title: Structure and evolution of the filaggrin gene repeated region in primates.
abstract: The evolutionary dynamics of repeat sequences is quite complex, with some duplicates never having differentiated from each other. Two models can explain the complex evolutionary process for repeated genes-concerted and birth-and-death, of which the latter is driven by duplications maintained by selection. Copy number variations caused by random duplications and losses in repeat regions may modulate molecular pathways and therefore affect phenotypic characteristics in a population, resulting in individuals that are able to adapt to new environments. In this study, we investigated the filaggrin gene (FLG), which codes for filaggrin-an important component of the outer layers of mammalian skin-and contains tandem repeats that exhibit copy number variation between and within species. To examine which model best fits the evolutionary pathway for the complete tandem repeats within a single exon of FLG, we determined the repeat sequences in crab-eating macaque (Macaca fascicularis), orangutan (Pongo abelii), gorilla (Gorilla gorilla), and chimpanzee (Pan troglodytes) and compared these with the sequence in human (Homo sapiens).
  
  
  
  In this study we compared concerted and birth-and-death evolution models, commonly used for gene copies. We found that there is high nucleotide diversity between filaggrin repeat regions, which fits the birth-and-death model. Phylogenetic analyses also suggested that independent duplication events created the repeat sequences in crab-eating macaques and orangutans, while different duplication and loss events created the repeats in gorillas, chimpanzees, and humans. Comparison of the repeat sequences detected purifying selection within species and lineage-specific duplications across species. We also found variation in the length of the repeated region within species such as chimpanzee and crab-eating macaque.
  
  
  
  We conclude that the copy number variation in the repeat sequences of FLG between primates may be a consequence of species-specific divergence and expansion.
authors.affiliation: Department of Genetics, School of Life Sciences, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan.|Division of Human Genetics, National Institute of Genetics, Mishima, 411-8540, Japan.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Romero
authors.affiliation: Division of Human Genetics, National Institute of Genetics, Mishima, 411-8540, Japan.|Present address: Department of Bioinformatics and Genomics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, 920-8640, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hosomichi
authors.affiliation: Department of Genetics, School of Life Sciences, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan.|Division of Human Genetics, National Institute of Genetics, Mishima, 411-8540, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakaoka
authors.affiliation: Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, 812-8582, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shibata
authors.affiliation: Department of Genetics, School of Life Sciences, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan. itinoue@nig.ac.jp.|Division of Human Genetics, National Institute of Genetics, Mishima, 411-8540, Japan. itinoue@nig.ac.jp.
authors.forename: Ituro
authors.initials: I
authors.lastname: Inoue
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics; D000818:Animals; D005075:Biological Evolution; D056915:DNA Copy Number Variations; D019143:Evolution, Molecular; D000091344:Filaggrin Proteins; D020440:Gene Duplication; D006801:Humans; D007381:Intermediate Filament Proteins / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011323:Primates / Q000235:genetics*; D016415:Sequence Alignment; D013045:Species Specificity
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins
keywords: Birth-and-death evolution; Copy number variation; Duplication/loss; Filaggrin