Predicting Ancestral Segmentation Phenotypes from Drosophila to Anopheles Using In Silico Evolution

Jeremy B. Rothschild, Panagiotis Tsimiklis, Eric D. Siggia, Paul François, Claude Desplan
<span title="2016-05-26">2016</span> <i title="Public Library of Science (PLoS)"> <a target="_blank" rel="noopener" href="" style="color: black;">PLoS Genetics</a> </i> &nbsp;
Molecular evolution is an established technique for inferring gene homology but regulatory DNA turns over so rapidly that inference of ancestral networks is often impossible. In silico evolution is used to compute the most parsimonious path in regulatory space for anteriorposterior patterning linking two Dipterian species. The expression pattern of gap genes has evolved between Drosophila (fly) and Anopheles (mosquito), yet one of their targets, eve, has remained invariant. Our model predicts
more &raquo; ... at stripe 5 in fly disappears and a new posterior stripe is created in mosquito, thus eve stripe modules 3+7 and 4+6 in fly are homologous to 3+6 and 4+5 in mosquito. We can place Clogmia on this evolutionary pathway and it shares the mosquito homologies. To account for the evolution of the other pair-rule genes in the posterior we have to assume that the ancestral Dipterian utilized a dynamic method to phase those genes in relation to eve. Author Summary The last common ancestor of the fruit fly (Drosophila) and mosquito (Anopheles) lived more than 200 Million years ago. Can we use available data on insects alive today to infer what their ancestor looked like? In this manuscript, we focus on early embryonic development, when stripes of genetic expression appear and define the location of insect segments ("segmentation"). We use an evolutionary algorithm to reconstruct and predict dynamics of genes controlling stripes in the last common ancestor of fly and mosquito. We predict a new and different combinatorial logic of stripe formation in mosquito compared to fly, which is fully consistent with development of intermediate species such as moth-fly (Clogmia). Our simulations further suggest that the dynamics of gene expression in this last common ancestor were similar to other insects, such as wasps (Nasonia). Our method illustrates how computational methods inspired by machine learning and non-linear physics can be used to infer gene dynamics in species that disappeared millions of years ago.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1371/journal.pgen.1006052</a> <a target="_blank" rel="external noopener" href="">pmid:27227405</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC4882032</a> <a target="_blank" rel="external noopener" href="">fatcat:5izv5c23tfb65jb56luu5rncbq</a> </span>
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