We are broadly interested in the evolution of development (Evo-Devo), evolution of gene regulation, evolutionary genomics, molecular evolution, and organismal biology. We integrate a variety of experimental and computational approaches to investigate these problems. Please explore the projects pursued by individual members of the lab. You are welcome to contact us if you are interested in joining the lab or have any questions.
A paper by Antoine and Ilya was published in PLoS Genetics. We systematically tested functional conservation of orthologous cis-regulatory elements between C. elegans and closely related species C. briggsae, C. remanei, C. brenneri, and C. japonica. Most exogenous cis elements directed expression in the same cells as their C. elegans orthologs, confirming gross conservation of regulatory mechanisms. However, the majority also drove expression in cells outside endogenous patterns, suggesting functional divergence. When placed in C. elegans, a given non-elegans cis element was far more likely to be expressed in this kind of ectopic pattern than to have lost the ability to be expressed in the endogenous pattern. Recurrent ectopic expression of different promoters in the same C. elegans cells may reflect biases in the directions in which expression patterns can evolve due to shared regulatory logic of coexpressed genes. Because several patterns repeatedly emerged from our survey, we are encouraged to think that general rules governing regulatory evolution may exist and be discoverable. See the paper for more details.
Antoine Barrière left the lab to take up a CNRS position at Institut de Biologie du Developpement de Marseille. Bonne chance, Antoine!
We welcomed Kat Beilsmith to the lab.
Aime Agather left the lab to start graduate studies at the University of Wisconsin. Good luck, Aime!
Catherine Sodroski successfully defended her Honors Thesis and left to pursue a year of research at the NIH before applying to graduate school.
Kelsei Eichel, our lab alum, was awarded an NSF Graduate Fellowship. Congratulations, Kelsie!
Paul Wang left the lab to join SA Pathology in Australia. Good luck, Paul!
A paper by Antoine, Kacy, and Ilya was published in PLoS Genetics. The unc-47 promoters of C. elegans and C. briggsae drive indistinguishable expression patterns, but when the promoters are swapped between species, differences in expression can be observed. These differences show evidence of cis-trans coevolution. The C. briggsae promoter derives its unique regulatory properties from epistatic interactions within the promoter and between the promoter and trans-acting regulators. The cis-regulatory element experienced rapid sequence evolution in the C. briggsae lineage. Despite evolution that changes promoter function at the molecular level, the promoter's biological function--to drive expression in all and only 26 GABAergic neurons--remains unchanged. Our findings therefore additionally suggest that evolutionary novelty should not be inferred on the basis of accelerated sequence alone. See the paper for more details.
A paper by Paul and Ilya was published in Genome Biology and Evolution. We investigated the evolution of small RNA genes in Caenorhabditis nematodes. We found that snRNA and tRNA genes form large families, which have persisted since before the common ancestor of Metazoa. Yet, individual genes die relatively rapidly, with few orthologs having survived since the divergence of Caenorhabditis elegans and Caenorhabditis briggsae. In contrast, genes encoding snoRNAs are either single-copy or form small families. Individual snoRNAs turn over at a relatively slow rate, such that most C. elegans genes have clearly identifiable orthologs in C. briggsae. Similarly, in Drosophila, genes from larger snRNA families die at a faster rate than their counterparts from single-gene families. Our results suggest that a relationship between family size and the rate of gene turnover may be a general feature of genome evolution. See the paper for more details.
A paper by Erin, Ilya, and our collaborators from Northwestern University was published in PLoS Computational Biology. We have developed a simple, macro-level model to describe how chronic temperature stress affects reproduction in C. elegans. Our approach uses fundamental engineering principles and provides quantitatively accurate predictions of performance under a range of physiologically relevant conditions. We find considerable heterogeneity in responses of individual animals to heat stress, which can be understood as modulation of a few processes and may represent a strategy for coping with the ever-changing environment. Our results suggest, surprisingly, that the behavior of complex biological systems may be determined by a small number of key components. See the paper for more details.
A paper by Kacy and Ilya was published in PLoS Genetics. We synthesize the results of 230 experiments performed on insects and nematodes in which regulatory DNA from one species was used to drive gene expression in another species. General principles of regulatory evolution emerge. Gene regulatory evolution is widespread and accumulates with genetic divergence in both insects and nematodes. Divergence in cis is more common than divergence in trans. Coevolution between cis and trans shows a particular increase over greater evolutionary timespans, especially in sex-specific gene regulation. Despite these generalities, the evolution of gene regulation is gene- and taxon-specific. The congruence of these conclusions with evidence from other types of experiments suggests that general principles are discoverable, and a unified view of the tempo and mode of regulatory evolution may be achievable. See the paper for more details.
A paper by Rob Arthur and Ilya was published in Genetics. We tested whether functionally important sites in bacterial, yeast, and animal promoters are more conserved than their neighbors. We found that substitutions are predominantly seen in less important sites and that those that occurred tended to have less impact on gene expression than possible alternatives. These results suggest that purifying selection operates on promoter sequences. See the paper for more details.
A project carried out by Zhengying and Kelsie was published in PLoS ONE. We demonstrated that cis-regulatory elements of fly and human heat-shock genes are upregulated in C. elegans upon exposure to heat. Because enhancers of tissue-specific Drosophila genes are not appropriately recognized in nematodes, our results suggest that different aspects of regulatory logic may evolve at different rates. See the paper for more details.
A project carried out by Antoine and Kacy was published in PLoS Genetics. We demonstrated that promoter of C. elegans unc-47 consists of two distinct domains. The proximal is conserved and sufficient to direct appropriate spatial expression. The distal is not conserved, but confers robustness of expression, arguing that this function does not require sequence conservation. Robustness-promoting sequences are AT-enriched consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter. See the paper for more details.
We welcomed Kelsie Eichel to the lab.
Congratulations to Kacy Gordon who was awarded an NSF Graduate Research Fellowship!
Our paper reporting a new method for predicting a class of small non-protein-coding RNAs (H/ACA snoRNAs) was published in RNA. Short RNAs are notoriously difficult to discover using genome sequences alone. We developed an algorithm that relies on empirically discovered sequences motifs and the notions of "genome neighborhoods" where snoRNAs genes are most likely to be found. We showed that by combining diverse data types into a single prediction engine and by entraining it on features restricted to particular phylogenetic groups, we can substantially improve the quality of computational predictions. See the paper for more details.
We welcomed Erin Zucker Aprison to the lab.
We welcomed two people in the lab − Zhengying He (a new postdoc) and Kacy Gordon (a graduate student).
Our study on "Detecting heterozygosity in shotgun genome assemblies" was published in Genome Research. We demonstrated that despite intense inbreeding, the heterozygous fraction of the whole genome shotgun assemblies of three gonochoristic Caenorhabditis species, C. brenneri, C. remanei, and C. japonica, is considerable (up to 30%). We developed approaches for recognizing heterozygous regions of genome assemblies. Because of this extensive retained heterozygosity, allele frequencies within sequenced "strains" are continuing to change, and phenotypes are continuing to evolve. See the paper for more details.
(c) The University of Chicago, 2009. Designed and maintained by Paul Wang