title: Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties.
abstract: Microsatellites are abundant in vertebrate genomes, but their sequence representation and length distributions vary greatly within each family of repeats (e.g., tetranucleotides). Biophysical studies of 82 synthetic single-stranded oligonucleotides comprising all tetra- and trinucleotide repeats revealed an inverse correlation between the stability of folded-back hairpin and quadruplex structures and the sequence representation for repeats > or =30 bp in length in nine vertebrate genomes. Alternatively, the predicted energies of base-stacking interactions correlated directly with the longest length distributions in vertebrate genomes. Genome-wide analyses indicated that unstable sequences, such as CAG:CTG and CCG:CGG, were over-represented in coding regions and that micro/minisatellites were recruited in genes involved in transcription and signaling pathways, particularly in the nervous system. Microsatellite instability (MSI) is a hallmark of cancer, and length polymorphism within genes can confer susceptibility to inherited disease. Sequences that manifest the highest MSI values also displayed the strongest base-stacking interactions; analyses of 62 tri- and tetranucleotide repeat-containing genes associated with human genetic disease revealed enrichments similar to those noted for micro/minisatellite-containing genes. We conclude that DNA structure and base-stacking determined the number and length distributions of microsatellite repeats in vertebrate genomes over evolutionary time and that micro/minisatellites have been recruited to participate in both gene and protein function.
authors.affiliation: Institute of Biosciences and Technology, Center for Genome Research, Texas A&M University Health Science Center, Houston, Texas 77030, USA. abacolla@ibt.tamhsc.edu
authors.forename: Albino
authors.initials: A
authors.lastname: Bacolla
authors.forename: Jacquelynn E
authors.initials: JE
authors.lastname: Larson
authors.forename: Jack R
authors.initials: JR
authors.lastname: Collins
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Milosavljevic
authors.forename: Peter D
authors.initials: PD
authors.lastname: Stenson
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Robert D
authors.initials: RD
authors.lastname: Wells
mesh_terms: D000818:Animals; D020029:Base Pairing; D004247:DNA / Q000737:chemistry*; D030561:Databases, Nucleic Acid; D016678:Genome; D006801:Humans; D018895:Microsatellite Repeats; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D013696:Temperature; D018911:Trinucleotide Repeats
chemical_list: D004247:DNA