Microsatellites in different eukaryotic genomes: survey and analysis.

We examined the abundance of microsatellites with repeated unit lengths of 1-6 base pairs in several eukaryotic taxonomic groups: primates, rodents, other mammals, nonmammalian vertebrates, arthropods, Caenorhabditis elegans, plants, yeast, and other fungi. Distribution of simple sequence repeats was compared between exons, introns, and intergenic regions. Tri- and hexanucleotide repeats prevail in protein-coding exons of all taxa, whereas the dependence of repeat abundance on the length of the repeated unit shows a very different pattern as well as taxon-specific variation in intergenic regions and introns. Although it is known that coding and noncoding regions differ significantly in their microsatellite distribution, in addition we could demonstrate characteristic differences between intergenic regions and introns. We observed striking relative abundance of (CCG)(n)*(CGG)(n) trinucleotide repeats in intergenic regions of all vertebrates, in contrast to the almost complete lack of this motif from introns. Taxon-specific variation could also be detected in the frequency distributions of simple sequence motifs. Our results suggest that strand-slippage theories alone are insufficient to explain microsatellite distribution in the genome as a whole. Other possible factors contributing to the observed divergence are discussed.

[1]  D. Tautz,et al.  Cryptic simplicity in DNA is a major source of genetic variation , 1986, Nature.

[2]  A. Bird CpG-rich islands and the function of DNA methylation , 1986, Nature.

[3]  J. Weber,et al.  Survey of human and rat microsatellites. , 1992, Genomics.

[4]  D. Tautz,et al.  Slippage synthesis of simple sequence DNA. , 1992, Nucleic acids research.

[5]  A. Bird,et al.  Repression of genes by DNA methylation depends on CpG density and promoter strength: evidence for involvement of a methyl‐CpG binding protein. , 1992, The EMBO journal.

[6]  Robert I. Richards,et al.  Dynamic mutations: A new class of mutations causing human disease , 1992, Cell.

[7]  M. Rosbash,et al.  Short artificial hairpins sequester splicing signals and inhibit yeast pre-mRNA splicing , 1993, Molecular and cellular biology.

[8]  D. Nelson,et al.  Trinucleotide repeat expansions in neurological disease , 1993, Current Opinion in Neurobiology.

[9]  L. Andersson,et al.  The abundance of various polymorphic microsatellite motifs differs between plants and vertebrates. , 1993, Nucleic acids research.

[10]  D. Tautz,et al.  Simple sequences. , 1994, Current opinion in genetics & development.

[11]  J T Finch,et al.  Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H. Lehrach,et al.  Trinucleotide repeat expansions and human genetic disease. , 1994, BioEssays : news and reviews in molecular, cellular and developmental biology.

[13]  M. Stratton,et al.  Instability of short tandem repeats (microsatellites) in human cancers , 1994, Nature Genetics.

[14]  S. Rusconi,et al.  Transcriptional activation modulated by homopolymeric glutamine and proline stretches. , 1994, Science.

[15]  Robert I. Richards,et al.  Simple repeat DNA is not replicated simply , 1994, Nature Genetics.

[16]  A. Marquis Gacy,et al.  Trinucleotide repeats that expand in human disease form hairpin structures in vitro , 1995, Cell.

[17]  E. Brody,et al.  An intronic (A/U)GGG repeat enhances the splicing of an alternative intron of the chicken beta-tropomyosin pre-mRNA. , 1995, Nucleic acids research.

[18]  John M. Hancock Simple sequences in a ‘minimal ’ genome , 1996, Nature Genetics.

[19]  John M. Hancock,et al.  Simple sequences and the expanding genome. , 1996, BioEssays : news and reviews in molecular, cellular and developmental biology.

[20]  Graziano Pesole,et al.  CLEANUP: a fast computer program for removing redundancies from nucleotide sequence databases , 1996, Comput. Appl. Biosci..

[21]  C. Wills,et al.  Long, polymorphic microsatellites in simple organisms , 1996, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[22]  R. Lothe,et al.  Microsatellite instability in human solid tumors. , 1997, Molecular medicine today.

[23]  D. Housman,et al.  The complex pathology of trinucleotide repeats. , 1997, Current opinion in cell biology.

[24]  Y. Kashi,et al.  Simple sequence repeats as a source of quantitative genetic variation. , 1997, Trends in genetics : TIG.

[25]  M. Ares,et al.  Intron self-complementarity enforces exon inclusion in a yeast pre-mRNA. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[26]  T. Petes,et al.  Genetic control of microsatellite stability. , 1997, Mutation research.

[27]  A. Razin,et al.  CpG methylation, chromatin structure and gene silencing—a three‐way connection , 1998, The EMBO journal.

[28]  R. Sinden,et al.  Trinucleotide repeat DNA structures: dynamic mutations from dynamic DNA. , 1998, Current opinion in structural biology.

[29]  P. Patel,et al.  The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. , 1998, American journal of human genetics.

[30]  K. Usdin NGG-triplet repeats form similar intrastrand structures: implications for the triplet expansion diseases. , 1998, Nucleic acids research.

[31]  J. R. Roesser,et al.  RNA secondary structure: an important cis-element in rat calcitonin/CGRP pre-messenger RNA splicing. , 1998, Biochemistry.

[32]  R. Wells,et al.  Genetic Instabilities in (CTG·CAG) Repeats Occur by Recombination* , 1999, The Journal of Biological Chemistry.

[33]  Melanie E. Goward,et al.  The DNA sequence of human chromosome 22 , 1999, Nature.

[34]  R. Sinden Biological implications of the DNA structures associated with disease-causing triplet repeats. , 1999, American journal of human genetics.

[35]  S. Warren,et al.  Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells , 1999, Nature Genetics.