Abundance and length of simple repeats in vertebrate genomes are determined by their structural properties

作者：Bacolla Albino^*; Larson Jacquelynn E; Collins Jack R; Li Jian; Milosavljevic Aleksandar; Stenson Peter D; Cooper David N; Wells Robert D

来源：Genome Research, 2008, 18(10): 1545-1553.

DOI：10.1101/gr.078303.108

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 >= 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.

• 出版日期2008-10
• 单位河北医科大学