The functional and evolutionary significance of nested genes. Grace Y C Lee¹, Hsiao-Han Chang². 1) Ecology and Evolution, University of Chicago, Chicago, IL; 2) Organismic and Evolutionary Biology, Harvard University, Cambridge, MA.

   The distribution of genes in the genome is not random: there are gene deserts with few functional genes as well as genomic regions where genes are densely packed and partially or entirely overlap. An especially interesting class of overlapping genes is in which one gene is completely nested within an intron of another gene (nested and including gene, respectively). Even though the coding sequences of these nested/including gene pairs do not overlap, their intimate structures and the possibility of shared regulatory sequences raise questions about the evolutionary forces governing the origination of nested genes and their subsequent functional and evolutionary impacts. We found ~7% of genes in the Drosophila melanogaster genome are in nested gene structure. Nested genes tend to be more recently derived, under less evolutionary constraint, and more narrowly expressed than other genes, while including genes show the opposite patterns. Surprisingly, expression levels of nested/including gene pairs are less likely to be positively correlated than the expression levels of randomly selected pairs of adjacent yet non-overlapping genes. Interestingly, there are significantly more nested genes in trans orientation to their including genes than are in cis orientation. We hypothesized that this is due to selection against potential erroneous mRNA splicing when nested/including gene pairs are in cis orientation. Consistent with this hypothesis, we found that cis-nested genes are more likely to have only one exon and to have stronger tissue-specific expression than trans-nested genes, while there is no obvious difference between cis- and trans- including genes. Also, transposable elements that are trans-nested in introns are enriched in the reference genome and occur at higher population frequencies than cis-nested transposable elements.