Kiwi scientists have used DNA to unravel the complex history of one of New Zealand's most enduring and least wanted creatures - the mouse. What they discovered could prompt a rethink about how we use genetics to interpret ancestry, writes science reporter Jamie Morton.


Today's New Zealand is a melting pot of cultures - many of us descending from voyagers who arrived here from far-away lands over past centuries.

Reconstructing the history of our ancestors - where they came from, where they arrived, and when - has been made easier with incredible leaps in DNA technology.

But the focus hasn't just been us and our forebears, but also, those smaller, furrier immigrants that stowed away below decks and arrived here to find an unspoiled paradise teeming with prey.

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The first rodent explorers that journeyed across the oceans were the kiore, or Polynesian rat, which travelled alongside Maori and are estimated to have arrived here around 1280 AD.

The whakapapa of kiore has helped reveal the routes and timing of the great Polynesian voyages across the Pacific.

Later, from the 1820s onwards, other rodents, including the house mouse, arrived hidden away in the supplies of boats coming from all around the world with settlers, sealers, whalers and traders.

"These mice are, like its people, diverse, with whakapapa tracing across the globe," said Dr Andrew Veale, a Unitec lecturer and co-author of a new study just published in scientific journal Royal Society Open Science.

"Traces of this ancestry can be uncovered from the DNA of the mice now living here, and from this information we can tell an amazing story of colonisation, invasion, replacement, and population mixing."

Scientists draw on the two different types of DNA that make up our bodies: mitochondrial DNA, which is inherited maternally, and nuclear DNA, which is passed down from both parents.

Mitochondrial DNA codes for only one process – generating energy in the cells.
Nuclear DNA, meanwhile, determines everything else about us – how we develop, the colour of our eyes and hair - and even whether we sneeze when we look at the sun.

"Because mitochondrial DNA is inherited along one ancestral line without mixing, it is an ideal marker to trace your origins," Veale explained.

"The majority of scientific research tracing origins using DNA – literally thousands of studies, have primarily focused on mitochondrial DNA."

For instance, it analysis of human mitochondrial DNA that formed the basis of the recent "out of Africa" hypothesis, suggesting that all living humans could trace their maternal ancestry to a single woman - dubbed "Mitochondrial Eve" - who lived in Africa around 190,000 years ago.

The first voyagers to New Zealand brought the kiore, or Pacific rat, from Polynesia. Photo / File
The first voyagers to New Zealand brought the kiore, or Pacific rat, from Polynesia. Photo / File

Just like humans, mice have a fascinating diversity of genes, which, when analysed, can show how their populations have expanded and evolved.

In their native range, the species Mus musculus – better known as house mice, consists of three closely related subspecies with largely separate distributions: M. m. musculus found in Eastern Europe and Northern Asia, M. m. castaneus found in Southeast Asia and India, and M. m. domesticus, native to western Europe, the Near East, and northern Africa.

These three subspecies look different to each and are genetically quite distinct, having evolved separately for around 350,000 years.

Several years ago, Veale and Professor Carolyn King, of Waikato University, began a project tracking the mitochondrial DNA of New Zealand's mice.

They discovered an astonishing amount of genetic diversity, concluding that mice of the three main subspecies had mixed and hybridised to create the populations we have here today.

"Hybrids between subspecies are known to have numerous genetic problems, and in particular, domesticus-castaneus hybrids have rarely been studied in the wild due to genetic incompatibilities and non-overlapping ranges," Veale said.

"This makes studying the genetics of New Zealand mice extremely interesting."

Remarkably, they were able to obtain such high resolution information about the origins of New Zealand mice that we were able to suggest the specific boat that some mice travelled on.

"Our genomic information shows Antipodes Island mice are likely to be French, and given the historical evidence of shipwrecks and invasion timing, they therefore probably arrived on the President Felix Faure, a four-masted barque which was wrecked there in 1908."

Mice on Ruapuke Island, south of Bluff, were Australian emigrants.

Their ancestors had probably arrived on the Elizabeth Henrietta, which stranded on the island during the ship's voyage from Sydney in 1824.

While Veale and King found out that mice had arrived many times, from many places, they still didn't have the full picture.

"Where exactly did all of these mice come from, and how have they mixed since they got here?

The distribution and colonisation routes of each of the three mouse subspecies in New Zealand today. Image / Supplied
The distribution and colonisation routes of each of the three mouse subspecies in New Zealand today. Image / Supplied

"We couldn't answer these questions with mitochondrial DNA alone, so we looked at cutting edge technology recently developed for looking at the mouse nuclear genome."

Because mice are a model organism used in biomedical and developmental biology research, cheap genomic marker sets have been developed for analysing their genomes.

The researchers took advantage of these marker sets, and sequenced 150,000 SNPs - each representing a difference in a single DNA building block - for 161 mice from across New Zealand.

The results, Veale said, were "extremely surprising".

"The hybrid domesticus-castaneus populations in New Zealand on Chatham Island and in the southern half of the South Island are actually hybrids only in the very limited sense - they have different mitochondrial and nuclear ancestry.

"Both of these populations are essentially pure M. m. domesticus across the nuclear genome, but they retain the mitochondrial 'ghosts' of a previous hybridisation event which failed to lead to nuclear genetic mixing in the long term."

No traces of their Asian ancestry remained in their nuclear genomes.

"We had previously thought that these mice had come directly from China, perhaps from sealers returning from the Canton fur markets, but now we can see that almost all of their ancestry came from western Europe.

"To put how unusual this in context, it would be similar to you going to the doctor for a genetic test, and being told that one of your mother's relatively recent ancestors was a chimpanzee – these mice had the wrong mitochondrial genomes.

"The spatial patterns of ancestry for mice across the country therefore was therefore completely different from what we had believed given the mitochondrial data."

How could that happen?

Mice are considered a major pest today and a target of large-scale conservation efforts. Photo / File
Mice are considered a major pest today and a target of large-scale conservation efforts. Photo / File

Having mitochondria that didn't match the rest of your genome was not as strange as it sounds, Veale said, because of the different ways the two kinds of DNA are inherited.

"When an M. m. castaneus mother mates with an M. m. domesticus father, their offspring are 50-50 domesticus/castaneus at a nuclear level, but 100 per cent castaneus mitochondria.

"If the female offspring were then to mate with an M. m. domesticus male, on average they would be 25 per cent castaneus, 75 per cent domesticus for nuclear DNA, but still 100 per cent castaneus for their mitochondria.

"After only six generations, they are over 98 per cent domesticus, though still retaining the castaneus mitochondrion."

This assumed that survival was even among the offspring.

However, if hybrids were less fertile, or had a higher mortality rate, then those offspring that were closer to "pure" would survive better and re-separation of the genomes could occur even more rapidly.

"This situation, called mitochondrial capture, would be particularly likely when the original population was small, and when the hybridisation asymmetrical, with males of one subspecies mating with female of the other, but not the other way around," Veale said.

"These are precisely the conditions that would have occurred on boats or in small founding populations in ports."

Previous research had shown how there were severe infertility problems for crosses between mouse subspecies, particularly involving crosses involving male M. m. castaneus.

"Our findings show that in natural populations, the genomes of these two subspecies are so unstable when mixed, and the fertility of hybrids so significantly decreased, that they re-separate over generations, effectively rejecting the DNA of one of them from the population."

The differences in patterns of ancestry "really change how we need to think about how we interpret ancestry based on mitochondrial DNA".

"We got completely different results trying to assess ancestry based on mitochondrial and nuclear DNA, and hence could not have understood the ancestry for New Zealand mice from only mitochondrial data.

"Many studies across the world rely on mitochondrial DNA to look at the history of populations, but our study highlights the need to be careful in interpreting these results."