By identifying overlooked genetic material inherited from Neanderthals and our other close relatives in the past, Dr. PingHsun Hsieh hopes to better understand how human evolution continues to influence human biology and disease risk today.

What Ancient DNA Could Teach Us About Health Today

By identifying overlooked genetic material inherited from Neanderthals and our other close relatives in the past, Dr. PingHsun Hsieh hopes to better understand how human evolution continues to influence human biology and disease risk today.

Why do some people have a greater risk of developing diabetes, heart disease or autoimmune conditions than others? Part of the answer may be hidden in DNA passed down from our ancestors tens of thousands of years ago.

Dr. PingHsun Hsieh, a University of Minnesota researcher with appointments in the Medical School and the College of Biological Sciences, is developing new ways to find out how genetic changes over the evolutionary timescale may still affect people today, including genetic material inherited from Neanderthals and to study how it may affect people today.

Dr. Hsieh studies human evolution, biology and disease across different populations. His laboratory uses advanced DNA sequencing and computational tools to examine parts of the human genome that were previously difficult to study. For years, scientists have known that many modern humans carry some Neanderthal DNA. That genetic material entered the human gene pool when early modern humans interbred with Neanderthals, and some of those inherited differences may have helped people survive in past environments.

An interesting twist about evolution is that the same differences could affect the body in new ways. “Something good happened in the past, but now we are in the modern day, and the environment has also changed,” Dr. Hsieh says.

For example, a genetic change that helped the body conserve energy during periods of food scarcity might have been useful thousands of years ago. But in a modern environment where food is more readily available, that trait could potentially contribute to conditions such as type 2 diabetes.

Dr. Hsieh’s team is working to identify these inherited genetic variants so that researchers can begin understanding what they actually do today.

“Once you identify variants, what those mutations do is still a question mark,” Dr. Hsieh explains. “Large collections of biobank data give us a great opportunity to understand their potential biological impact in humans.”

The researchers began with genomic data from about 50 people representing several human populations. They used long-read sequencing, a technology that can examine larger and more complicated sections of DNA than traditional methods. They also developed machine learning models that help detect patterns resembling Neanderthal DNA in modern human genomes, especially in large, difficult-to-sequence regions.

This work recently culminated in a study published in Science, in which Dr. Hsieh and his colleagues created a global map of structural genetic variants inherited from Neanderthals and Denisovans. The findings revealed previously overlooked pieces of archaic DNA and identified variants that may have contributed to human adaptation.

The initial study is a starting point. Dr. Hsieh’s lab is working with collaborators to expand the research to more than 10,000 people across diverse populations. A larger and more diverse group will allow the team to estimate more accurately how common certain Neanderthal-derived variants are across populations.

“We are hoping we can identify more missing pieces that could not be found in the past because of limitations in sequencing technology,” Dr. Hsieh says.

The next step is to compare these variants with information from large biobanks, which connect genetic data with electronic health records. That could help researchers determine whether particular variants are associated with cardiovascular disease, type 2 diabetes, autoimmune conditions, or other health issues.

This research is not expected to change patient care immediately. Instead, it is building a foundation for future studies and a deeper understanding of human DNA. By identifying genetic differences that have been overlooked, researchers may gain a clearer picture of how inherited genetics and modern environments work together to influence human biology and health.

Says Dr. Hsieh, “We are interested in human evolution and how we became who we are today.”