Evolutionary Biology for the 21st Century

Evolutionary Biology for the 21st Century:
by Jonathan B. Losos, Stevan J. Arnold, Gill Bejerano, E. D. Brodie, David Hibbett, Hopi E. Hoekstra, David P. Mindell, Antónia Monteiro, Craig Moritz, H. Allen Orr, Dmitri A. Petrov, Susanne S. Renner, Robert E. Ricklefs, Pamela S. Soltis, Thomas L. Turner

Transcriptional repressors: multifaceted regulators of gene expression [REVIEW]

Transcriptional repressors: multifaceted regulators of gene expression [REVIEW]: Nicola Reynolds, Aoife O'Shaughnessy, and Brian Hendrich


Through decades of research it has been established that some chromatin-modifying proteins can repress transcription, and thus are generally termed ‘repressors’. Although classic repressors undoubtedly silence transcription, genome-wide studies have shown that many repressors are associated with actively transcribed loci and that this is a widespread phenomenon. Here, we review the evidence for the presence of repressors at actively transcribed regions and assess what roles they might be playing. We propose that the modulation of expression levels by chromatin-modifying, co-repressor complexes provides transcriptional fine-tuning that drives development.

Establishing and maintaining gene expression patterns: insights from sensory receptor patterning [PRIMER]

Establishing and maintaining gene expression patterns: insights from sensory receptor patterning [PRIMER]: Jens Rister, Claude Desplan, and Daniel Vasiliauskas


In visual and olfactory sensory systems with high discriminatory power, each sensory neuron typically expresses one, or very few, sensory receptor genes, excluding all others. Recent studies have provided insights into the mechanisms that generate and maintain sensory receptor expression patterns. Here, we review how this is achieved in the fly retina and compare it with the mechanisms controlling sensory receptor expression patterns in the mouse retina and in the mouse and fly olfactory systems.

Number of Nuclear Divisions in the Drosophila Blastoderm Controlled by Onset of Zygotic Transcription

Number of Nuclear Divisions in the Drosophila Blastoderm Controlled by Onset of Zygotic Transcription: Hung-wei Sung, Saskia Spangenberg, Nina Vogt, Jörg Großhans. The cell number of the early Drosophila embryo is determined by exactly 13 rounds of synchronous nuclear divisions, allowing cellularization and formation of the embryonic epithelium [1]. T....

The Underlying Molecular and Network Level Mechanisms in the Evolution of Robustness in Gene Regulatory Networks

The Underlying Molecular and Network Level Mechanisms in the Evolution of Robustness in Gene Regulatory Networks:
by Mario Pujato, Thomas MacCarthy, Andras Fiser, Aviv Bergman

Gene regulatory networks show robustness to perturbations. Previous works identified robustness as an emergent property of gene network evolution but the underlying molecular mechanisms are poorly understood. We used a multi-tier modeling approach that integrates molecular sequence and structure information with network architecture and population dynamics. Structural models of transcription factor-DNA complexes are used to estimate relative binding specificities. In this model, mutations in the DNA cause changes on two levels: (a) at the sequence level in individual binding sites (modulating binding specificity), and (b) at the network level (creating and destroying binding sites). We used this model to dissect the underlying mechanisms responsible for the evolution of robustness in gene regulatory networks. Results suggest that in sparse architectures (represented by short promoters), a mixture of local-sequence and network-architecture level changes are exploited. At the local-sequence level, robustness evolves by decreasing the probabilities of both the destruction of existent and generation of new binding sites. Meanwhile, in highly interconnected architectures (represented by long promoters), robustness evolves almost entirely via network level changes, deleting and creating binding sites that modify the network architecture.

A second-generation assembly of the Drosophila simulans genome provides new insights into patterns of lineage-specific divergence [RESEARCH]

A second-generation assembly of the Drosophila simulans genome provides new insights into patterns of lineage-specific divergence [RESEARCH]:
We create a new assembly of the Drosophila simulans genome using 142 million paired short-read sequences and previously published data for strain w⁵⁰¹. Our assembly represents a higher-quality genomic sequence with greater coverage, fewer misassemblies, and, by several indexes, fewer sequence errors. Evolutionary analysis of this genome reference sequence reveals interesting patterns of lineage-specific divergence that are different from those previously reported. Specifically, we find that Drosophila melanogaster evolves faster than D. simulans at all annotated classes of sites, including putatively neutrally evolving sites found in minimal introns. While this may be partly explained by a higher mutation rate in D. melanogaster, we also find significant heterogeneity in rates of evolution across classes of sites, consistent with historical differences in the effective population size for the two species. Also contrary to previous findings, we find that the X chromosome is evolving significantly faster than autosomes for nonsynonymous and most noncoding DNA sites and significantly slower for synonymous sites. The absence of a X/A difference for putatively neutral sites and the robustness of the pattern to Gene Ontology and sex-biased expression suggest that partly recessive beneficial mutations may comprise a substantial fraction of noncoding DNA divergence observed between species. Our results have more general implications for the interpretation of evolutionary analyses of genomes of different quality.

GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility [RESEARCH]

GATA3 acts upstream of FOXA1 in mediating ESR1 binding by shaping enhancer accessibility [RESEARCH]:
Estrogen receptor (ESR1) drives growth in the majority of human breast cancers by binding to regulatory elements and inducing transcription events that promote tumor growth. Differences in enhancer occupancy by ESR1 contribute to the diverse expression profiles and clinical outcome observed in breast cancer patients. GATA3 is an ESR1-cooperating transcription factor mutated in breast tumors; however, its genomic properties are not fully defined. In order to investigate the composition of enhancers involved in estrogen-induced transcription and the potential role of GATA3, we performed extensive ChIP-sequencing in unstimulated breast cancer cells and following estrogen treatment. We find that GATA3 is pivotal in mediating enhancer accessibility at regulatory regions involved in ESR1-mediated transcription. GATA3 silencing resulted in a global redistribution of cofactors and active histone marks prior to estrogen stimulation. These global genomic changes altered the ESR1-binding profile that subsequently occurred following estrogen, with events exhibiting both loss and gain in binding affinity, implying a GATA3-mediated redistribution of ESR1 binding. The GATA3-mediated redistributed ESR1 profile correlated with changes in gene expression, suggestive of its functionality. Chromatin loops at the TFF locus involving ESR1-bound enhancers occurred independently of ESR1 when GATA3 was silenced, indicating that GATA3, when present on the chromatin, may serve as a licensing factor for estrogen–ESR1-mediated interactions between cis-regulatory elements. Together, these experiments suggest that GATA3 directly impacts ESR1 enhancer accessibility, and may potentially explain the contribution of mutant-GATA3 in the heterogeneity of ESR1+ breast cancer.