title: Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals.
abstract: Gene duplication is a fundamental process in genome evolution. However, most young duplicates are degraded by loss-of-function mutations, and the factors that allow some duplicate pairs to survive long-term remain controversial. One class of models to explain duplicate retention invokes sub- or neofunctionalization, whereas others focus on sharing of gene dosage. RNA-sequencing data from 46 human and 26 mouse tissues indicate that subfunctionalization of expression evolves slowly and is rare among duplicates that arose within the placental mammals, possibly because tandem duplicates are coregulated by shared genomic elements. Instead, consistent with the dosage-sharing hypothesis, most young duplicates are down-regulated to match expression levels of single-copy genes. Thus, dosage sharing of expression allows for the initial survival of mammalian duplicates, followed by slower functional adaptation enabling long-term preservation.
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. xlan@stanford.edu pritch@stanford.edu.
authors.forename: Xun
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA. Department of Biology, Stanford University, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. xlan@stanford.edu pritch@stanford.edu.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Pritchard
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D027963:Chloride-Bicarbonate Antiporters / Q000235:genetics; D019143:Evolution, Molecular; D018628:Gene Dosage; D020440:Gene Duplication; D005786:Gene Expression Regulation; D020131:Genes, Duplicate; D006801:Humans; D051379:Mice; D009154:Mutation; D009928:Organ Specificity / Q000235:genetics; D017423:Sequence Analysis, RNA; D059467:Transcriptome
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D000429:Alcohol Oxidoreductases; C531129:CBR1 protein, human; C531130:CBR3 protein, human