Segmental Duplications: A Source of Diversity, Evolution and Disease

Abstract

Abstract Genome mutations represent a source of variability on which selective pressure acts: negative changes are purged from the populations, whereas positive and neutral changes may be fixed. Segmental duplications ( SDs ) in the human genome trigger mutations such as structural rearrangements (duplications, deletions, inversions and translocations), thus playing a crucial role in human disease and genome evolution. Several human diseases (genomic disorders) are caused by non‐allelic homologous recombination ( NAHR ) between highly similar SDs , as well as gene‐containing SDs were crucial to survival and adaptation of human species during evolution. Moreover, both from a pathological and an evolutionary point of view, SDs represent critically important regions for acentric fragment rescue during neocentromerization process. In this light, disease and evolution can be considered as ‘two sides of the same coin’, where the coin represents the SD ‐mediated chromosomal rearrangements. Key Concepts Segmental duplications (SDs) create variability in human genome. Mediating non‐allelic homologous recombination (NAHR) segmental duplications mediate chromosomal unbalance. Duplicated genes may show pattern of expression different from ancestral gene. Segmental duplications are the remains of ancestral pericentromeric regions. Neocentromere can generate at loci where ancestral centromere were located.