(Washington State University) A Washington State University student’s undergraduate research is challenging a widely held assumption on the best way to analyze old DNA in anthropological and forensic investigations. Sarah “Misa” Runnells’ claim is weighty enough to be published this week in the peer-reviewed, online journal PLoS ONE. At issue is the best way to sequence “ancient” DNA, bits of genetic code pulled from remains up to 800,000 years old.

What caused the extinction of the mammoth while other ice age mammals like the musk ox survived to present day? A new scientific methodological approach to detect genetic material will help researchers to solve the many mysteries of the past.

“I’m confident that the new methodological approach, will be of great importance to molecular biology”, says Professor Eske Willerslev at the Centre for Ancient Genetics, University of Copenhagen. One of his PhD students recently came up with a brilliant idea enabling researchers to get a full view of total ecosystems or populations dating thousands of years back in time. What usually has taken the DNA-researchers several years of laboratory work can now be done in just a few hours.

The automation of a long research process

Professor Eske Willerslev and his team find DNA traces of ancient life in areas where the ground is permanently frozen like in Siberia or Alaska. Here, inside the frozen ground, the team is able to find ancient DNA material from animals and plants that used to live in the area thousands of years ago. In order to detect the types of DNA material in a sample, the researchers normally use a DNA primer – a kind of ‘fishing hook’ attached to a specific piece of DNA. That particular piece of DNA is then being multiplied, cloned and sequenced which makes it possible for the researchers to identify it. However, this procedure is slow, and it takes years just to identify a fraction of the most common animals and plants available from the many DNA samples.

The technology

A new sequencing machine capable of interpreting millions of pieces of DNA in just a few hours was recently introduced. The machine alone brought in a revolution to the field, but has certain disadvantages and shortcomings. Firstly, an analysis made by the machine is quite expensive. Each analysis costs approximately DKK 45,000 and although the machine reads extensive amounts of DNA material, the cost is still considerable to a research project. Secondly, a vital problem arises when researchers try to benefit from the machine’s enormous capacity by analysing samples from multiple locations or specimens in a single run in order to reduce costs. The machine simply cannot separate more than 16 samples from each other.

Eske Willerslev went to check out the machine for himself at the Danish Cattle Research Centre in Foulum – the only place in Denmark, which operates the new sequencing machine. He realised to his great disappointment that the researchers at the University of Copenhagen could not make use of the machine for their respective projects due to the disadvantages mentioned above.

A simple but brilliant idea!

Then Jonas Binladen, a PhD student from his team, came up with a simple but brilliant idea: By attaching a ‘finger-print’ to the tagged primers (‘fishing hooks’ used to amplify DNA from each sample), one should – in theory – be able to localise each of the million sequences produced in each run, to its original sample or specimen. By making it possible to process amplification products from multiple samples or specimens in the same run, the team could make use of the machine’s great capacity.

The research team now wanted to test the idea. And it really did work! The results are now being published in the scientific web magazine PLoS ONE Publication.

According to Eske Willerslev, the new approach have great scientific potentials:

“Today, when using conventional methods to detect ancient DNA, we are only able to test a limited number of samples providing us with a somewhat random image of life in the past. Due to this new method, our knowledge will be put into a whole new perspective. For instance, finding out if species became endangered due to a dramatic change in the climate or if the decline in numbers started many years earlier than we originally thought or estimated”.

Contact:

Eske Willerslev, professor, Centre for Ancient Genetics, Phone: +45 3532-0570, Mob. +45 2875-1309 ewillerslev @ bi.ku.dk,

Jonas Binladen, PhD – student, Centre for Ancient Genetics, Mobile: +45 6067-2620, JBinladen @ bi.ku.dk

Woolly mammoth replica in a museum exhibit in Victoria, British Columbia, Canada. Foto: Encyclopædia Britannica