DNA secrets long preserved in small Indonesian villages could help the health of Maori and Pacific Islanders in New Zealand.
Massey University scientists are turning to the traditional settlements, which have remained the same for centuries, as living laboratories to study how human genetics have changed.
As Indonesia effectively provided the launch pad for the settlement of the Pacific, what the scientists find could hold big implications for their descendents living today.
"Genetics is an old field now – it's been around for about 100 years," explained the study's leader, computational biologist Professor Murray Cox.
"We've known about DNA and the genetic code for 60 years.
"But we still don't really know how changes in DNA get turned into changes in how we are built, how we look and how we act."
And although we know that people have lots of differences in their DNA, it increasingly appeared that many of these changes – or even most of them – didn't actually do anything.
In the new study, supported by a $925,000 Marsden Fund grant, Cox and his colleagues will explore the genetic diversity of people on the Indonesian island of Sumba.
Specifically, they'll look at "expression levels" found in all of their genes, or which ones are turned on, off, up, or down.
"We're also going to look at epigenetic markers – little tags that mark places on the DNA and help tell cells whether to turn particular genes on or off," Cox said.
"By combining these datasets, we can begin to reconstruct which DNA changes are actually associated with changes to the expression of genes."
The logic behind the study was that, if a gene's expression doesn't change, the associated DNA changes likely had little to no purpose.
"This project will hopefully begin to tell us which DNA changes have an effect on us, versus those that likely don't."
The small Indonesian communities offered ideal places to study, as their residents still led very traditional lifestyles, free of many of the effects that had changed modern, westernised societies.
"People and their ancestors have been living in these villages for so long that they are now genetically different too; you can guess what village a person came from by looking at their DNA," Cox said.
"However, the environment is relatively similar, so we can begin to 'control for' environmental factors."
Although there had been many large-scale genetic studies, involving thousands of people, these had typically drawn on Caucasians from the US or Europe, and didn't represent New Zealand's diversity very well.
Cox pointed out that Indonesian communities had been something of a staging area for the populating of the Pacific.
"The people we are studying are the direct ancestors of many New Zealand communities, including Maori and Pasifika."
It wouldn't be without its challenges.
To study gene expression, scientists need to sample RNA, a sister molecule to the better-known DNA.
DNA is stable – it can be spit into a tube and sent to a genetic testing company in the US for sampling weeks later - but RNA breaks down quickly.
"Getting good RNA samples from extremely remote populations in places like eastern Indonesia is very hard."
Another obvious problem was trying to study the DNA data of individuals. Each person carries four billion building blocks of DNA - alongside RNA and epigenetics data.
"A large part of the work will therefore be on developing the approaches and tools needed to put these different datasets together and to pull out the information that is biologically important – wheat from the chaff.
"The initial goal is to provide foundational understanding that future work can build on.
"How do DNA differences turn into differences in how we are built? We need to understand this before we can do anything more directly useful."
Longer term, the aim will be to identify DNA changes that have medically relevant outcomes.
"Perhaps some people respond better to one drug rather than another; or people respond better to one type of treatment instead of a different one.
"This is especially important for understudied groups, like Maori and Pasifika, because treatments optimised for middle-aged white American men might need to be improved for these other populations.
"By studying a sister group to these communities, this study will hopefully provide baseline information on genetic diversity that will be useful for these later goals."