By Marcia-Ruth Ndege ’21

In human embryos, the brain begins to develop during the first trimester of pregnancy. Proper brain development is critical at its early stages and could have detrimental effects if something goes awry. Scientists and researchers have investigated and familiarized themselves with the basics of brain development. A new study has shown that an unexpected participant plays a major role in this process. They are known as ultraconserved elements: long sections of DNA that do not code for proteins but are present in our genes. These elements are present identically in the genes of all vertebrates.

Ultraconserved elements were first discovered in 2005 by Professor Gill Bejerano, a genomicist from Stanford University. In comparing the human genome to those in rats, mice, and chickens, they discovered 481 stretches of DNA that were similar. Scientists have long believed that ultraconserved elements were conserved among the species because of their importance, but they didn’t know why. In an experiment, Bejerano and his team eliminated some of these non-coding sequences from mice DNA and found that the mice looked and reproduced normally: an inconclusive result. More recently, Diane Dickel and her team from the Lawrencce Berkeley National Laboratory proceeded to remove some of these sequences from genes that code for brain function by using the gene editing tool, CRISPR-Cas9. At first glance, the mice appeared normal, but a dissection of their brains told a different story; they had low numbers of brain cells, leaving them prone to Alzheimer’s, epilepsy, and difficulties with memory formation.

This integral discovery has paved the way for future studies in humans. The results show a direct relationship between brain development and the ultraconserved genes as well as the subsequent diseases. Researchers will soon be able to determine if human candidates with Alzheimer’s, epilepsy, and memory formation problems have abnormalities in their ultraconserved genes, allowing the development of more targeted treatments.

References:

1. A. Maxmen, “Dark matter” DNA influences brain development. Nature (2018).
2. Image retrieved from: https://pixabay.com/en/dna-biology-medicine-gene-163466/