Ruvinsky Lab home page.

I am broadly interested in the evolution of development (Evo-Devo), evolutionary genomics and molecular evolution. The overarching goal of the lab is to integrate developmental, genomic and computational approaches to understand the evolution of genes and gene functions. Students and post-docs in the lab are encouraged to develop their own projects under the broad umbrella of these research interests. Currently we are pursuing two major projects:

1. The origin and diversification of the nervous system

The origin of multicellular animals was accompanied by an increase in the number of distinct cell types, chief among these being neurons. How and when did neurons arise in evolution? We are aiming to reconstruct the series of molecular events that led to their origin and subsequent diversification.

As a first step in this direction we asked the question What genes are expressed in all neurons, and no cells other than neurons? Such pan-neuronal genes comprise a molecular definition of basic neuronal features and thus provide a window into their origin. By using computational genomics we have discovered that many pan-neuronal genes in C. elegans share common motifs in their cis-regulatory elements, suggesting that their expression is controlled by a common set of transcription factors (Ruvinsky et al. 2005; unpublished). We are currently combining experimentation with computational analyses of the C. elegans and other animal genomes to identify sets of genes that characterize different neuronal subtypes and will use these to elucidate the evolution of the animal nervous systems.

2. Evolution of transcriptional gene regulation

The current view of developmental evolution posits that morphological differences between species are largely caused by changes in regulatory (as opposed to coding) DNA sequences. Extensive studies have revealed some of the major forces that shape the observed patterns of protein evolution. In contrast, less is known about the evolution of cis-regulatory sequences. We are working to fill this gap.

It is well established that orthologous genes are expressed in similar patterns even between distantly related species. Coupled with a high degree of functional conservation of transcription factors, this would suggest that cis-regulatory elements have also been conserved over long periods of time. However, this does not appear to be the case when the cis-regulatory elements of Drosophila genes are tested in C. elegans (Ruvinsky and Ruvkun 2003). Promoter swaps between closely related species of nematodes show that even over much shorter phylogenetic distances there is a noticeable amount of functional divergence.

A possible explanation for this paradox could be that promoters co-evolve with their cognate transcription factors, and that this results in the conservation of gene expression patterns despite rapid sequence turnover. To test predictions of this hypothesis we are currently investigating the pattern and functional consequences of cis- and trans-regulatory evolution.

Recent Publications

Ruvinsky I., Ohler U., Burge C. B. and Ruvkun G. (2005).

Computational and experimental analyses of pan-neuronal genes in C. elegans. In review

Ruvinsky I. and Ruvkun G. (2003).

Functional tests of enhancer conservation between distantly related species. Development 130: 5133-5142.

Ruvinsky I. and Gibson-Brown J. J. (2000).

Genetic and developmental bases of serial homology in vertebrate limb evolution. Development 127: 5233-5244.

Ruvinsky I., Oates A. C., Silver L. M. and Ho R. K. (2000).

The evolution of paired appendages in vertebrates: T-box genes in the zebrafish. Dev. Genes Evol. 210: 82-91.

Ruvinsky I., Silver L. M. and Gibson-Brown J. J. (2000).

Phylogenetic analysis of T-box genes demonstrates the importance of amphioxus for understanding evolution of the vertebrate genome. Genetics 156: 1249-1257.

Ruvinsky I., Silver L. M. and Ho R. K. (1998).

Characterization of the zebrafish tbx16 gene and evolution of the vertebrate T-box family. Dev. Genes Evol. 208: 94-99.

Ruvinsky I. and Silver L. M. (1997).

Newly identified paralogous groups on mouse chromosomes 5 and 11 reveal the age of a T-box cluster duplication. Genomics 40: 262-266.

Ruvinsky I. and Maxson L. R. (1996).

Phylogenetic relationships among bufonoid frogs (Anura: Neobatrachia) inferred from mitochondrial DNA sequences. Mol. Phylogenet. Evol. 5: 533-547.