What cheetahs, armadillos revealed about human DNA

It has been 20 years since scientists put together the first rough draft of the human genome, the three billion genetic letters of DNA tightly wound inside most of our cells. Today, scientists are still struggling to decipher it.

But a batch of studies published in Science on Thursday has cast a bright light into the dark recesses of the human genome by comparing it with those of 239 other mammals, including narwhals, cheetahs and screaming hairy armadillos.

By tracing this genomic evolution over the past 100 million years, the so-called Zoonomia Project has revealed millions of stretches of human DNA that have changed little since our shrew-like ancestors scurried in the shadows of dinosaurs. These ancient genetic elements most likely carry out essential functions in our bodies today, the project found, and mutations within them can put us at risk of a range of diseases.

The project’s strength lies in the huge amount of data analyzed — not just the genomes, but experiments on thousands of pieces of DNA and information from medical studies, said Alexander Palazzo, a geneticist at the University of Toronto who was not involved in the work. “This is the way it needs to be done.”

The mammalian genomes also allowed the Zoonomia team to pinpoint pieces of human DNA with radical mutations that set them apart from other mammals. Some of these genetic adaptations may have had a major role in the evolution of our big, complex brains.

The researchers have only scraped the surface of potential revelations in their database. Other researchers say it will serve as a treasure map to guide further explorations of the human genome.

“Evolution’s crucible sees all,” said Jay Shendure, a geneticist at the University of Washington who was not involved in the project.

Scientists have long known that just a tiny fraction of our DNA contains so-called protein-coding genes, which make crucial proteins like digestive enzymes in our stomach, collagen in our skin and haemoglobin in our blood. All of our 20,000 protein-coding genes make up just 1.5 percent of our genome. The other 98.5 percent is far more mysterious.

Scientists have found that some bits of that inscrutable DNA help determine which proteins get made at certain places and at certain times. Other pieces of DNA act like switches, turning on nearby genes. And still others can amplify the production of those genes. And still others act like off switches. Through painstaking experiments, scientists have uncovered thousands of these switches nestled in long stretches of DNA that seem to do nothing for us — what some biologists call “junk DNA.” Our genome contains thousands of broken copies of genes that no longer work, for example, and vestiges of viruses that invaded the genomes of our distant ancestors.

But it’s not yet possible for scientists to look directly at the human genome and identify all the switches. “We don’t understand the language that makes these things work,” said Steven Reilly, a geneticist at the Yale School of Medicine and one of more than 100 members of the Zoonomia team.

Zimmer writes the “Matter” column for NYT©2023

The New York Times