Association between divergence and interspersed repeats in mammalian noncoding genomic DNA

The amount of noncoding genomic DNA sequence that aligns between human and mouse varies substantially in different regions of their genomes, and the a mount of repetitive DNA also varies. In this report, we show that divergenc e in noncoding nonrepetitive DNA is strongly correlated with the amount of repetitive DNA in a region. We investigated aligned DNA in four large genom ic regions with finished human sequence and almost or completely finished m ouse sequence. These regions, totaling 5.89 Mb of DNA, are on different chr omosomes and vary in their base composition. An analysis based on sliding w indows of 10 kb shows that the fraction of aligned noncoding nonrepetitive DNA and the fraction of repetitive DNA are negatively correlated, both at t he level of an entire region and locally within it. This conclusion is stro ngly supported by a randomization study, in which repetitive elements are r emoved and randomly relocated along the sequences. Thus, regions of noncodi ng genomic DNA that accumulated fewer point mutations since the primate-rod ent divergence also suffered fewer retrotransposition events. These results indicate that some regions of the genome are more "flexible" over the time scale of mammalian evolution, being able to accommodate many point mutatio ns and insertions, whereas other regions are more "rigid" and accumulate fe wer changes. Stronger conservation is generally interpreted as indicating m ore extensive or more important function. The evidence presented here of co rrelated variation in the rates of different evolutionary processes across noncoding DNA must be considered in assessing such conservation for evidenc e of selection.