Scientists calculate mutation rate in human genome

Scientists based at the Wellcome Trust Sanger Institute, in Hinxton, Cambridge, UK, have used 'next generation sequencing technology' to work out the mutation rate in the human genome. The international team's findings were published in Current Biology last week.

Every person has three billion 'letters' of DNA that make up the human genome. A mutation occurs when one of these letters changes. The international team co-ordinated by Dr Chris Tyler-Smith, have found that the mutation rate is one mutation in every 15 to 30 million letters per generation, which means each person has 100-200 new mutations in their DNA.

Most mutations are harmless, and do not affect how our bodies function or look. However, some mutations can directly lead to diseases such as cancer. The mutation rate has been estimated before, back in 1935 by J.B.S Haldane, one of the founders of modern genetics. He was studying haemophilia and estimated that there would be a one in 50,000 incidence of mutations in the haemophilia gene - the equivalent of a mutation rate of one in 25 million in the whole genome. Others have measured rates at different specific genes or compared DNA from humans and chimpanzees to produce general estimates of the mutation rate.

The team at the Sanger Institute have now accurately calculated the mutation rate. They sequenced the same piece of DNA - just over 10,000,000 letters from the Y chromosome - from two men separated by 13 generations, whose common ancestor lived 200 years ago. They counted the difference between the two sequences and found only four mutations. From their data they were able to calculate the mutation rate.

'These four mutations gave us the exact mutation rate - one in 30 million nucleotide each generation - that we had expected', says Dr Tyler-Smith. 'This was reassuring because the methods we used - harnessing next-generation sequencing technology - had not previously been tested for this kind of research. New mutations are responsible for an array of genetic diseases. The ability to reliably measure rates of DNA mutation means we can begin to ask how mutation rates vary between different regions of the genome and perhaps also between different individuals'.

Understanding mutation rates is key to many aspects of human evolution and medical research; mutation is the ultimate source of all human genetic variation. Mutation rates also provide a molecular clock for measuring evolutionary timescales. With better measurements of mutation rates, we could improve the understanding of evolution, or test ways to reduce mutations, for example.

'The amount of data we generated would have been unimaginable just a few years ago', says Dr Yali Xue from the Wellcome Trust Sanger Institute and one of the project's leaders. 'But finding this tiny number of mutations was more difficult than finding an ant's egg in the emperor's rice store'.