Every living thing carries a story in its DNA. Scientists read that story to understand how a species has changed, how healthy it is, and how likely it is to stick around in the future. But what happens when they read the story using the wrong guidebook?
That’s the problem with something called a reference genome – a kind of master blueprint that scientists use to compare genetic data. If the reference genome doesn’t actually belong to the species being studied, it can lead to totally wrong conclusions.
Gray foxes are common wild canines in North America. They’ve been around for a long time, adapting to all sorts of environments from forests to deserts.
When scientists tried to study gray fox DNA, they didn’t always have a proper reference genome. Instead, they often used the genome of a domestic dog or an Arctic fox.
Using these mismatched genomes made gray fox populations look smaller, less genetically diverse, and even in decline – even when they were actually doing fine or growing.
“It turns out the reference you use really changes the story you tell about a species,” said Jazlyn Mooney, the lead author of the study from USC Dornsife.
“If you use the wrong reference, you can end up with misleading answers about a species’ history or health, and even its chances of long-term survival.”
To see just how much a reference genome can mess things up, the researchers studied the DNA of 12 gray foxes – six from the eastern U.S. and six from the west.
Next, the team ran three comparisons using different reference genomes: one from the gray fox itself, one from a domestic dog, and one from an Arctic fox. The results were all over the place.
When the gray fox’s own genome was used, scientists found 26% to 32% more genetic differences between individuals. They also found about a third more rare variants – these are small changes that give clues about recent evolution.
Population size estimates were 30% to 60% higher using the correct reference. In the western U.S., the gray fox genome showed stable or growing populations. But when scientists used the dog or Arctic fox genomes, the data falsely pointed to population decline.
The wrong reference genome also threw off measurements of how DNA mixes during reproduction. In some cases, the numbers were double or triple what they should have been, especially near the tips of chromosomes.
“This is the kind of thing that could change conservation decisions,” said Mooney. “If you think a population is shrinking when it’s not, or vice versa, you might end up protecting the wrong group or missing an opportunity to safeguard genetic diversity.”
When scientists look for signs of natural selection in DNA, they’re often searching for “hotspots” – areas that suggest a species is adapting to its environment.
The dog and Arctic fox genomes showed twice as many of these hotspots compared to the gray fox genome. Most of them were false alarms caused by the species mismatch.
Conservation decisions rely on knowing which genes are under pressure and how animals are adapting. A bad genome map can lead scientists down the wrong path.
A messed-up DNA map can throw off research for lots of species, especially the ones already fighting for survival. Animals like the Ethiopian wolf, the African wild dog, and the tiny Channel Island foxes off Southern California’s coast could all be affected.
Conservation groups use genetic data to figure out which populations need help, how to manage breeding programs, and whether species are at risk of inbreeding. If that data is off, the whole plan could collapse.
“Maintaining the world’s biodiversity isn’t just about saving animals for their own sake,” Mooney said.
“Biodiversity supports clean water, food security and climate stability. If conservation plans are based on incomplete or biased genetic information, we risk mismanaging species and weakening the natural systems people depend on.”
Only about 1% of species have their own reference genome. Building one isn’t cheap, but the benefits are clear. A high-quality, species-specific genome gives scientists a much sharper view of what’s happening – and what needs to be done.
Mooney and her team say there are newer, cheaper computational tools that can help improve genome quality, especially when creating a reference from scratch. These tools can help reduce bias and better represent genetic diversity.
“We’re not saying every species will be as impacted as gray foxes,” Mooney said. “But our study shows the risks are real, and can lead you astray.”
When it comes to understanding and protecting wildlife, using the right map isn’t a luxury. It’s a necessity. Otherwise, conservation might end up chasing shadows – and missing the real story written in the DNA.
The full study was published in the journal Cell.
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