Overlapping genes in the human and mouse genomes

Department of Computer Science, Virginia Tech, Blacksburg, USA.
BMC Genomics (Impact Factor: 4.04). 02/2008; 9(1):169. DOI: 10.1186/1471-2164-9-169
Source: PubMed

ABSTRACT Increasing evidence suggests that overlapping genes are much more common in eukaryotic genomes than previously thought. In this study we identified and characterized the overlapping genes in a set of 13,484 pairs of human-mouse orthologous genes.
About 10% of the genes under study are overlapping genes, the majority of which are different-strand overlaps. The majority of the same-strand overlaps are embedded forms, whereas most different-strand overlaps are not embedded and in the convergent transcription orientation. Most of the same-strand overlapping gene pairs show at least a tenfold difference in length, much larger than the length difference between non-overlapping neighboring gene pairs. The length difference between the two different-strand overlapping genes is less dramatic. Over 27% of the different-strand-overlap relationships are shared between human and mouse, compared to only approximately 8% conservation for same-strand-overlap relationships. More than 96% of the same-strand and different-strand overlaps that are not shared between human and mouse have both genes located on the same chromosomes in the species that does not show the overlap. We examined the causes of transition between the overlapping and non-overlapping states in the two species and found that 3' UTR change plays an important role in the transition.
Our study contributes to the understanding of the evolutionary transition between overlapping genes and non-overlapping genes and demonstrates the high rates of evolutionary changes in the un-translated regions.

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    • "That may be a reason why gene-overlap events go on and off during the evolutionary course, such as the overlap of MINK1 and CHRNE [44]. Importantly, most overlapping genes are new or lineage-specific [9] [10] [11], and nested ones are further reported as tissue-specific genes [37]. These all address the need and significance of investigating overlapping genes. "
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    ABSTRACT: Overlapping genes are pairs of adjacent genes whose genomic regions partially overlap. They are notable by their potential intricate regulation, such as cis-regulation of nested gene-promoter configurations, and post-transcriptional regulation of natural antisense transcripts. The originations and consequent detailed regulation remain obscure. Herein, we propose a unified framework comprising biological classification rules followed by extensive analyses, namely, exon-sharing analysis, a human-mouse conservation study, and transcriptome analysis of hundreds of microarrays and transcriptome sequencing data (mRNA-Seq). We demonstrate that the tail-to-tail architecture would result from sharing functional elements in 3'-untranslated regions (3'-UTRs) of pre-existing genes. Dissimilarly, we illustrate that the other gene overlaps would originate from a new gene arising in a pre-existing gene locus. Interestingly, these types of coupled overlapping genes may influence each other synergistically or competitively during transcription, depending on the promoter configurations. This framework discloses distinctive characteristics of overlapping genes to be a foundation for a further comprehensive understanding of them.
    Genomics 07/2012; 100(4):231-9. DOI:10.1016/j.ygeno.2012.06.011 · 2.79 Impact Factor
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    • "Under such circumstances, gene viability and evolution are possible. In the absence of any of these conditions, most overlaps of functionally relevant genes will be eliminated by purifying selection; however, as previously demonstrated (Sanna et al. 2008; Shintani et al. 1999), overlapping genes often exploit the 3 0 and 5 "
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    Human Genetics 07/2011; 131(2):265-74. DOI:10.1007/s00439-011-1075-9 · 4.52 Impact Factor
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    • "ee poly - morphisms in the putative 3¢ - UTR of DEAF1 are of partic - ular interest . Polyadenylation signal prediction indicates a considerable overlap of the 3¢UTRs of DRD4 and DEAF1 . Thus , there is the intriguing possibility that the transcripts from opposite strands interact at their 3¢ ends in a sense – antisense manner ( Sun et al . 2005 ; Sanna et al . 2008 ) . The extent of such an interaction could depend on structural differences of the RNA molecules that could be conferred by the polymorphisms . This could affect the translation of one or both genes . Thus , functional studies should be focused on SNPs located in the 3¢ - UTRs of both genes . Analysing the functional consequences of th"
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