Overlapping genetic information in eukaryotes

Question

In my research, I look at a lot of gene predictions / annotations. Frequently, I see loci where multiple gene models overlap. I haven't taken a systematic approach to analyzing these cases, but I do remember seeing quite a bit of variation in the direction of the overlapping genes (same vs different directions), the amount of overlap, and even the number of overlapping genes.

I know enough about gene prediction to take any computational predictions with a grain of salt--even those supported by transcript and peptide alignments. However, these cases have me thinking--does overlap of genetic information really occur in eukaryotes? I seem to remember learning (or hearing anecdotally) that it can happen in prokaryotes, and that seems to be understandable given the compactness of prokaryotic genomes. But can this happen in eukaryotes? Has this been studied, and are there cases that have been confirmed experimentally?

Answer 1

You might be interested in the INK4A locus (chromosome 9p), encoding both p19 and p16 genes, very close to p15. You can read a description here. All three proteins are known experimentally to exist.

Now, whether these are two different genes or the same gene with alternative splicing and start sites leading to different reading frames it's up to discussion. The point is that p19 and p16 share DNA coding sequence but not protein sequence nor function.

Answer 2

In general, the compactnes of genomes is a characteristic of prokaryotes, but there are several eykaryotes that have overlapping genes: many parasites and endosymbionts. The best studied of these are the fungal parasites of the phylum microsporidia and the nucleomorphs (remnant nuclei of algal endosymbionts in cryptophytes and chlorarachniophytes).

cDNA library was constructed from the microsporidian Antonospora locustae and 1,146 cDNA clones were sequenced. Here is part of the expression profile (1):

Of the 871 clones found to encode recognizable genes, 97 transcripts (11%) from 70 distinct loci encoded sequence from more than one gene (Fig. 1 A ; see also Table 1, which is published as supporting information on the PNAS web site). The polyA sites of these clones do not correspond to polyA tracts in the genome, so they are unlikely to derive from DNA contamination (see also below), but instead come from polyA RNA. In prokaryotes, polycistronic mRNAs commonly code for multiple proteins (11), but with few exceptions (12) eukaryotic mRNAs encode a single gene. A. locustae multigene transcripts encode two or three genes or gene fragments in various orientations (Fig. 1 B–I ), but they cannot all be polycistronic messages because there is no bias for genes being on the same strand.

Here is part of a review paper on the nucleomorphs genome (2):

As in other reduced genomes, the G. theta nucleomorph genome possesses a very high A+T content (75%) and gene density is extremely high: 1 gene per 977 bp and 44 genes overlap by as many as 76 nucleotides. Williams et al. (84) showed that transcription of the G. theta nucleomorph genome is affected by this compaction, with nucleomorph-derived messenger RNAs often possessing coding sequence for more than one gene, albeit with no strand bias. It appears that during the process of genome compaction, transcription regulatory elements (e.g., promoters, terminators) have moved from the intergenic spacers into the coding regions themselves (84).

I also have to point out that there are a few examples of overlapping genes in yeast: CCT6 overlaps with YDR187C and CCT8 overlaps with YJL009W (3).

1. A high frequency of overlapping gene expression in compacted eukaryotic genomes
2. Nucleomorph Genomes, Annual Review of Genetics
3. The Chemical Genomic Portrait of Yeast: Uncovering a Phenotype for All Genes