Erives Lab
EcoEvoDevo
"However clever you
think cells are:
They are clever!"
of the 40th anniversary of his
Positional Information model
in a special session on
morphogen gradients.
Gordon Research Conference:
Developmental Biology
Andover, New Hampshire
June 24th, 2009
Albert J. Erives
Dept. of Biological Sciences
Dartmouth College
Our lab works on the biology of regulatory DNAs, including their structure, function, and genomic evolution. In particular we are investigating how evolution encodes specific gene induction events in regulatory DNAs. We typically seek to ask these questions in interesting phylogenetic or ecological contexts (eco-evo-devo).
RECENT AND ONGOING PROJECTS:
Evolution of readouts of the Dorsal morphogen gradient system of Drosophila
Morphogen gradients provide important long-range patterning mechanisms to developing organisms. Specifically, morphogen gradients allow different genes to respond to specific levels of a morphogen, and thereby allow the cell to infer its position in the multi-cellular body. In order to better understand how this is accomplished, we have been studying a set of transcriptional enhancers across the genome that mediate read-outs over a wide-range of concentration thresholds for nuclear Dorsal, which patterns the dorsal/ventral axis of the fly embryo. These particular developmental enhancers share a characteristic arrangement of specialized binding sites for Dorsal, Twist, Snail, and CSL. We have experimented with multiple enhancers from different dipteran species that have evolved to undergo embryogenesis in different environmental niches. So far, every enhancer that we have identified and assayed is sensitive to a specific threshold concentration level of the Dorsal morphogen. Furthermore, enhancers (cis-regulatory DNAs) from a lineage co-evolve as a group to common changes in trans, which is a process that has characterized each lineage. Our work to date is characterizing how these changes are encoded in DNA sequences.Evolutionary origin of a Myc/Max growth switch for ribosome biogenesis
Comparative regulatory genomics provides a powerful approach for identifying the nature and evolutionary origins of cell signaling pathways. Using these techniques, we have been able to identify and document the evolutionary birth of a growth switch in the latest common ancestor of holozoans, which includes metazoans and choanoflagellates. Using new techniques in comparative regulatory genomics, we have shown that this holozoan ancestor evolved the Myc/Max transcription factors and their DNA binding sites in the core promoters of ribosome biogenesis (RiBi) genes, whose products function in the nucleolus. We also show that Myc/Max alone, but neither Mad/Max nor Mnt/Max, is responsible for evolutionary maintenance of the Myc/Max binding site at the core promoters of RiBi genes. Myc is often amplified in growing human cancers, and often is downstream of RTK-mediated growth signaling, components of which also appear in choanoflagellates. Interestingly, we have also demonstrated that nematodes, which are small-bodied metazoans, have secondarily lost both Myc and its downstream DNA binding sites sites in RiBi core promoters. We propose that this is a direct consequence of a body plan composed of 1000 somatic cells and the deprecated need for the high rates of protein synthesis associated with rapidly expanding cell populations.
Last modified Feb. 2nd, 2010.
