Transposon-free regions in mammalian genomes

Abstract

Despite the presence of over 3 million transposons separated on average by approximately 500 bp, the human and mouse genomes each contain almost 1000 transposon-free regions (TFRs) over 10 kb in length. The majority of human TFRs correlate with orthologous TFRs in the mouse, despite the fact that most transposons are lineage specific. Many human TFRs also overlap with orthologous TFRs in the marsupial opossum, indicating that these regions have remained refractory to transposon insertion for long evolutionary periods. Over 90% of the bases covered by TFRs are noncoding, much of which is not highly conserved. Most TFRs are not associated with unusual nucleotide composition, but are significantly associated with genes encoding developmental regulators, suggesting that they represent extended regions of regulatory information that are largely unable to tolerate insertions, a conclusion difficult to reconcile with current conceptions of gene regulation.

Figure 1.

Transposon-free regions surrounding the NR2F1 gene or its closest homolog in six amniote species. Each panel shows a modified screenshot displaying a 90-kb genomic region from the UCSC Genome Browser (http://genome.ucsc.edu/). Horizontal red bars indicate TFRs, the NR2F1 gene is in blue, brown ticks indicate transposons, black bars in the Gaps track indicate gaps in the genome assembly, and dashed red boxes highlight large regions free of annotated transposons. (A) Human (chr5:92,910–93,000 kb, May 2004). (B) Mouse (chr13:74,743–74,833 kb, May 2004) showing five TFRs ≥ 5 kb (separated by one SINE and several small assembly gaps). (C) Rat (chr2:5,757–5,847 kb, June 2003). (D) Dog (chr3:18,489–18,569 kb, July 2004). The NR2F1 homolog is the closest match to the human mRNA (Non-Dog RefSeq Genes track). (E) Opossum (scaffold_19227:2,391–2,481 kb, October 2004). The NR2F1 homolog is the closest match to the human NR2F1 protein (Human Proteins track). (F) Chicken (chrW:2,350–2,440 kb, February 2004). The NR2F1 homolog is the closest match to the human mRNA (Non-Chicken RefSeq Genes track).

Figure 2.

Breakdown of nucleotide annotations of 12.2 Mb of human TFRs. The pie chart illustrates the fraction of TFR bases that are annotated by the UCSC Known Genes track (Karolchik et al. 2003) as protein coding (coding), 5′ and 3′-untranslated regions (UTR), intronic and intergenic regions.