conclusions: We validated the unique mutation dynamics of minimal introns in keeping their near-optimal size and GC content, and our observations suggest potentially important functions of human minimal introns in transcript processin

X Chromosome Inactivation during Drosophila Spermatogenesis

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

Population transcriptomics of Drosophila melanogaster females

<p>Abstract</p> <p>Background</p> <p>Variation at the level of gene expression is abundant in natural populations and is thought to contribute to the adaptive divergence of populations and species. Gene expression also differs considerably between males and females. Here we report a microarray analysis of gene expression variation among females of 16 <it>Drosophila </it><it>melanogaster </it>strains derived from natural populations, including eight strains from the putative ancestral range in sub-Saharan Africa and eight strains from Europe. Gene expression variation among males of the same strains was reported previously.</p> <p>Results</p> <p>We detected relatively low levels of expression polymorphism within populations, but much higher expression divergence between populations. A total of 569 genes showed a significant expression difference between the African and European populations at a false discovery rate of 5%. Genes with significant over-expression in Europe included the insecticide resistance gene <it>Cyp6g1</it>, as well as genes involved in proteolysis and olfaction. Genes with functions in carbohydrate metabolism and vision were significantly over-expressed in the African population. There was little overlap between genes expressed differently between populations in females and males.</p> <p>Conclusions</p> <p>Our results suggest that adaptive changes in gene expression have accompanied the out-of-Africa migration of <it>D. melanogaster</it>. Comparison of female and male expression data indicates that the vast majority of genes differing in expression between populations do so in only one sex and suggests that most regulatory adaptation has been sex-specific.</p

Decoding of Superimposed Traces Produced by Direct Sequencing of Heterozygous Indels

Direct Sanger sequencing of a diploid template containing a heterozygous insertion or deletion results in a difficult-to-interpret mixed trace formed by two allelic traces superimposed onto each other. Existing computational methods for deconvolution of such traces require knowledge of a reference sequence or the availability of both direct and reverse mixed sequences of the same template. We describe a simple yet accurate method, which uses dynamic programming optimization to predict superimposed allelic sequences solely from a string of letters representing peaks within an individual mixed trace. We used the method to decode 104 human traces (mean length 294 bp) containing heterozygous indels 5 to 30 bp with a mean of 99.1% bases per allelic sequence reconstructed correctly and unambiguously. Simulations with artificial sequences have demonstrated that the method yields accurate reconstructions when (1) the allelic sequences forming the mixed trace are sufficiently similar, (2) the analyzed fragment is significantly longer than the indel, and (3) multiple indels, if present, are well-spaced. Because these conditions occur in most encountered DNA sequences, the method is widely applicable. It is available as a free Web application Indelligent at http://ctap.inhs.uiuc.edu/dmitriev/indel.asp

Elastic Stable Intramedullary Nailing (ESIN), Orthoss® and Gravitational Platelet Separation - System (GPS®): An effective method of treatment for pathologic fractures of bone cysts in children

<p>Abstract</p> <p>Background</p> <p>The different treatment strategies for bone cysts in children are often associated with persistence and high recurrence rates of the lesions. The safety and clinical outcomes of a combined mechanical and biological treatment with elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma are evaluated.</p> <p>Methods</p> <p>From 02/07 to 01/09 we offered all children with bone cysts the treatment combination of elastic intramedullary nailing (ESIN), artificial bone substitute (Orthoss^®) and autologous platelet rich plasma, concentrated by the Gravitational Platelet Separation (GPS^®) - System. All patients were reviewed radiologically for one year following the removal of the intramedullary nailing, which was possible because of cyst obliteration.</p> <p>Results</p> <p>A cohort of 12 children (4 girls, 8 boys) was recruited. The mean patient age was 11.4 years (range 7-15 years). The bone defects (ten humeral, two femoral) included eight juvenile and four aneurysmal bone cysts. Five patients suffered from persistent cysts following earlier unsuccessful treatment of humeral bone cyst after pathologic fracture; the other seven presented with acute pathologic fractures. No peri- or postoperative complications occurred. The radiographic findings showed a total resolution of the cysts in ten cases (Capanna Grade 1); in two cases a small residual cyst remained (Capanna Grade 2). The intramedullary nails were removed six to twelve months (mean 7.7) after the operation; in one case, a fourteen year old boy (Capanna Grade 2), required a further application of GPS^®and Orthoss^®to reach a total resolution of the cyst. At follow-up (20-41 months, mean 31.8 months) all patients showed very good functional results and had returned to sporting activity. No refracture occurred, no further procedure was necessary.</p> <p>Conclusions</p> <p>The combination of elastic intramedullary nailing, artificial bone substitute and autologous platelet rich plasma (GPS^®) enhances the treatment of bone cysts in children, with no resulting complications.</p

Radiolucent lines in low-contact-stress mobile-bearing total knee arthroplasty: a blinded and matched case control study

<p>Abstract</p> <p>Background</p> <p>Low-contact-stress (LCS) mobile-bearing total knee arthroplasty (TKA) (Johnson & Johnson, New Brunswick, NJ; previously: DePuy, Warsawa, USA) provides excellent functional results and wear rates in long-term follow-up analyses. Radiological analysis shows radiolucent lines (RLL) appearing immediately or two years after primary implantation, indicative of poor seat. Investigations proved RLL to be more frequent in uncemented TKA, resulting in a consensus to cement the tibial plateau, but their association with clinical findings and patients discomfort and knee pain is still unknown.</p> <p>Methods</p> <p>553 patients with 566 low-contact-stress (LCS) total knee prostheses were screened for continuous moderate knee pain. We compared tibial stress shielding classified by Ewald in patients suffering from pain with a matched, pain-free control group on blinded X-rays. We hypothesized a positive correlation between pain and radiolucency and higher frequency of such radiolucent lines in the most medial and most lateral zones of the tibial plateau.</p> <p>Results</p> <p>Twenty-eight patients suffered from knee pain in total. Radiolucencies were detected in 27 of these cases and in six out of 28 matched controls without knee pain. We could demonstrate a significant correlation of knee pain and radiolucencies, which appeared significantly more frequently in the outermost zones of the tibial plateau.</p> <p>Conclusion</p> <p>Our findings suggest that radiolucent lines, representing poor implant seat, about the tibial plateau are associated with knee pain in LCS patients. Radiolucencies are observed more often in noncemented LCS, and cementing the tibial plateau might improve implant seat and reduce both radiolucent lines and associated knee pain.</p

Genomic analysis of Sparus aurata reveals the evolutionary dynamics of sex-biased genes in a sequential hermaphrodite fish

Sexual dimorphism is a fascinating subject in evolutionary biology and mostly results from sex-biased expression of genes, which have been shown to evolve faster in gonochoristic species. We report here genome and sex-specific transcriptome sequencing of Sparus aurata, a sequential hermaphrodite fish. Evolutionary comparative analysis reveals that sex-biased genes in S. aurata are similar in number and function, but evolved following strikingly divergent patterns compared with gonochoristic species, showing overall slower rates because of stronger functional constraints. Fast evolution is observed only for highly ovary-biased genes due to female-specific patterns of selection that are related to the peculiar reproduction mode of S. aurata, first maturing as male, then as female. To our knowledge, these findings represent the first genome-wide analysis on sex-biased loci in a hermaphrodite vertebrate species, demonstrating how having two sexes in the same individual profoundly affects the fate of a large set of evolutionarily relevant genes.European Union KBBE.2013.1.2-10 European Community 311920 Fondazione Cassa di Risparmio Padova e Rovigo FCT - Foundation for Science and Technology research grant SPARCOMP under the Call ARISTEIA I of the National Strategic Reference Framework - by the EU 36 Hellenic Republic through the European Social Fundinfo:eu-repo/semantics/publishedVersio