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BMC Genomics
2007 May 16;8:470. doi: 10.1186/1471-2164-8-470.
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Maintenance of transposon-free regions throughout vertebrate evolution.
Simons C
,
Makunin IV
,
Pheasant M
,
Mattick JS
.
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We recently reported the existence of large numbers of regions up to 80 kb long that lack transposon insertions in the human, mouse and opossum genomes. These regions are significantly associated with loci involved in developmental and transcriptional regulation. Here we report that transposon-free regions (TFRs) are prominent genomic features of amphibian and fish lineages, and that many have been maintained throughout vertebrate evolution, although most transposon-derived sequences have entered these lineages after their divergence. The zebrafish genome contains 470 TFRs over 10 kb and a further 3,951 TFRs over 5 kb, which is comparable to the number identified in mammals. Two thirds of zebrafish TFRs over 10 kb are orthologous to TFRs in at least one mammal, and many have orthologous TFRs in all three mammalian genomes as well as in the genome of Xenopus tropicalis. This indicates that the mechanism responsible for the maintenance of TFRs has been active at these loci for over 450 million years. However, the majority of TFR bases cannot be aligned between distantly related species, demonstrating that TFRs are not the by-product of strong primary sequence conservation. Syntenically conserved TFRs are also more enriched for regulatory genes compared to lineage-specific TFRs. We suggest that TFRs contain extended regulatory sequences that contribute to the precise expression of genes central to early vertebrate development, and can be used as predictors of important regulatory regions.
Figure 1. Summary of the number of zebrafish TFRs that are orthologous to TFRs in three mammalian species. (A) Proportions of zebrafish TFRs that have an orthologous TFR in three, two or one mammal species. The bar on the left relates to zebrafish TFRs ≥ 10 kb with orthologous mammalian TFRs ≥ 10 kb. The center bar relates to zebrafish TFRs ≥ 10 kb with orthologous mammalian TFRs ≥ 5 kb. The bar on the right relates to zebrafish TFRs ≥ 5 kb with orthologous mammalian TFRs ≥ 5 kb. (B) Venn diagram of zebrafish TFRs ≥ 10 kb with orthologs ≥ 10 kb in one or more mammal species. The numbers on the graph represent the count of zebrafish TFRs in each category.
Figure 2. Orthologous human and zebrafish TFRs that contain the miRNA mir-129-2. (A) 20 kb of the human genome (chr11:43,548,001–43,568,000) including the non-genic 13 kb TFR hs11.145 (red bar). Thick blue bars indicate blocks of sequence that are alignable to the orthologous zebrafish TFR dr25.92. Small purple bar indicates the position of the human miRNA mir-129-2. (B) A close up view of 130 bp around mir-129-2, thick purple bar indicates the mature miRNA, thin purple line indicates pre-miRNA hairpin. Blue conservation plot is based on the alignment of 17 vertebrate species and green plot based on pairwise alignment of human and zebrafish that shows a conservation profile consistent with the presence of a miRNA conserved in each species [38]. (C) Syntenic region of the zebrafish genome (20 kb chr25:31,421,001–31,441,000) including the TFR dr25.92. Thick blue bars indicate blocks of sequence that are alignable to the orthologous human TFR hs11.145. Although there are currently no genes annotated in this region, the conservation profile suggests that an ortholog of mir-129-2 resides within the TFR. All images are modified screen shots taken from the UCSC genome browser [31].
Figure 3. Comparison of the GC content of TFRs in zebrafish and human. (A) Histogram of the GC content of zebrafish TFRs. Area indicated in blue describes the subset of TFRs that have an orthologous TFR in human larger than 10 kb, the area in red have an orthologous TFR in human larger than 5 kb. (B) Histogram of the GC content of human TFRs. Area indicated in blue describes the subset of TFRs that have an orthologous TFR in zebrafish larger than 10 kb, the area in red have an orthologous TFR in zebrafish larger than 5 kb. (C) Scatter plot of the GC content of orthologous pairs of zebrafish and human TFRs ≥ 10 kb in both species. Points in red indicate TFR pairs with a difference of absolute GC% greater than 20.
Figure 4. Zebrafish transposon-free region dr3.89 and the orthologous regions of four vertebrate species. Each panel shows a modified screenshot displaying a 60 kb region from the UCSC genome browser. Horizontal red bars indicate TFRs and brown ticks indicate transposons. (A) Zebrafish (chr3:24,391-24,451 kb, March 2006) including the 25.9 kb TFR dr3.89. Human proteins mapped to the zebrafish genome by chained tBLASTn are indicated in blue. (B) Human (chr7:23,450-23,510 kb, March 2006) including the 13.7 kb TFR hs7.101. Human RefSeq genes are indicated in blue. (C) Mouse (chr6:49,114-49,174 kb, February 2006) including the 9.3 kb TFR mm6.309. Mouse RefSeq genes are indicated in blue. (D) Opossum (chr8:296,183-296,243 kb, January 2006) including the 16.4 kb TFR md8.376. Human RefSeq genes mapped to the opossum genome with BLAT are indicated in blue. (E) Frog (scaffold_56:3,208-3,268 kb, August 2005) including a 14 kb region that contains no transposons (red box). Human proteins mapped to the frog genome with tBLASTn are indicated in blue.
Arkhipova,
Mobile genetic elements and sexual reproduction.
2005, Pubmed
Arkhipova,
Mobile genetic elements and sexual reproduction.
2005,
Pubmed
Arnaud,
SINE retroposons can be used in vivo as nucleation centers for de novo methylation.
2000,
Pubmed
Bernstein,
Genomic maps and comparative analysis of histone modifications in human and mouse.
2005,
Pubmed
Bernstein,
A bivalent chromatin structure marks key developmental genes in embryonic stem cells.
2006,
Pubmed
Camon,
The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology.
2004,
Pubmed
Curcio,
The outs and ins of transposition: from mu to kangaroo.
2003,
Pubmed
Druker,
Retrotransposon-derived elements in the mammalian genome: a potential source of disease.
2004,
Pubmed
Fisher,
Conservation of RET regulatory function from human to zebrafish without sequence similarity.
2006,
Pubmed
Harris,
The Gene Ontology (GO) database and informatics resource.
2004,
Pubmed
Häsler,
Alu elements as regulators of gene expression.
2006,
Pubmed
Hubbard,
Ensembl 2007.
2007,
Pubmed
Huntsman,
MLL2, the second human homolog of the Drosophila trithorax gene, maps to 19q13.1 and is amplified in solid tumor cell lines.
1999,
Pubmed
Jurka,
Repbase Update, a database of eukaryotic repetitive elements.
2005,
Pubmed
Karolchik,
The UCSC Genome Browser Database.
2003,
Pubmed
Kent,
Evolution's cauldron: duplication, deletion, and rearrangement in the mouse and human genomes.
2003,
Pubmed
Lander,
Initial sequencing and analysis of the human genome.
2001,
Pubmed
Leib-Mösch,
Evolution and biological significance of human retroelements.
1995,
Pubmed
Lev-Maor,
RNA-editing-mediated exon evolution.
2007,
Pubmed
Lippman,
Role of transposable elements in heterochromatin and epigenetic control.
2004,
Pubmed
Lowe,
Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.
2007,
Pubmed
Martens,
The profile of repeat-associated histone lysine methylation states in the mouse epigenome.
2005,
Pubmed
Mikkelsen,
Genome of the marsupial Monodelphis domestica reveals innovation in non-coding sequences.
2007,
Pubmed
Milenkovic,
Mouse patched1 controls body size determination and limb patterning.
1999,
Pubmed
Santos,
Epigenetic reprogramming during early development in mammals.
2004,
Pubmed
Siepel,
Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
2005,
Pubmed
Simons,
Transposon-free regions in mammalian genomes.
2006,
Pubmed
Sironi,
Analysis of intronic conserved elements indicates that functional complexity might represent a major source of negative selection on non-coding sequences.
2005,
Pubmed
Sironi,
Gene function and expression level influence the insertion/fixation dynamics of distinct transposon families in mammalian introns.
2006,
Pubmed
Vandepoele,
Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray-finned fishes and land vertebrates.
2004,
Pubmed
Walter,
Repetitive elements in imprinted genes.
2006,
Pubmed
Waterston,
Initial sequencing and comparative analysis of the mouse genome.
2002,
Pubmed
Woodburne,
The evolution of tribospheny and the antiquity of mammalian clades.
2003,
Pubmed
