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Molecular population genetics and evolution (Drosophila and Arabidopsis)


Egg size variation


Drosophila Transcriptional Enhancers Evolution

Transcription factor binding sites (TFBS) turnover (i.e. lineage specific gain and loss) is a well-documented phenomenon in eukaryote cis-regulatory modules (CRM). The wide spread of the phenomenon and the appearance of conserved expression patterns for diverged orthologous CRM led to the standing view that the observed gain and loss of TFBS were functionally and selectively neutral. To the contrary, genome-wide population genetics analyses have unequivocally identified signatures of positive selection acting in noncoding regions in general, and particularly in 5' and 3' untranscribed regions of genes. To specifically test the neutral vs. selection hypotheses for the TFBS turnover process, we analyzed natural variation patterns within and between two closely related Drosophila species in a set of experimentally defined and validated TFBS dataset ( We found the patterns of divergence and polymorphism for two types of mutations -- those inferred to increase or decrease the binding affinity respectively-- are not compatible with a neutral hypothesis. Instead, multiple lines of evidence suggested that positive selection have contributed to gain as well as loss of TFBS in the two lineages, with purifying selection maintaining existing TFBS in the population. Spacer sequences also showed signatures of negative and positive selection. Based on these results, we propose that CRM function may experience constant pressures to adapt to both external environmental changes as well as internal genetic network alterations. In the mean time, however, the high connectivity in the regulatory network implies pleiotropic effects while the essentiality of genes controlled by the network may call for accurate regulation, both suggesting that the net change in CRM function will be highly constrained, which would explain why distantly related species with their CRM sequences diverged beyond recognition could still drive highly similar expression patterns in a transgenic reporter assay. In the future, we are interested in elucidating the functional consequences of TFBS turnover and the relevant co-evolution in the trans or other cis components to better understand how gene regulation evolves and how they contribute to species divergence and/or phenotypic evolution.

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