Genome Biology - Latest Articles
The latest research articles published by Genome Biology

Nuclear transcription factors in mammalian mitochondria
28 Jul 2010 at 6:00pm
Nuclear transcription factors have been detected in mammalian mitochondria and may directly regulate mitochondrial gene expression. Emerging genomics techniques may overcome outstanding challenges in this field.
Paternally biased X inactivation in mouse neonatal brain
by Xu WangPaul SolowayAndrew Clark
26 Jul 2010 at 6:00pm
Background: X-inactivation in female eutherian mammals has long been considered to occur at random in embryonic and postnatal tissues. Methods for scoring allele-specific differential expression with a high degree of accuracy have recently motivated a quantitative reassessment of the randomness of X inactivation. Results: After RNA-seq data revealed what appeared to be a chromosome-wide bias toward under-expression of paternal alleles in mouse tissue, we applied pyrosequencing to mouse brain cDNA samples from reciprocal cross F1 progeny of divergent strains and found a small but consistent and highly statistically significant excess tendency to under-express the paternal X chromosome. Conclusions: The bias toward paternal X inactivation is reminiscent of marsupials (and extraembryonic tissues in eutherians), suggesting that there may be retained an evolutionarily conserved epigenetic mark driving the bias. Allelic bias in expression is also influenced by the sampling effect of X inactivation and by cis-acting regulatory variation (eQTL), and for each gene we quantify the contributions of these effects in two different mouse strain combinations while controlling for variability in Xce alleles. In addition, we propose an efficient method to identify and confirm genes that escape X inactivation in normal mice by directly comparing the allele-specific expression ratio profile of multiple X-linked genes in multiple individuals.
Genomic information infrastructure after the deluge
25 Jul 2010 at 6:00pm
Maintaining up-to-date annotation on reference genomes is becoming more important, not less, as the ability to rapidly and cheaply resequence genomes expands.
Evolutionary divergence in the fungal response to fluconazole revealed by sof...
by Dwight KuoKai TanGuy ZinmanTimothy RavasiZiv Bar-JosephTrey Ideker
22 Jul 2010 at 6:00pm
Background: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.
Annotating conserved and novel features of primate transcriptomes using seque...
22 Jul 2010 at 6:00pm
Recent high-throughput sequencing of chimpanzee brain and liver transcriptomes published in Genome Biology reveals multiple transcripts lost in the human genome and highlights the incompleteness of primate genome annotations.See research article: http://genomebiology.com/2010/11/7/R78
Identification of novel exons and transcribed regions by chimpanzee transcrip...
by Anna WetterbomAdam AmeurLars FeukUlf GyllenstenLucia Cavelier
22 Jul 2010 at 6:00pm
Background: We profile the chimpanzee transcriptome by using deep sequencing of cDNA from brain and liver, aiming to quantify expression of known genes and to identify novel transcribed regions. Results: Using stringent criteria for transcription, we identify 12,843 expressed genes, with a majority being found in both tissues. We further identify 9,826 novel transcribed regions that are not overlapping with annotated exons, mRNAs or ESTs. Over 80% of the novel transcribed regions map within or in the vicinity of known genes, and by combining sequencing data with de novo splice predictions we predict several of the novel transcribed regions to be new exons or 3' UTRs. For approximately 350 novel transcribed regions, the corresponding DNA sequence is absent in the human reference genome. The presence of novel transcribed regions in five genes and in one intergenic region is further validated with RT-PCR. Finally, we describe and experimentally validate a putative novel multi-exon gene that belongs to the ATP-cassette transporter gene family. This gene does not appear to be functional in human since one exon is absent from the human genome. In addition to novel exons and UTRs, novel transcribed regions may also stem from different types of noncoding transcripts. We note that expressed repeats and introns from unspliced mRNAs are especially common in our data. Conclusions: Our results extend the chimpanzee gene catalogue with a large number of novel exons and 3' UTRs and thus support the view that mammalian gene annotations are not yet complete.
Analysis of the copy number profiles of several tumor samples from the same p...
by Eric LetouzeYves AlloryMarc BolletFrancois RadvanyiFrederic Guyon
21 Jul 2010 at 6:00pm
We present a computational method, TuMult, for reconstructing the sequence of copy number changes driving carcinogenesis, based on the analysis of several tumor samples from the same patient. We demonstrate the reliability of the method with simulated data, and describe applications to three different cancers, showing that TuMult is a valuable tool for the establishment of clonal relationships between tumor samples and the identification of chromosome aberrations occurring at crucial steps in cancer progression.
RNA Polymerase mapping during stress responses reveals widespread nonproducti...
by Tae Soo KimChih Long LiuMoran YassourJohn HolikNir FriedmanStephen BuratowskiOliver Rando
15 Jul 2010 at 6:00pm
Background: The use of genome-wide RNA abundance profiling by microarrays and deep sequencing has spurred a revolution in our understanding of transcriptional control. However, changes in mRNA abundance reflect the combined effect of changes in RNA production, processing, and degradation, and thus, mRNA levels provide an occluded view of transcriptional regulation. Results: To partially disentangle these issues, we carry out genome-wide RNA Polymerase II (PolII) localization profiling in budding yeast in two different stress response time courses. While mRNA changes largely reflect changes in transcription, there remains a great deal of variation in mRNA levels that is not accounted for by changes in PolII abundance. We find that genes exhibiting excess mRNA produced per PolII are enriched for those with overlapping cryptic transcripts, indicating a pervasive role for nonproductive or regulatory transcription in control of gene expression. Finally, we characterize changes in PolII localization when PolII is genetically inactivated using the rpb1-1 temperature-sensitive mutation. We find that PolII is lost from chromatin after roughly an hour at the restrictive temperature, and that there is a great deal of variability in the rate of PolII loss at different loci. Conclusions: Together, these results provide a global perspective on the relationship between PolII and mRNA production in budding yeast.
Quantifying the mechanisms of domain gain in animal proteins
by Marija BuljanAdam FrankishAlex Bateman
14 Jul 2010 at 6:00pm
Background: Protein domains are protein regions that are shared among different proteins and are frequently functionally and structurally independent from the rest of the protein. Novel domain combinations have a major role in evolutionary innovation. However, the relative contributions of the different molecular mechanisms that underlie domain gains in animals are still unknown. By using animal gene phylogenies we were able to identify a set of high confidence domain gain events and by looking at their coding DNA investigate the causative mechanisms. Results: Here we show that the major mechanism for gains of new domains in metazoan proteins is likely to be gene fusion through joining of exons from adjacent genes, possibly mediated by non-allelic homologous recombination. Retroposition and insertion of exons into ancestral introns through intronic recombination are, in contrast to previous expectations, only minor contributors to domain gains and have accounted for less than 1% and 10% of high confidence domain gain events, respectively. Additionally, exonisation of previously non-coding regions appears to be an important mechanism for addition of disordered segments to proteins. We observe that gene duplication has preceded domain gain in at least 80% of the gain events. Conclusions: The interplay of gene duplication and domain gain demonstrates an important mechanism for fast neofunctionalisation of genes.
How do proteins gain new domains?
14 Jul 2010 at 6:00pm
A study of the contributions of different mechanisms of domain gain in animal proteins suggests that gene fusion is likely to be most frequent.

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