Overlapping protein-coding genes in human genome and their coincidental expression in tissues

Abstract

The completion of human genome sequences and the advancement of next-generation sequencing technologies have engendered a clear understanding of all human genes. Overlapping genes are usually observed in compact genomes, such as those of bacteria and viruses. Notably, overlapping protein-coding genes do exist in human genome sequences. Accordingly, we used the current Ensembl gene annotations to identify overlapping human protein-coding genes. We analysed 19,200 well-annotated protein-coding genes and determined that 4,951 protein-coding genes overlapped with their adjacent genes. Approximately a quarter of all human protein-coding genes were overlapping genes. We observed different clusters of overlapping protein-coding genes, ranging from two genes (paired overlapping genes) to 22 genes. We also divided the paired overlapping protein-coding gene groups into four subtypes. We found that the divergent overlapping gene subtype had a stronger expression association than did the subtypes of 5ʹ-tandem overlapping and 3ʹ-tandem overlapping genes. The majority of paired overlapping genes exhibited comparable coincidental tissue expression profiles; however, a few overlapping gene pairs displayed distinctive tissue expression association patterns. In summary, we have carefully examined the genomic features and distributions about human overlapping protein-coding genes and found coincidental expression in tissues for most overlapping protein-coding genes.

Transcriptome-wide expression profiling of Sporothrix schenckii yeast and mycelial forms and the establishment of the Sporothrix Genome DataBase

“…Interestingly, in our study, we observed different clusters of overlapping cis-SAS genes ranging from 2 (paired overlapping genes) to 14 genes. Similar multigene-transcript overlapping regions have also recently been described in the human genome, where about 72 % of the overlapping protein-encoding genes showed a paired configuration, followed by more complex overlapping groups until reaching 22 overlapping genes in a protocadherin gene cluster on chromosome 5 [49]. Consequently, in terms of gene overlap, our data suggest that the physical chromosomal arrangement of the S. schenckii genes follows, to some extent, the pattern observed in other eukaryotic genomes where the different-strand overlapping type seems to be the most commonly adopted gene model [30].…”

siRNA Mediate RNA Interference Concordant with Early On-Target Transient Transcriptional Interference

“…Together, our findings indicate a role for both TOSPEAK and GDF6 in the joint, bone and cartilage malformations of the SYNS4 family [13]. Given that over 20% of human protein coding genes physically overlap [14] and that many others share promoters, and those like GDF6 that have regulatory elements nested within adjacent genes, the findings of this study have important implications for genotype-phenotype correlation studies and gene targeting strategies and for the design of gene therapies including those that use exogenous siRNA.…”

Overlapping genes in natural and engineered genomes

“…Today, we are seeing a renaissance of the field owing to the rapid advancement of genome-scale protein and RNA measurement tools and increasingly advanced prediction algorithms (Box 1 ), which have collectively revealed an abundance of overlapping genes and ORFs within cellular genomes. Recent work on the human genome has placed estimates of overlapping features much higher than previously thought 8 , 9 , encompassing 26% of all protein-coding genes 10 . This estimate will likely increase in the future as small ORFs (sORFs) encoding microproteins are increasingly being found in the human genome within previously annotated genes 11 – 13 .…”