Abundant Raw Material for Cis-Regulatory Evolution in Humans

摘要: Changes in gene expression and regulation--due particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes phenotypes, yet little is known about distribution such variation populations. We present this study first survey experimentally validated functional polymorphism. These data are derived from more than 140 polymorphisms involved regulation 107 genes Homo sapiens, eukaryote species with most available data. find that widespread human genome consequent twofold or greater for 63% surveyed. Transcription factor-DNA interactions highly polymorphic, regulatory have been gained lost within On average, humans heterozygous at sites (>16,000) amino acid positions (<13,000), part because an overrepresentation among former multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role microsatellites may provide a larger store heritable phenotypic rapid mutational input has realized. Finally, we outline distinctive consequences genotype-phenotype relationship, including ubiquitous epistasis genotype-by-environment interactions, as well underappreciated modes pleiotropy overdominance. Ordinary small-scale mutations contribute pervasive transcription rates consequently patterns variation.