Evolutionary toggling of the MAPT 17q21.31 inversion region

• Published in: Nature genetics Vol. 40; no. 9; pp. 1076 - 1083
• Main Authors: Zody, Michael C, Jiang, Zhaoshi, Fung, Hon-Chung, Antonacci, Francesca, Hillier, LaDeana W, Cardone, Maria Francesca, Graves, Tina A, Kidd, Jeffrey M, Cheng, Ze, Abouelleil, Amr, Chen, Lin, Wallis, John, Glasscock, Jarret, Wilson, Richard K, Reily, Amy Denise, Duckworth, Jaime, Ventura, Mario, Hardy, John, Warren, Wesley C, Eichler, Evan E
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2008; Nature Publishing Group
• Subjects: Agriculture; Alzheimer's disease; Amyotrophic lateral sclerosis; Animal Genetics and Genomics; Animals; Base Sequence; Biologi; Biological and medical sciences; Biology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Causes of; Cellular proteins; Chromosome Inversion; Chromosomes; Chromosomes, Human, Pair 17; Evolution, Molecular; Evolutionary biology; Fundamental and applied biological sciences. Psychology; Gene Duplication; Gene expression; Gene Function; Gene mutations; Genetic aspects; Genetic diversity; Genetics of eukaryotes. Biological and molecular evolution; Health aspects; Human Genetics; Humans; Inversion (Genetics); Models, Biological; Molecular Sequence Data; Monkeys & apes; NATURAL SCIENCES; NATURVETENSKAP; Pan troglodytes; Pan troglodytes - genetics; Phylogeny; Polymorphism; Polymorphism, Genetic; Pongo pygmaeus - genetics; Primates; Sequence Analysis, DNA; Studies; tau Proteins - genetics; United States; Molecular evolution
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.193

Evan Eichler and colleagues present a sequence assembly of the inverted H2 haplotype of human chromosome 17q21.31 and show that the inversion is polymorphic in other great ape species. Their analyses suggest that the H2 configuration represents the ancestral state in great apes and that inversions have occurred independently in the human and chimpanzee lineages. Using comparative sequencing approaches, we investigated the evolutionary history of the European-enriched 17q21.31 MAPT inversion polymorphism. We present a detailed, BAC-based sequence assembly of the inverted human H2 haplotype and compare it to the sequence structure and genetic variation of the corresponding 1.5-Mb region for the noninverted H1 human haplotype and that of chimpanzee and orangutan. We found that inversion of the MAPT region is similarly polymorphic in other great ape species, and we present evidence that the inversions occurred independently in chimpanzees and humans. In humans, the inversion breakpoints correspond to core duplications with the LRRC37 gene family. Our analysis favors the H2 configuration and sequence haplotype as the likely great ape and human ancestral state, with inversion recurrences during primate evolution. We show that the H2 architecture has evolved more extensive sequence homology, perhaps explaining its tendency to undergo microdeletion associated with mental retardation in European populations.