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Stern Lab

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Current Research
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This is an extraordinary time to study evolutionary biology. The answers to many deep and old questions in evolution are being unraveled with the aid of new technologies. Rapid genome sequencing is only the beginning, providing comparative maps of the underlying instructions for organismal form, physiology and behavior; new methods for probing gene function and cell biology provide the complementary tools. We exploit these tools and develop new tools to ask how molecules have evolved to generate morphological and behavioral novelty in evolution.

 

We believe that the answers to these questions will provide a revised view of how evolutionary change happens in natural populations.

 

We seek more than a comparative understanding of these questions. We want to know, precisely, how do molecular changes ramify through cell biology to generate phenotypic evolution. 

 

We focus on a group of closely related species in the Drosophila melanogaster species group. These species display enormous morphological, physiological, behavioral and ecological diversity. And, many of these species can be intercrossed and most of the crossable species pairs share gene synteny on all chromosomes.  This rather unusual set of evolutionary circumstances -- combined with the close evolutionary relatedness of these species to the model species D. melanogaster -- provides a rare opportunity to  identify the genetic causes of phenotypic evolution and to probe the functional consequences of these molecular changes.

 

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Research Foci

We study a range of biological problems because lab members are provided with extraordinary independence to pursue their passions. Here are a few of the problems we are currently pursuing

Evolution of Behavior

We aim to identify the genetic and neural basis for the evolution of behavior, because we believe that there may be general principles to behavior evolution, similar to the principles that have been revealed for morphological evolution (Stern & Orgogozo, 2009; Stern 2010). 

Current projects include genetic studies of the causes of variation in courtship song and wing rowing behavior. We have developed several tools to aid these studies, including high-throughput genotyping (Andolfatto et al. 2011) and phenotyping platforms (Arthur et al. 2013) and new transgenic reagents for all of the species we study. 

We are also pursuing neuroanatomical approaches to identify the neural circuits that govern the production of courtship song (Shirangi et al. 2013) and other courtship-related behaviors. Ultimately, we hope to identify changes in neural circuits that caused the evolution of novel courtship behaviors.

Evolution of Morphology

For many years, the lab has studied the genetic causes for the evolution of a morphological difference between species, a change in the pattern of cuticular trichomes on larvae (Sucena & Stern 2000). In a series of papers, we have demonstrated that this seemingly trivial morphological difference resulted from the accumulation of a very large number of mutations of small effect all at a single gene, called shavenbaby (Sucena & Stern 2000, McGregor et al. 2007, Frankel et al. 2011). 

These results help to explain a confusing discrepancy between many observations in evolutionary genetics -- which indicate that evolution often occurs by the accumulation of mutations of small effect -- and the results from evolutionary developmental biology -- which suggest that morphological evolution often occurs by changes at key regulatory genes. In fact, both may be true. Long-term evolutionary changes may have resulted from the accumulation of small-effect mutations at a few, special loci. We call these hot-spot genes and we suspect that the structure of developmental networks helps to explain why mutations at these hot-spot genes are preferred over mutations elsewhere in the network (Stern & Orgogozo 2008, 2009).

If some genes really are hot spots for evolutionary change, then we would expect to see these genes involved in similar evolutionary changes in other lineages. We therefore examined species of the D. virilis clade of flies, which also display a diversity of larval trichome patterns. In this group, we found that the pattern of svb expression is precisely correlated with larval trichome patterns, suggesting that svb is indeed involved in the evolution of trichome patterns in this group of species as well (Sucena et al., 2003). Recently, we have demonstrated that not only has svb evolved in the D. virilis clade, but precisely the same cis-regulatory enhancers have evolved both in the D. virilis clade and in the D. melanogaster group to generate identical morphological evolution (Frankel et al. 2011). This is a remarkable case of genetic parallelism underlying morphological convergence.

We are now focused on identifying the specific transcription factors that bind to the evolving binding sites in these enhancers, in the hope that we will identify new principles of developmental evolution.

Mechanisms of Transcription

In recent years, we have developed a deeper interest in the mechanisms of gene transcription. We have developed new TAL-based tools that allow targeting of transcriptional activators and repressors anywhere in the genome in developing animals (Crocker & Stern 2013). We have been exploiting these powerful tools to test existing models of enhancer function.

In a second effort, in collaboration with Richard Mann's lab (Columbia Medical School), we have explored precisely how Hox proteins regulate native enhancers. Hox regulation has presented a long-standing paradox because all Hox proteins bind to similar DNA sequences with high affinity. How, then, do different Hox genes regulate different subsets of target genes to generate diversity along the anterior-posterior axis of animals? This is the so-called Hox specificity paradox. We have discovered that Hox proteins bind primarily to clusters of extremely low affinity sites to regulate enhancers. Hox proteins solve the specificity paradox by binding to clusters of sites of extremely low affinity (Crocker et al. 2015). 

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"I came to Janelia to do science with my own hands. I am an inveterate lab rat and I really appreciate the fact that I can spend all day, every day, doing experiments that enhance the lab's research. I feel incredibly lucky to be a post-doc in my own lab!"

David L. Stern, December 2014