Fragile Sites in Human and Macaca Fascicularis Chromosomes are Breakpoints in Chromosome Evolution

Abstract

We have analysed the expression of aphidicolin-induced common fragile sites at two different aphidicolin concentrations (0.1 µmol/L and 0.2 µmol/L) in three female and one male crab-eating macaques (Macaca fascicularis, Cercopithecidae, Catarrhini). A total of 3948 metaphases were analysed: 1754 in cultures exposed to 0.1 µmol/L aphidicolin, 1261 in cultures exposed to 0.2 µmol/L aphidicolin and 933 in controls. The number of breaks and gaps detected ranged from 439 in cultures exposed to 0.1 µmol/L aphidicolin to 2061 in cultures exposed to 0.2 µmol/L aphidicolin. The use of a multinomial FSM statistical model allowed us to identify 95 fragile sites in the chromosomes of M. fascicularis, of which only 16 are expressed in all four specimens. A comparative study between the chromosomes of M. fascicularis and man has demonstrated that 38 human common fragile sites (50%) are found in the equivalent location in M. fascicularis. The analysis of the rearrangements that have taken place during chromosome evolution has revealed that the breakpoints involved in these rearrangements correspond significantly (p < 0.025) to the location of M. fascicularis fragile sites.