Scientific American brings us a baby step closer to understanding what a bunch of strange DNA – stuff that doesn’t directly shape our cells – shared by all vertebrates is really doing in there. It helps guide the way our brains develop:
The conundrum has centred on DNA sequences that do not encode proteins, and yet remain identical across a broad range of animals. By deleting some of these ‘ultraconserved elements’, researchers have found that these sequences guide brain development by fine-tuning the expression of protein-coding genes.
The results, published on 18 January in Cell, might help researchers to better understand neurological diseases such as Alzheimer’s. They also validate the hypotheses of scientists who have speculated that all ultraconserved elements are vital to life — despite the fact that researchers knew very little about their functions.
[Stanford University’s Gill] Bejerano and his colleagues originally noticed ultraconserved elements when they compared the human genome to those of mice, rats and chickens, and found 481 stretches of DNA that were incredibly similar across the species. That was surprising, because DNA mutates from generation to generation — and these animal lineages have been evolving independently for up to 200 million years.
[Lawrence Berkeley National Laboratory genomicist Diane] Dickel and her colleagues revisited the problem using the gene-editing tool CRISPR–Cas9. In mice, they deleted four ultraconserved elements — individually and in various combinations — that lie within regions of DNA that also contain genes important in brain development. Again, the mice looked okay. But when the investigators dissected the rodents’ brains, they discovered abnormalities.
Mice lacking certain sequences had abnormally low numbers of brain cells that have been implicated in the progression of Alzheimer’s disease. And those with another ultraconserved element edited out had abnormalities in a part of the forebrain that’s involved in memory formation, as well as epilepsy.