p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy

New paper from Eran Segals' lab.

The Importance of Being Cis: Evolution of Orthologous Fish and Mammalian Enhancer Activity

Deborah I. Ritter1, Qiang Li, Dennis Kostka, Katherine S. Pollard, Su Guo,
Jeffrey H. Chuang

• "Identified 41 zebrafish mutual best BLAST hits to orthologous enhancer sequences in the human genome. Zebrafish sequences were tested for enhancer activity in a Tol2 transposon GFP assay; human sequences had been assayed for enhancer activity in mouse embryos."
• "A minority of the enhancer pairs showed conserved anatomical activity (13/41, 31.7%)."
• "Correspondence between CNE activity patterns and target gene expression was irregular, with 14 zebrafish CNEs driving expression at least partially overlapping the expression of the predicted target gene."
• "Sequence Conservation is a Weak Predictor of Conserved Enhancer Activity. By calculating the true positive rate and false positive rate at each threshold of sequence conservation, we computed a receiver operating characteristic (ROC) curve (Figure 3A2). The area under the curve is 0.684, indicating a small improvement over random guessing."
• "an enhancer with accelerated primate evolution has been shown to have lineage-specific human activity"
• "We found that mammalian PAB has similar discriminative power as human-zebrafish
  sequence percent identity"
• "we compared the ZZ, HZ, and HM activity patterns simultaneously. In 4/13 (31%) of the cases, all three experiments drive similar anatomical expression in homologous tissues. This is a higher fraction than expected if cis- and trans- evolution were independent ((1- 0.39) × (1-0.69) = 19%), suggesting concerted cis- and trans- evolution to maintain function in each species. In other words, positive selection has likely acted on ~10% of our tested enhancer sequences to optimize them for species-specific trans- regulatory factors."
  

A Widespread Chromosomal Inversion Polymorphism Contributes to a Major Life-History Transition, Local Adaptation, and Reproductive Isolation

An interesting new paper over at PLoS Bio today, looking at the role of chromosomal inversions in adaptation and speciation. In this study, the group found a chromosomal inversion polymorphism that is geographically widespread. Replicated crosses between the prezygotically reproductively isolated annual and perennial "ecotypes" of the yellow monkeyflower, Mimulus guttatus, revealed that chromosomal inversion arrangements are associated with patterns divergence across North America. The inversion polymorphism affected flowering time and other morphological traits between four pairs of annual and perennial populations. To determine if the inversion contributes to adaptation and reproductive isolation a reciprocal transplant experiment, where alternative arrangements of the inversion were reciprocally introgressed into the genetic backgrounds of each ecotype, were performed."Our results demonstrate for the first time in nature the contribution of an inversion to adaptation, an annual/perennial life-history shift, and multiple reproductive isolating barriers."

Evolution under Fluctuating Environments Explains Observed Robustness in Metabolic Networks

This article addresses the hypothesis, specific to metabolic networks, that robustness emerges as a byproduct of selection for biomass production in different environments. Evolutionary simulations of metabolic networks under stable and fluctuating environments demonstrated that networks evolved under the fluctuating environments can better tolerate deletions. Robustness was characterized by an increased number of independent fluxes and multifunctional enzymes in the evolved networks. When simulated evolution of these networks under a stable environment, any robustness they had acquired was lost. "These findings provide evidence that evolution under fluctuating environments can account for the observed robustness in metabolic networks."

It would be interesting to look at robustness in species that have evolved in particular enviorments, ie temperate vs tropic...

ChIP-Seq identification of weakly conserved hear enhancers (Blow et. al 2010)

1. ChIP-seq on P300 (a transcriptional coactivator)
2. Identified over 3000 genomic regions enriched for P300 binding in heart tissue (E11.5)
   
3. 84% of the peaks do not overlap p300 peaks found in any of the other tissues tested
   
4. 130 of the putative heart enhancers tested in vivo, 97 (75%) functioned as tissue-specific enhancers
   
5. “Notably, we found no significant difference in the frequency of positive heart enhancers among the highly conserved sequences (19/31, or 61%) compared with the sequences that overlapped no conservation (16/30, or 53%; P > 0.1 according to Fisher’s exact test). These results suggest that p300 is an accurate predictor of enhancer activity independent of sequence conservation, and they confirm the in vivo activity of weakly and apparently non-constrained heart enhancers”
6. “Notably, the enhancers identified in these studies exhibited highly restricted expression patterns, with 51/81 (63%) of enhancers driving reproducible reporter gene expression exclusively in the developing heart”
7. Overall, only 6% of candidate heart enhancer overlapped genome regions that were under extremely high constraint

This paper highlights that sequence conservation alone cannot be used as a sole indicator of functionality. Conservation-based methods severely underestimate the number of cis-regulatory elements. Furthermore, from an evolutionary standpoint, lineage specific enhancers (particularly those undergoing positive selection) are where the adaptive action may be taking place!

Another interesting point is the concept of tissue-specific patterns of evolution. This is a concept that has been knocking around for quite some time and is now gaining traction through experimental evidence (Wang 2007, Blekhman 2008).