Professors Robert Lightowlers and Doug Turnbull of the University of Newcastle's Mitochondrial Research Group owe a special debt to Fred Sanger. Not just because of his two Nobel Prizes, the second of which (for his work on DNA sequencing) laid the foundations for their field. But also for a remarkable feat of memory...

"Can you imagine? After 20 years, finding a test-tube the size of the smallest part of your little finger, somewhere in the Sanger labs, which must cover half of Cambridge!" Professor Turnbull laughs: "I suppose it fits: only a sequencer would have the right kind of mind!"

That test-tube contained the original DNA sample which, in the late 1970s, Dr Sanger's group used to sequence the first human genome - the 16 500 base pair human mitochondrial DNA. Now known as the 'Cambridge Reference Sequence' (CRS), it has been an indispensable reference for studies of human evolution, population genetics and mitochondrial disease since its publication in 1981.

But what did the Newcastle Group want with the original sample? The story begins in Texas, where Professors Turnbull and Lightowlers, funded by a Biomedical Research Collaboration Grant from the Wellcome Trust, were visiting Professor Neil Howell. The main aim of the study was to combine the Texas group's fundamental knowledge of mitochondrial genetics with their own more clinically related studies. They found Professor Howell increasingly frustrated by apparent differences between the CRS sequence and what was known from other research.

Mitochondrial DNA (mtDNA) has two unusual characteristics. First, it is extremely variable: mutations are common. And second, it is inherited only through the maternal line: mutations can be clearly followed through generations. They act as 'markers' that help to track different human populations and ethnic groups.

But in the CRS some of these common markers 'didn't fit' - in particular, there was a non-European mutation bang in the middle of the reference sequence for European groups. Errors in the original sequencing were one possible explanation, but the differences could simply have reflected individual variation. Not knowing what lay behind the differences was a frustrating stumbling block.

After the visit, Professor Lightowlers decided to phone Professor Alan Coulson in Cambridge with a bizarre request - did any of the original material still exist? Professor Coulson enthusiastically offered to contact Dr Sanger, who had been retired for some time. "And," Professor Lightowlers continues, "He knew where it might be - not only which freezer, but whereabouts in the freezer - and he came in and found it!"

Links

Professor Robert Lightowlers, University of Newcastle upon Tyne: Research page

Professor Doug Turnbull, University of Newcastle upon Tyne: Research page

Caption

Fred Sanger's group sequenced the first human genome – the mitochondrial genome – in the late 1970s.