This single-letter change is not in a gene, but in a piece of DNA that influences gene expression, called an enhancer. The change altered the level of gene expression, measured in keratin-producing cells grown in a dish, by only 20 percent. This relatively small difference in gene expression causes a very noticeable physical difference in hair colour.
'This isn’t a "turn the switch off", it’s a "turn the switch down"', said Professor David Kingsley from Stanford University, who led the research team.
The researchers studied a gene called KITLG important for cell organisation, and known to be involved in skin and hair colour in sticklebacks, mice and humans. The team put the human form of the enhancer DNA sequence into mice, so that it controlled the expression of mouse KITLG. Mice with the 'blonde' version of the human sequence had noticeably paler fur than mice without this single letter change.
This study has implications for looking at the role of genes in producing physical characteristics, as it implies that small changes in the amount of protein produced from a gene can have a large physical effect.
'Dialing up and down the expression of an essential growth factor in this manner could be a common mechanism that underlies many different traits', said Professor Kingsley.
It also illuminates how genes which may cause large developmental problems if mutated directly can still be involved in the production of physical variation. Changes in enhancer DNA can affect gene expression in one cell type but not others.
This is why this type of blond hair is not strongly linked to a particular skin or eye colour, as the DNA change studied only alters protein expression in the cells in hair follicles. 'This particular genetic variation in humans is associated with blonde hair, but it isn't associated with eye colour or other pigmentation traits', Professor Kingsley added.
Earlier studies of genetic variation in humans have linked at least eight different DNA regions to blondness, when a DNA sequence was found in people with blonde hair but not in people with other hair colours. The particular DNA sequence examined in this study is one found in blond people of northern European ancestry.
The research was published in Nature Genetics.