Creation of artificial karyotypes in mice reveals robustness of genome organization

Dear Editor,

Robertsonian (Rb) fusions contribute to the diversity in species karyotypes. However, how it occurs and propels evolution is still unknown, mainly due to the lack of a simple and efficient method for genetically manipulating chromosomes in animals. While the typical mouse karyotype (2n = 40) is completely telocentric except chromosome Y (ChrY), the western European subspecies M. m. domesticus contains diverse chromosomal races, with a diploid number varying between 38 and 22 due to carrying one or multiple pairs of metacentric chromosomes, which results from the Rb fusions between two telocentric chromosomes.¹ Recapitulation of this process in the laboratory may help to shed light on the function of Rb fusions in evolution. The detailed mechanisms underlying Rb fusion in M. m. domesticus requires further investigations,² but previous studies have shown that Rb fusion-induced metacentric chromosomes have a neo-centromeric region of minor satellite (MinSat) sandwiched between two large blocks of major satellite (MajSat) DNA.³ These observations imply that Rb fusion breakpoints are localized within the MinSat sequences of the centromeric region. Given that CRISPR-Cas9-mediated chromosome engineering has successfully fused 16 yeast chromosomes through head-to-tail strategies to produce yeast strains with 1 or 2 chromosomes,^4,5 we hypothesize that CRISPR-Cas9-mediated chromosome engineering through targeting MinSat sequences could be an ideal strategy for creating mouse strains with reduced chromosome numbers in the laboratory.

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