Survival strategies for choosing the right postdoc position.

You are completing your PhD (at last!), and might be asking yourself, 'What do I have to accomplish as a postdoc if I want to get a faculty job at one of the top 25% of research universities?' This article is a follow up to last year's essay on picking a graduate studentship, and here I lay out the advice I give to young scientists who have determined that they want to make the next step towards a research faculty post

Comparative Genomics: One for all.

Using a common analysis pipeline to compare data from three major lineages of complex eukaryotes reveals that transcription seems to evolve at a common rate

Unwinding Limb Development.

The molecular mechanisms underpinning vertebrate body plan evolution are beginning to be unravelled. In this issue of Cell, Kvon et al. spectacularly demonstrate how transplanting snake-specific genetic changes found uniquely in serpent enhancers leads to limb loss in mice

Generalizing complexity: a fruitful partnership of functional genomics and systems biology.

A report on the meeting 'Functional Genomics and Systems Biology 2011', Wellcome Trust Conference Centre, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK, 29 November to 1 December, 2011

Nuclear transcription factors in mammalian mitochondria

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

Mitochondrial heteroplasmy in vertebrates using ChIP-sequencing data.

BACKGROUND: Mitochondrial heteroplasmy, the presence of more than one mitochondrial DNA (mtDNA) variant in a cell or individual, is not as uncommon as previously thought. It is mostly due to the high mutation rate of the mtDNA and limited repair mechanisms present in the mitochondrion. Motivated by mitochondrial diseases, much focus has been placed into studying this phenomenon in human samples and in medical contexts. To place these results in an evolutionary context and to explore general principles of heteroplasmy, we describe an integrated cross-species evaluation of heteroplasmy in mammals that exploits previously reported NGS data. Focusing on ChIP-seq experiments, we developed a novel approach to detect heteroplasmy from the concomitant mitochondrial DNA fraction sequenced in these experiments. RESULTS: We first demonstrate that the sequencing coverage of mtDNA in ChIP-seq experiments is sufficient for heteroplasmy detection. We then describe a novel detection method for accurate detection of heteroplasmies, which also accounts for the error rate of NGS technology. Applying this method to 79 individuals from 16 species resulted in 107 heteroplasmic positions present in a total of 45 individuals. Further analysis revealed that the majority of detected heteroplasmies occur in intergenic regions. CONCLUSION: In addition to documenting the prevalence of mtDNA in ChIP-seq data, the results of our mitochondrial heteroplasmy detection method suggest that mitochondrial heteroplasmies identified across vertebrates share similar characteristics as found for human heteroplasmies. Although largely consistent with previous studies in individual vertebrates, our integrated cross-species analysis provides valuable insights into the evolutionary dynamics of mitochondrial heteroplasmy

Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression.

To gain insight into how mammalian gene expression is controlled by rapidly evolving regulatory elements, we jointly analysed promoter and enhancer activity with downstream transcription levels in liver samples from 15 species. Genes associated with complex regulatory landscapes generally exhibit high expression levels that remain evolutionarily stable. While the number of regulatory elements is the key driver of transcriptional output and resilience, regulatory conservation matters: elements active across mammals most effectively stabilize gene expression. In contrast, recently evolved enhancers typically contribute weakly, consistent with their high evolutionary plasticity. These effects are observed across the entire mammalian clade and are robust to potential confounders, such as the gene expression level. Using liver as a representative somatic tissue, our results illuminate how the evolutionary stability of gene expression is profoundly entwined with both the number and conservation of surrounding promoters and enhancers

Variations in DNA Charge Transport with Nucleotide Composition and Sequence

Long-range oxidative damage to DNA has been demonstrated in experiments using a variety of remotely bound oxidants. However, the mechanism(s) by which charge is transported through the base pair stack needs still to be established. Recent theoretical proposals bring together tunneling and hopping mechanisms to describe charge transport. On the basis of measurements of damage yield, it has been proposed that charge transport occurs by hopping between guanine sites and tunneling through TA steps. In accord with guanine hopping, oxidative damage over long distances was not observed when 5‘-TATATA-3‘ intervened between G sites. Phonon-assisted polaron hopping has been suggested as an alternative mechanism. In this model, the sequence-dependent conformational dynamics of DNA are expected to aid in charge transport