The genome of even one organism is full of data. A new report, which adds to recent advances in sequencing capability, now reveals the complete genomes of 17 different strains of mice, creating an unmatched genetic catalogue that will help investigations varying from human disease to evolution.

In the September 14 issue of the journal Nature, an international team of investigators, including University of Wisconsin-Madison geneticist Bret Payseur, describe the genome sequencing and comparison of 17 mouse strains, including many of the most frequent laboratory strains and four strains recently copied from wild mice. The database, which is the largest for any vertebrate model organism, records the range of genetic variation between the strains of mice and its effects on phenotypes and gene regulation.

Payseur, an associate professor of medical genetics in the UW-Madison school of Medicine and Public Health explains:

“Mice are the premier model organism for human disease. We’ve made a lot of progress in understanding the genetics of common human diseases by studying mice. Although we’ve been able to map genomic regions that contribute to disease risk, we haven’t known the full spectrum of mutations involved.

The new genetic compendium will help researchers more quickly find the subset of sequence differences responsible for disease and other characters.”

The novel report identifies mutations connected with over 700 biological traits, including diabetes and heart disease.

David Adams from the Wellcome Trust Sanger Institute, who led the project, said:

“We are living in an era where we have thousands of human genome at our fingertips. The mouse, and the genome sequences we have generated, will play a critical role in understanding of how genetic variation contributes to disease and will lead us towards new therapies.”

As well as advancing the use of mice as a model for human disease, Payseur explains that it also advances investigations of evolution, which is his main interest. He asks: ” We were interested in the history of mice – how did mice evolve and come to be such an important organism for research?”

Together with Michael White, they explored the evolutionary history of the laboratory mouse by using sequences from four wild-derived mouse strains, which included 3 common subspecies of house mice and a more distant relative. Together these strains represent a few millions years of evolution, providing the opportunity to look into the processes that drive genetic and phenotypic change.

They discovered that the genomes of the mice did not mirror a single evolutionary story. Instead, different parts of the genome displayed difference patterns of being related. For the 3 wild house mouse subspecies in this investigation, they discovered that almost 40% of the sequence supported one evolutionary relationship, another 30% supported another relationship, and the 30% remaining of the DNA indicated a third relationship.

Payseur says:

“The complexity uncovered here should serve as a cautionary tale for studies of evolutionary relations between organisms, which have often made inferences based on one or a few genes. If you’re looking at closely related species, don’t expect to infer the species history just by looking at a handful of regions. You really have to look at a large fraction of the whole genome.”

Payseur’s aim is to conduct similar examinations of the other sequenced laboratory strains in order to start to fill in the huge gaps which currently exists in lab mouse pedigrees. Understanding the evolution will help provide crucial genetic context for mouse investigations of human diseased and help other investigators decide which strain is the most appropriate for their research questions.

This project was supported by the Medical Research Council, UK., and the Wellcome Trust. Payseur’s study was supported by the U.S. National Science Foundation.

Written by Grace Rattue