Two species of worms, separated by 20 million years of evolution, have been found to activate their genes in nearly identical ways as they develop from a single cell to a fully formed organism. In a new study, researchers at the Perelman School of Medicine at the University of Pennsylvania and the University of Washington School of Medicine have revealed this remarkable conservation in two transparent roundworms, Caenorhabditis elegans and Caenorhabditis briggsae. The findings, published this month in Science, show that gene expression patterns remain stable in cells with broad functions, offering new insights into how evolution shapes development across species, potentially including humans.
We've been studying the evolution of development for decades, but this is the first time that we've been able to compare development in every single cell of two different organisms."
Junhyong Kim, PhD, professor of biology and director of the Penn Genome Frontiers Institute, a co-senior author of the study
Worms' Gene Patterns Defy Evolutionary Time
The goal of the study was to compare gene expression in every cell type of the two worms to determine what changes had occurred since they split from their common ancestor. To do this, the researchers measured levels of messenger RNA in every cell at various stages of embryonic development using a technique called single-cell RNA sequencing. Messenger RNA, or mRNA, carries the instructions for making proteins from active genes to the cell's protein-making machinery. High levels of mRNA from a gene indicate it is active; low levels mean it is inactive.
Using the technique, the researchers tracked the changes in the individual cells through the worms' embryonic development from when the embryo is a ball of 28 mostly undifferentiated cells to when most cell types are in place, a process that takes about 12 hours.
Kim said the finding that while gene expression aligns with the worms' body structures, the discovery that changes in gene expression had no impact on their body plan was unexpected.
"It was just remarkable, with this evolutionary distance, that we should see such coherence in gene expression patterns," said Robert Waterston, Md, PhD, professor of genome sciences at the University of Washington School of Medicine and a co-senior author of the paper. "I was surprised how well everything lined up."
Specialized Cells Drive Evolutionary Gene Changes
When gene expression did diverge between the two worms, the changes were more likely to occur in specialized cell types. For example, expression patterns in cells involved in basic functions like muscle or gut tended to be conserved, while expression patterns in more specialized cells involved in sensing and responding to the worm's environment were more likely to diverge.
"Genes related to brain activity, for example, seem to diverge more rapidly-perhaps because changes were needed to adapt to new environments-but for now, that's speculation," said Christopher R. L. Large, a postdoctoral researcher in the department of genetics at the Perelman School of Medicine at the University of Pennsylvania and the paper's lead author.
The study describes where and when gene expression patterns differ between the species but doesn't yet explain why, said John Isaac Murray, PhD, associate professor of genetics in the Perelman School of Medicine and the study's third senior author.
"It's hard to say whether any of the differences we observed were due to evolutionary adaptation or simply the result of genetic drift, where changes happen randomly," he said. "But this approach will allow us to explore many unanswered questions about evolution."
This research was supported by grants from the National Institutes of Health (HD105819, HG010478 and HG007355) and the National Science Foundation (PRFB2305513).
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