LAUSR

Significance The phenomenon of retroposition (the reintegration of reverse-transcribed RNA into the genome) has been well studied in comparisons between species and has been identified as a source of evolutionary innovation. However, less attention has been paid to possible negative effects of retroposition. To trace the evolutionary dynamics of these negative effects, our study uses a unique genomic dataset of house mouse populations. It reveals that the initial retroposition rate is very high and that most of these newly transposed retrocopies have a deleterious impact, apparently through modifying the expression of their parental genes. In humans, this effect is expected to cause disease alleles, and we propose that genetic screening should include the search for newly transposed retrocopies. Gene retroposition is known to contribute to patterns of gene evolution and adaptations. However, possible negative effects of gene retroposition remain largely unexplored since most previous studies have focused on between-species comparisons where negatively selected copies are mostly not observed, as they are quickly lost from populations. Here, we show for natural house mouse populations that the primary rate of retroposition is orders of magnitude higher than the long-term rate. Comparisons with single-nucleotide polymorphism distribution patterns in the same populations show that most retroposition events are deleterious. Transcriptomic profiling analysis shows that new retroposed copies become easily subject to transcription and have an influence on the expression levels of their parental genes, especially when transcribed in the antisense direction. Our results imply that the impact of retroposition on the mutational load has been highly underestimated in natural populations. This has additional implications for strategies of disease allele detection in humans.