Microhomology-Mediated Intron Loss during Metazoan Evolution

How introns are lost from eukaryotic genomes during evolution remains an enigmatic question in biology. By comparative genome analysis of five Caenorhabditis and eight Drosophila species, we found that the likelihood of intron loss is highly influenced by the degree of sequence homology at exon–intron junctions: a significant elevated degree of microhomology was observed for sequences immediately flanking those introns that were eliminated from the genome of one or more subspecies. This determinant was significant even at individual nucleotides. We propose that microhomology-mediated DNA repair underlies this phenomenon, which we termed microhomology-mediated intron loss. This hypothesis is further supported by the observations that in both species 1) smaller introns are preferentially lost over longer ones and 2) genes that are highly transcribed in germ cells, and are thus more prone to DNA double strand breaks, display elevated frequencies of intron loss. Our data also testify against a prominent role for reverse transcriptase-mediated intron loss in metazoans.