In humans, worms and flies, shared genetics

WORMS
Photo by Annelisa Leinbach.

A new Yale-led study may show that humans, worms and flies are, on a fundamental level, not so different.

The researchers performed a comprehensive analysis of the transcriptome — or product of genetic information — across the three species. The team, headed by Yale professor of molecular biophysics and biochemistry Mark Gerstein, discovered similarities in how key regions of the genome are expressed. This striking similarity allows researchers to investigate humans by looking at the genomes of worms and flies, facilitating research that would otherwise be unethical. The findings appeared in the journal Nature on Aug. 27, 2014.

“I think the big implications for the paper are when you can find something really ancient and really conserved,” Gerstein said. “It helps you better annotate and understand the human genome.”

While past research had created similar quantitative models of gene regulation, the new study produced a more detailed model of how and when different genes are expressed. To build the models, researchers took RNA sequences from the three organisms and performed the same analysis on each species to facilitate comparison between flies, worms and humans.

The first model found an area of the genome in humans, worms and flies that was expressed in concert. The model revealed 16 areas in the genome with this pattern of activity across the three species, and Gerstein said many play important roles in development. The other model analyzed histones, structures in the nucleus of cells that are key in regulating gene expression. This second analysis revealed that regions important in controlling gene expression were found in similar locations of the worm, fly and mouse genomes.

In sum, the models reveal that gene regulation is conserved among the species, said Daifeng Wang, a study author and Yale postdoctoral associate in molecular biophysics and biochemistry.

This new insight into evolutionary genetics across species enhances researchers’ understanding of human genetics, and the implications of this study are broad, said Deyou Zhang, a professor of genetics at the Albert Einstein College of Medicine.

“For most of our research, we cannot use humans [for experiments],” he said. “So this means that we can use worms or flies as a model. People should use this data for their own research.”

For Gerstein, the research also holds promise for interpreting individual genomes and personalizing treatment for conditions such as cancer.

According to the Human Genome project, the human genome contains approximately three billion base pairs of DNA.

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