Complex Interplay of Evolutionary Forces in the ladybird Homeobox Genes of Drosophila melanogaster

Tandemly arranged paralogous genes lbe and lbl are members of the Drosophila NK homeobox family. We analyzed population samples of Drosophila melanogaster from Africa, Europe, North and South America, and single strains of D. sechellia, D. simulans, and D. yakuba within two linked regions encompassing partial sequences of lbe and lbl. The evolution of lbe and lbl is highly constrained due to their important regulatory functions. Despite this, a variety of forces have shaped the patterns of variation in lb genes: recombination, intragenic gene conversion and natural selection strongly influence background variation created by linkage disequilibrium and dimorphic haplotype structure. The two genes exhibited similar levels of nucleotide diversity and positive selection was detected in the noncoding regions of both genes. However, synonymous variability was significantly higher for lbe: no nonsynonymous changes were observed in this gene. We argue that balancing selection impacts some synonymous sites of the lbe gene. Stability of mRNA secondary structure was significantly different between the lbe (but not lbl) haplotype groups and may represent a driving force of balancing selection in epistatically interacting synonymous sites. Balancing selection on synonymous sites may be the first, or one of a few such observations, in Drosophila. In contrast, recurrent positive selection on lbl at the protein level influenced evolution at three codon sites. Transcription factor binding-site profiles were different for lbe and lbl, suggesting that their developmental functions are not redundant. Combined with our previous results on nucleotide variation in esterase and other homeobox genes, these results suggest that interplay of balancing and directional selection may be a general feature of molecular evolution in Drosophila and other eukaryote genomes

PseudoGeneQuest – Service for identification of different pseudogene types in the human genome

<p>Abstract</p> <p>Background</p> <p>Pseudogenes, nonfunctional copies of genes, evolve fast due the lack of evolutionary pressures and thus appear in several different forms. PseudoGeneQuest is an online tool to search the human genome for a given query sequence and to identify different types of pseudogenes as well as novel genes and gene fragments.</p> <p>Description</p> <p>The service can detect pseudogenes, that have arisen either by retrotransposition or segmental genome duplication, many of which are not listed in the public pseudogene databases. The service has a user-friendly web interface and uses a powerful computer cluster in order to perform parallel searches and provide relatively fast runtimes despite exhaustive database searches and analyses.</p> <p>Conclusion</p> <p>PseudoGeneQuest is a versatile tool for detecting novel pseudogene candidates from the human genome. The service searches human genome sequences for five types of pseudogenes and provides an output that allows easy further analysis of observations. In addition to the result file the system provides visualization of the results linked to Ensembl Genome Browser. PseudoGeneQuest service is freely available.</p

Symbiotic Associations in the Phenotypically-Diverse Brown Alga Saccharina japonica

The brown alga Saccharina japonica (Areschoug) Lane, Mayes, Druehl et Saunders is a highly polymorphic representative of the family Laminariaceae, inhabiting the northwest Pacific region. We have obtained 16S rRNA sequence data in symbiont microorganisms of the typical form (TYP) of S. japonica and its common morphological varieties, known as “longipes” (LON) and “shallow-water” (SHA), which show contrasting bathymetric distribution and sharp morphological, life history traits, and ecological differences. Phylogenetic analysis of the 16S rRNA sequences shows that the microbial communities are significantly different in the three forms studied and consist of mosaic sets of common and form-specific bacterial lineages. The divergence in bacterial composition is substantial between the TYP and LON forms in spite of their high genetic similarity. The symbiont distribution in the S. japonica forms and in three other laminarialean species is not related to the depth or locality of the algae settlements. Combined with our previous results on symbiont associations in sea urchins and taking into account the highly specific character of bacteria-algae associations, we propose that the TYP and LON forms may represent incipient species passing through initial steps of reproductive isolation. We suggest that phenotype differences between genetically similar forms may be caused by host-symbiont interactions that may be a general feature of evolution in algae and other eukaryote organisms. Bacterial symbionts could serve as sensitive markers to distinguish genetically similar algae forms and also as possible growth-promoting inductors to increase algae productivity

Bringing Molecules Back into Molecular Evolution

Much molecular-evolution research is concerned with sequence analysis. Yet these sequences represent real, three-dimensional molecules with complex structure and function. Here I highlight a growing trend in the field to incorporate molecular structure and function into computational molecular-evolution work. I consider three focus areas: reconstruction and analysis of past evolutionary events, such as phylogenetic inference or methods to infer selection pressures; development of toy models and simulations to identify fundamental principles of molecular evolution; and atom-level, highly realistic computational modeling of molecular structure and function aimed at making predictions about possible future evolutionary events

Comparative Genomics of Bordetella pertussis Reveals Progressive Gene Loss in Finnish Strains

BACKGROUND: Bordetella pertussis is a gram-negative bacterium that infects the human respiratory tract and causes pertussis or whooping cough. The disease has resurged in many countries including Finland where the whole-cell pertussis vaccine has been used for more than 50 years. Antigenic divergence has been observed between vaccine strains and clinical isolates in Finland. To better understand genome evolution in B. pertussis circulating in the immunized population, we developed an oligonucleotide-based microarray for comparative genomic analysis of Finnish strains isolated during the period of 50 years. METHODOLOGY/PRINCIPAL FINDINGS: The microarray consisted of 3,582 oligonucleotides (70-mer) and covered 94% of 3,816 ORFs of Tohama I, the strain of which the genome has been sequenced. Twenty isolates from 1953 to 2004 were studied together with two Finnish vaccine strains and two international reference strains. The isolates were selected according to their characteristics, e.g. the year and place of isolation and pulsed-field gel electrophoresis profiles. Genomic DNA of the tested strains, along with reference DNA of Tohama I strain, was labelled and hybridized. The absence of genes as established with microarrays, was confirmed by PCR. Compared with the Tohama I strain, Finnish isolates lost 7 (8.6 kb) to 49 (55.3 kb) genes, clustered in one to four distinct loci. The number of lost genes increased with time, and one third of lost genes had functions related to inorganic ion transport and metabolism, or energy production and conversion. All four loci of lost genes were flanked by the insertion sequence element IS481. CONCLUSION/SIGNIFICANCE: Our results showed that the progressive gene loss occurred in Finnish B. pertussis strains isolated during a period of 50 years and confirmed that B. pertussis is dynamic and is continuously evolving, suggesting that the bacterium may use gene loss as one strategy to adapt to highly immunized populations

Comparative genomic analysis of the arthropod muscle myosin heavy chain genes allows ancestral gene reconstruction and reveals a new type of 'partially' processed pseudogene

<p>Abstract</p> <p>Background</p> <p>Alternative splicing of mutually exclusive exons is an important mechanism for increasing protein diversity in eukaryotes. The insect <it>Mhc </it>(myosin heavy chain) gene produces all different muscle myosins as a result of alternative splicing in contrast to most other organisms of the Metazoa lineage, that have a family of muscle genes with each gene coding for a protein specialized for a functional niche.</p> <p>Results</p> <p>The muscle myosin heavy chain genes of 22 species of the Arthropoda ranging from the waterflea to wasp and <it>Drosophila </it>have been annotated. The analysis of the gene structures allowed the reconstruction of an ancient muscle myosin heavy chain gene and showed that during evolution of the arthropods introns have mainly been lost in these genes although intron gain might have happened in a few cases. Surprisingly, the genome of <it>Aedes aegypti </it>contains another and that of <it>Culex pipiens quinquefasciatus </it>two further muscle myosin heavy chain genes, called <it>Mhc3 </it>and <it>Mhc4</it>, that contain only one variant of the corresponding alternative exons of the <it>Mhc1 </it>gene. <it>Mhc3 </it>transcription in <it>Aedes aegypti </it>is documented by EST data. <it>Mhc3 </it>and <it>Mhc4 </it>inserted in the <it>Aedes </it>and <it>Culex </it>genomes either by gene duplication followed by the loss of all but one variant of the alternative exons, or by incorporation of a transcript of which all other variants have been spliced out retaining the exon-intron structure. The second and more likely possibility represents a new type of a 'partially' processed pseudogene.</p> <p>Conclusion</p> <p>Based on the comparative genomic analysis of the alternatively spliced arthropod muscle myosin heavy chain genes we propose that the splicing process operates sequentially on the transcript. The process consists of the splicing of the mutually exclusive exons until one exon out of the cluster remains while retaining surrounding intronic sequence. In a second step splicing of introns takes place. A related mechanism could be responsible for the splicing of other genes containing mutually exclusive exons.</p

MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

<p>Abstract</p> <p>Background</p> <p>Mitochondrial DNA (mtDNA) mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified.</p> <p>Methods</p> <p>With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (<it>DEFA3 </it>gene absence, <it>CLDN23 </it>gene and <it>MRPS18CP2 </it>pseudogene) in a group of 213 A1555G carriers.</p> <p>Results</p> <p>Family based association studies identified a positive association for a polymorphism on <it>MRPS18CP2 </it>and an overrepresentation of <it>DEFA3 </it>gene absence in the deaf group of A1555G carriers.</p> <p>Conclusion</p> <p>Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.</p

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

BACKGROUND: Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. METHODS: We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. RESULTS: First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10-4; replication: ORint = 1.40, p = 0.03). CONCLUSIONS: Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma

Regional Selection Acting on the OFD1 Gene Family

The OFD1 (oral-facial-digital, type 1) gene is implicated in several developmental disorders in humans. The X-linked OFD1 (OFD1X) is conserved in Eutheria. Knowledge about the Y-linked paralog (OFD1Y) is limited. In this study, we identified an OFD1Y on the bovine Y chromosome, which is expressed differentially from the bovine OFD1X. Phylogenetic analysis indicated that: a) the eutherian OFD1X and OFD1Y were derived from the pair of ancestral autosomes during sex chromosome evolution; b) the autosomal OFD1 pseudogenes, present in Catarrhini and Murinae, were derived from retropositions of OFD1X after the divergence of primates and rodents; and c) the presence of OFD1Y in the ampliconic region of the primate Y chromosome is an indication that the expansion of the ampliconic region may initiate from the X-degenerated sequence. In addition, we found that different regions of OFD1/OFD1X/OFD1Y are under differential selection pressures. The C-terminal half of OFD1 is under relaxed selection with an elevated Ka/Ks ratio and clustered positively selected sites, whereas the N-terminal half is under stronger constraints. This study provides some insights into why the OFD1X gene causes OFD1 (male-lethal X-linked dominant) and SGBS2 & JSRDs (X-linked recessive) syndromes in humans, and reveals the origin and evolution of the OFD1 family, which will facilitate further clinical investigation of the OFD1-related syndromes