Errors found in the mitochondrial DNA of certain people can lead to them being shorter than those without the variations, a new study has found.
The team from the University of Cambridge used data on 358,000 people from the UK Biobank and created a new technique to study mitochondrial DNA and its relationship to human diseases and certain characteristics like height.
They found that people with Scottish, Welsh or Northumbrian heritage are more likely to have a common variation in this maternal DNA.
Mitochondria are the ‘batteries’ of the cell, containing small amounts of DNA passed on from the mother, unlike nuclear DNA which comes from both parents.
Study authors found that those with errors in this form of maternal DNA could be about 2mm shorter than someone without the variations.
Errors found in the Mitochondrial DNA of certain people can lead to them being shorter than those without the variations, a new study has found (stock image)
Mitochondria also play an unexpected role in common diseases such as type 2 diabetes and multiple sclerosis, the team found.
They discovered that genetic variants in the DNA of mitochondria could increase the risk of developing these conditions, as well influence height and lifespan.
Almost all of the DNA that makes up the human genome – the body’s ‘blueprint’ – is contained within the nuclei of our cells.
Among other functions, nuclear DNA codes for the characteristics that make us individual as well as for the proteins that do most of the work in our bodies.
Our cells also contain mitochondria, which provide the energy for our cells to function by converting food into ATP, a molecule capable of releasing energy very quickly.
Each of these mitochondria is coded for by a tiny amount of ‘mitochondrial DNA’, making up only 0.1 per cent of the overall human genome.
While errors in mitochondrial DNA can lead to so-called mitochondrial diseases, which can be severely disabling, until now there had been little evidence that these variants can influence more common characteristics.
Several small-scale studies have hinted at this possibility, but scientists have been unable to replicate their findings.
Now, a team at the University of Cambridge has developed a new technique to study mitochondrial DNA and its relation to human diseases and characteristics in samples taken from 358,000 volunteers as part of UK Biobank.
Dr Joanna Howson, who carried out the work, said using this method, they looked for associations between features recorded in the biobank and mitochondrial DNA.
‘Aside from mitochondrial diseases, we don’t generally associate mitochondrial DNA variants with common diseases,’ she explained.
‘But what we’ve shown is that mitochondrial DNA – which we inherit from our mother – influences the risk of some diseases such as type 2 diabetes and MS as well as a number of common characteristics.’
Among those factors found to be influenced by mitochondrial DNA are: type 2 diabetes, multiple sclerosis, liver and kidney function, blood count parameters, lifespan and height.
Some of the effects are seen more extremely in patients with rare inherited mitochondrial diseases – for example, patients with severe disease are often shorter than average.
The team from the University of Cambridge used data on the DNA of 358,000 people in the UK biobank and created a new technique to study mitochondrial DNA and its relationship to human diseases and certain characteristics like height
The effect in healthy individuals tends to be much subtler, likely accounting for just a few millimetres’ height difference, for example.
There are several possible explanations for how mitochondrial DNA exerts its influence, the team explained, adding that one is that changes to mitochondrial DNA lead to subtle differences in our ability to produce energy.
However, it is likely to be more complicated, affecting complex biological pathways inside our bodies, according to the team.
Professor Patrick Chinnery, study co-author, said that if you want a complete picture of common disease you also have to consider the influence of mitochondrial DNA.
‘The ultimate aim of studies of our DNA is to understand the mechanisms that underlie these diseases and find new ways to treat them. Our work could help identify potential new drug targets,’ he said.
Unlike nuclear DNA, which is passed down from both the mother and the father, mitochondria DNA is inherited exclusively from the mother.
This suggests that the two systems are inherited independently and hence there should be no association between an individual’s nuclear and mitochondrial DNA – however, this was not what the team found.
The researchers showed that certain nuclear genetic backgrounds are associated preferentially with certain mitochondrial genetic backgrounds, particularly in Scotland, Wales and Northumbria.
This suggests that our nuclear and mitochondrial genomes have evolved – and continue to evolve – side-by-side and interact with each other.
One reason that may explain this is the need for compatibility. ATP is produced by a group of proteins inside the mitochondria, called the respiratory chain.
There are over 100 components of the respiratory chain, 13 of which are coded for by mitochondrial DNA; the remainder are coded for by nuclear DNA.
Even though proteins in the respiratory chain are being produced by two different genomes, the proteins need to physically interlock like pieces of a jigsaw.
If the mitochondrial DNA inherited by a child was not compatible with the nuclear DNA inherited from the father, the jigsaw would not fit together properly, =affecting the respiratory chain and, consequently, energy production.
They found that people with Scottish, Welsh or Northumbrian heritage are more likely to have a common variation in this maternal DNA
This might subtly influence an individual’s health or physiology, which over time could be disadvantageous from an evolutionary perspective. Conversely, matches would be encouraged by evolution and therefore become more common.
This could have implications for the success of mitochondrial transfer therapy – a new technique that enables scientists to replace a mother’s defective mitochondria with those from a donor, thereby preventing her child from having a potentially life-threatening mitochondrial disease.
‘It looks like our mitochondrial DNA is matched to our nuclear DNA to some extent – in other words, you can’t just swap the mitochondria with any donor, just as you can’t take a blood transfusion from anyone,’ explained Professor Chinnery.
‘Fortunately, this possibility has already been factored into the approach taken by the team at Newcastle who have pioneered this therapy.’
The findings have been published in the journal Nature Genetics.