A unique set of mouse outbred lines has been generated through selective breeding in the longest selection experiment ever conducted on mice. Over the course of >140 generations, selection on the control line has given rise to two extremely fertile lines (>20 pups per litter each), two giant growth lines (one lean, one obese) and one long-distance running line.
Genomic analysis revealed line-specific patterns of genetic variation among lines and high levels of homozygosity within lines as a result of long-term intensive selection, genetic drift and isolation. Detection of line-specific patterns of genetic differentiation and structural variation revealed multiple candidate genes behind the improvement of the selected traits.
We conclude that the genomes of these lines are rich in beneficial alleles for the respective selected traits and represent an invaluable resource for unraveling the polygenic basis of fertility, obesity, muscle growth and endurance fitness.
…The worldwide longest selection experiment on mice began in the early 1970’s at the former Forschungszentrum für Tierproduktion (FZT), nowadays called Leibniz Institute for Farm Animal Biology (FBN) located in Dummerstorf, Germany4,5. Starting from a single founder line, selection lines for different complex traits were bred with population sizes of 60–100 breeding pairs per line. An unselected control line from the same founder line was maintained over the entire selection period with a larger population size (125–200 breeding pairs)4,5. Over the course of >140 generations, selection has shaped the genomes of the Dummerstorf trait-selected mouse lines, leading to extreme phenotypes that include increased litter size (more than double the litter size of the unselected mouse line)6, body mass (approx. 90g body weight at 6 weeks of age)7 and endurance (up to 3× higher untrained running capacity)8
…Phenotypic impact of selection: Over the course of more than 140 generations, the selected traits have shown remarkable increments in each line (Figure 1). The span and number of generations makes the present study the longest selection experiment ever reported in mice. Relative to the unselected control line FZTDU (exposed to genetic drift only), reproductive performance has doubled in DUK and DUC (Figure 1A–B, F–G). Even though these 2 trait-selected lines have achieved comparable litter sizes at first delivery (>20 offspring)58, their reproductive lifespan differs, with 5.8 and 2.7 litters in average per lifetime for DUK and DUC, respectively58. A remarkable level of divergence has been achieved by the increased body size lines (Figure 1C–D). DU6 individuals have almost tripled their weight compared to FZTDU (Figure 1H), whereas mice of the protein line DU6P not only have become larger and heavier than FZTDU mice, but their level of muscularity is also considerably higher (Figure 1D, 1I). In terms of running distance capacity, DUhLB mice can on average cover distances 3× as long as those covered by FZTDU (Figure 1J). With the exception of the obese line DU659, each one of the trait-selected mouse lines has developed an extreme phenotype without obvious detrimental effects on their general health, well-being and longevity.
