Fragile Sites as Drivers of Gene and Genome Evolution

Purpose of Review Although the detailed composition of the human genome is known base by base for its major part, the orchestration of and which elements exactly facilitate organization and flexibility of higher order gene and genome architecture, are poorly understood and scarcely studied. Recent Findings This review focuses on fragile sites (FSs). They are considered as regions of chromosome breakage with overlapping signatures for breakpoints observed repeatedly in tumor and constitutional rearrangements, and also in evolutionary conserved breakpoints. Thus, FSs are promising targets to study and get deeper insights into chromosome, gene, and genome evolution. Summary Here, we summarize the current knowledge on FSs and their correlation with aforementioned breakpoint categories. Based on that, we introduce a new model for FSs driven gene and genome evolution, which also can explain the recently observed spreading of (pseudo-)gene family members among the human genome. FSs therefore may provide an “infrastructure” to distribute gene copies onto different sites of the genome and may be the underlying cause for formation of gene families.