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Overlapping genes in the human and mouse genomes.

Sanna CR, Li WH, Zhang L - BMC Genomics (2008)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, Virginia Tech, Blacksburg, USA. csanna@vt.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH
Different scenarios for how two genes A and B may switch from non-overlapping to overlapping, and vice versa. The solid boxes, empty boxes, and empty boxes with arrows are coding exons, 5' UTRs, and 3' UTRs, respectively. Genes A and B are in red and blue, respectively. Cases a-d denote same-strand overlapping genes, while cases e-h denote different-strand overlapping genes. From a non-overlapping state to an overlapping state: (a) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (b) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B within gene A. Unlike case (a), case (b) requires the creation of a new exon, so that it is less likely to occur than case (a). (c) Emergence of a new transcription start site extends the 5' UTR in gene B to partially cover the 3' UTR of gene A. If the extension is long, it may entirely cover gene A. (d) Emergence of a new 5' UTR exon in gene B upstream of gene A results in the embedment of gene A completely inside gene B. (e) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (f) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B inside gene A. (g) Extension of the 5' UTR of gene A in the 5' direction creates a partial overlap of gene A with gene B. (h) Emergence of a new 5' UTR exon in gene A results in the complete embedment of gene B inside gene A. The opposite scenarios to the above would create a transition from the overlapping state to a non-overlapping state of two neighboring genes.
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Figure 4: Different scenarios for how two genes A and B may switch from non-overlapping to overlapping, and vice versa. The solid boxes, empty boxes, and empty boxes with arrows are coding exons, 5' UTRs, and 3' UTRs, respectively. Genes A and B are in red and blue, respectively. Cases a-d denote same-strand overlapping genes, while cases e-h denote different-strand overlapping genes. From a non-overlapping state to an overlapping state: (a) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (b) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B within gene A. Unlike case (a), case (b) requires the creation of a new exon, so that it is less likely to occur than case (a). (c) Emergence of a new transcription start site extends the 5' UTR in gene B to partially cover the 3' UTR of gene A. If the extension is long, it may entirely cover gene A. (d) Emergence of a new 5' UTR exon in gene B upstream of gene A results in the embedment of gene A completely inside gene B. (e) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (f) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B inside gene A. (g) Extension of the 5' UTR of gene A in the 5' direction creates a partial overlap of gene A with gene B. (h) Emergence of a new 5' UTR exon in gene A results in the complete embedment of gene B inside gene A. The opposite scenarios to the above would create a transition from the overlapping state to a non-overlapping state of two neighboring genes.

Mentions: A more likely mechanism for the switch is UTR change, because the majority of the non-conserved overlapping cases are such that the genes that overlap in only one species are located on the same chromosome in the other species. As indicated in Figure 4, for two genes that are neighboring on the same chromosome, the transition between overlapping and non-overlapping states can be simply a matter of gain or loss of either 5' UTR, 3' UTR, or both. For example, a gain of convergent different-strand-overlap genes is fairly simple. The disappearance of a transcription termination site will elongate the RNA transcript and the transcription may run into the 3' of the neighboring gene, so that the two genes become overlap in the 3' end. This may also apply to the case of parallel same-strand neighboring genes, that is, the elongated transcription of an upstream gene may run into the 5' end of the neighboring gene. On the other hand, a gain of divergent different-strand-overlap genes can occur when the transcription start site (TSS) of a gene moves in the 5' direction, so that it includes the TSS of the neighboring gene. Similarly, the loss of convergent different-strand overlaps is simple, namely, the move of a transcription stop site in the 5' direction will shorten the transcription and the overlap may thus disappear. The same comment applies to the case of a parallel overlap.


Overlapping genes in the human and mouse genomes.

Sanna CR, Li WH, Zhang L - BMC Genomics (2008)

Different scenarios for how two genes A and B may switch from non-overlapping to overlapping, and vice versa. The solid boxes, empty boxes, and empty boxes with arrows are coding exons, 5' UTRs, and 3' UTRs, respectively. Genes A and B are in red and blue, respectively. Cases a-d denote same-strand overlapping genes, while cases e-h denote different-strand overlapping genes. From a non-overlapping state to an overlapping state: (a) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (b) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B within gene A. Unlike case (a), case (b) requires the creation of a new exon, so that it is less likely to occur than case (a). (c) Emergence of a new transcription start site extends the 5' UTR in gene B to partially cover the 3' UTR of gene A. If the extension is long, it may entirely cover gene A. (d) Emergence of a new 5' UTR exon in gene B upstream of gene A results in the embedment of gene A completely inside gene B. (e) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (f) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B inside gene A. (g) Extension of the 5' UTR of gene A in the 5' direction creates a partial overlap of gene A with gene B. (h) Emergence of a new 5' UTR exon in gene A results in the complete embedment of gene B inside gene A. The opposite scenarios to the above would create a transition from the overlapping state to a non-overlapping state of two neighboring genes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2335118&req=5

Figure 4: Different scenarios for how two genes A and B may switch from non-overlapping to overlapping, and vice versa. The solid boxes, empty boxes, and empty boxes with arrows are coding exons, 5' UTRs, and 3' UTRs, respectively. Genes A and B are in red and blue, respectively. Cases a-d denote same-strand overlapping genes, while cases e-h denote different-strand overlapping genes. From a non-overlapping state to an overlapping state: (a) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (b) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B within gene A. Unlike case (a), case (b) requires the creation of a new exon, so that it is less likely to occur than case (a). (c) Emergence of a new transcription start site extends the 5' UTR in gene B to partially cover the 3' UTR of gene A. If the extension is long, it may entirely cover gene A. (d) Emergence of a new 5' UTR exon in gene B upstream of gene A results in the embedment of gene A completely inside gene B. (e) Extension of the 3' UTR in gene A due to loss of the transcription stop signal results in extension of gene A into gene B. Here the extension creates only a partial overlap, but a large extension may cover the entire gene B. (f) Emergence of a new 3' UTR exon in gene A results in the complete embedment of gene B inside gene A. (g) Extension of the 5' UTR of gene A in the 5' direction creates a partial overlap of gene A with gene B. (h) Emergence of a new 5' UTR exon in gene A results in the complete embedment of gene B inside gene A. The opposite scenarios to the above would create a transition from the overlapping state to a non-overlapping state of two neighboring genes.
Mentions: A more likely mechanism for the switch is UTR change, because the majority of the non-conserved overlapping cases are such that the genes that overlap in only one species are located on the same chromosome in the other species. As indicated in Figure 4, for two genes that are neighboring on the same chromosome, the transition between overlapping and non-overlapping states can be simply a matter of gain or loss of either 5' UTR, 3' UTR, or both. For example, a gain of convergent different-strand-overlap genes is fairly simple. The disappearance of a transcription termination site will elongate the RNA transcript and the transcription may run into the 3' of the neighboring gene, so that the two genes become overlap in the 3' end. This may also apply to the case of parallel same-strand neighboring genes, that is, the elongated transcription of an upstream gene may run into the 5' end of the neighboring gene. On the other hand, a gain of divergent different-strand-overlap genes can occur when the transcription start site (TSS) of a gene moves in the 5' direction, so that it includes the TSS of the neighboring gene. Similarly, the loss of convergent different-strand overlaps is simple, namely, the move of a transcription stop site in the 5' direction will shorten the transcription and the overlap may thus disappear. The same comment applies to the case of a parallel overlap.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Computer Science, Virginia Tech, Blacksburg, USA. csanna@vt.edu

ABSTRACT

Background: 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.

Results: 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.

Conclusion: 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.

Show MeSH