Inversions and Evolution of the Human Genome

AbstractInversions are a type of naturally occurring DNA mutation in which the sequence of the DNA is reversed, resulting in it being read in the opposite direction to the wild type. Most of these inversion mutations are thought to have no direct phenotypic effect, although those that do are often lethal. Although inversions are mostly phenotypically functionless, inversions cause recombination suppression both within and extending slightly outwards from the inverted region. Recombination suppression between heterozygotic inversions can lead to linkage disequilibrium and cause the independent evolution of chromosomes, eventually leading to speciation. Comparative genomics of humans and primates has identified many inversions which may have contributed to the evolution of the human genome. Population genomics has also identified many inversions which are polymorphic in humans, some of these are under selection and may be contributing to the continued evolution of the human genome.Key ConceptsInversions are naturally occurring mutations within a genome where the DNA has been excised and reinserted in the opposite orientation.Inversions have a range of phenotypic effects including lethality, amino acids changes, regulatory changes or no discernible effect.Alu and L1 elements may have directly caused many inversions in primates through recombination between very similar elements.Inversions suppress recombination within the inverted region and may be involved in evolution and speciation through the recombination‐suppression mechanism.Nine large inversions can be detected cytogenetically when comparing human and chimpanzee genomes, approximately 1500 further microinversions have been identified through sequencing.Polymorphic inversions exist in the human population, some of which have been found to be under positive selection.