Most people harbour at least one lethal mutation

Geneticists have estimated that each of us carries an average of one or two lethal, but recessive, genes in our DNA.

Researchers from the University of Chicago, USA, arrived at this conclusion by studying the Hutterite community - a genetically isolated and distinct population in South Dakota. 

The Hutterites are a religious group that travelled to North America from Germany in the 1870s. The community has kept exceptionally complete genealogical records going back 13 generations and detailing the lineage of more than 1,600 individuals, making them ideal for the study. Members of the community also have equal access to food and medical treatment, which meant that the researchers could eliminate these factors in their analysis.

'Their records offered a fantastic opportunity to estimate the burden of recessive lethal mutations in a new way that disentangles the effects of genetic and socioeconomic factors,' said Ziyue Gao, the study's lead author.

Gao and her team used a sophisticated computer model to determine how many recessive lethal genes lay in the Hutterite gene pool. They ran simulations using data on genetic diseases that were already known to exist in the Hutterite population, and they used the extensive genealogical records to predict whether these recessive genes came from the founder population. They compared their analysis with living Hutterites who have genetic diseases and found that there must have been 0.58 recessive lethal genes per founding member.

Studies in mice show that around half of individuals that inherit two copies of a lethal recessive gene die before birth. This led the team to the final conclusion that each founder member of the Hutterites actually carried one or two lethal and recessive genes within their genome.

'This number is probably lower than the real average for most populations, but it is in the same ballpark,' said Gao. Small populations like the Hutterites probably have fewer lethal recessive genes in their gene pool because natural selection is more likely to root them out, so the general population may have more recessive lethal genes to contend with.

Surprisingly, the recessive disease mutation estimate for humans is similar to those from fruit fly and fish species, even though these organisms have very different total genome sizes. 'We don't yet understand why the number of recessive lethal mutations might be relatively constant across distantly related organisms,' said Gao. 'It's an interesting evolutionary question for further research.'