Insight into genetic origin ‘providing valuable ways to fight disease’

TCD research project lifts lid on ancient disease genes and opens way for new treatments

‘If we identify changes in the disease genes this is important as it might, potentially, be the cause of a genetic disease.’ File photograph: Getty

‘If we identify changes in the disease genes this is important as it might, potentially, be the cause of a genetic disease.’ File photograph: Getty

 

Scientists have discovered how “disease genes” evolved in vertebrates 500 million years ago, shedding light on human genetic origins and enabling new ways of diagnosing and treating diseases.

“What we have done is to make a really significant improvement in our ability to reconstruct the past genome,” says Prof Aoife McLysaght, based at the Molecular Evolution Lab attached to Smurfit Institute of Genetics in Trinity College, who took part in research reported in Nature Communications.

“This research tells us where we’ve come from,” says McLysaght. “And by better knowing our origins we can better understand human diseases, why they occur, and also things like the evolution of our immune system – something which is very ancient.”

McLysaght is interested in the genetic evolution of the early vertebrates. “We’ve known that there were genome duplications when the vertebrates emerged 500 million years ago . . . but there was a question about whether it was two rounds of duplication or one. In this work, we’ve confirmed now that there were two rounds; one of which was ancestral for all vertebrates and one which was ancestral for us.”

It’s significant for all of us that disease genes were retained in duplicate in our genome after this ancient duplication event. “That tells you not that they are bad, but that they are really important genes which – if they go wrong – it results in disease.”

Investigating the evolution of ancient genes is challenging because DNA degrades over time. “It’s not possible to sequence ancient DNA from 500 million years ago, so other methods are needed to map genetic evolution.”

Dr Yoichiro Nakatani, a mathematician, played a key role in the research, says McLysaght, by realising that a statistical model developed for document analysis could be useful for ancient gene analysis.

“He saw that the document analysis problem was the same problem that we were looking at,” she says.

Fragile genome

The model provided insights into how disease genes are retained in duplicate in the genome and how fragile they can be. “If there’s too much or too little, then things can go wrong,” adds McLysaght.

When scientists understand what can go wrong with disease genes, they can start to fix the problem, she says. “For instance, if there is an excess of something then there might be a drug available that can dampen it down.”

New insights into how genes evolved, and how they relate to one another, can also help provide insight into genetic conditions. “If you want to say which genes are potentially disruptive in a disease then it helps to know its evolutionary information to put some genes on the shortlist,” says McLysaght.

“If we identify changes in the disease genes this is important as it might, potentially, be the cause of a genetic disease. The study of these ancient genes is making the investigation of genetic conditions more efficient and can lead to better diagnoses and treatments in the future,” she adds.