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Diverse splicing patterns of exonized Alu elements in human tissues.

Lin L, Shen S, Tye A, Cai JJ, Jiang P, Davidson BL, Xing Y - PLoS Genet. (2008)

Bottom Line: Most of such exons are derived from ancient Alu elements in the genome.Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees.Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

ABSTRACT
Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

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Related in: MedlinePlus

Most Alu exons with substantial transcript inclusion levels are derived from ancient Alu elements in the human genome.Plotted here are distributions of AluJ Class and AluS Class in the human genome, in Alu-derived internal exons, and in Alu-derived exons with substantial transcript inclusion levels based on our RT-PCR results. AluJ class is indicated by white column; AluS class is indicated by hatched column.
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pgen-1000225-g004: Most Alu exons with substantial transcript inclusion levels are derived from ancient Alu elements in the human genome.Plotted here are distributions of AluJ Class and AluS Class in the human genome, in Alu-derived internal exons, and in Alu-derived exons with substantial transcript inclusion levels based on our RT-PCR results. AluJ class is indicated by white column; AluS class is indicated by hatched column.

Mentions: In this study, we conducted RT-PCR analysis of 38 Alu-derived exons in 10 human tissues. 26 of the 38 exons had at least medium inclusion levels in certain tissues. These exons are in genes from a wide range of functional categories (see the complete list in Table S2). Analyses of these 26 exons revealed several interesting characteristics. 23 of the 26 exons were derived from the antisense strand of Alu elements, among which 14 were from the right arm of the antisense Alu (see Figure S5), consistent with a recent report that the right arm of Alu antisense strand is a hotspot for exonization [53]. Moreover, of these 26 exons, 23 were from AluJ class and 3 were from the AluS class. By contrast, in the total set of Alu-derived exons in our study, 211 were from AluJ and 111 were from AluS, a 4-fold shift in the ratio of AluJ to AluS (7.7 in the “substantially included” set versus 1.9 in the total set; P = 0.01, one-tailed Fisher exact test). In the human genome, AluJ is outnumbered by AluS at a ratio of 1 to 2.3 [14] (Figure 4). The similar trend was also found in the 19 “correlated” exons; 16 were from the AluJ class and 3 were from the AluS class. Taken together, these data are consistent with the fact that AluJ is the oldest Alu subclass in the human genome [54], so that exons derived from AluJ elements had more evolutionary time to accumulate nucleotide changes that strengthened exon inclusion in the transcript products.


Diverse splicing patterns of exonized Alu elements in human tissues.

Lin L, Shen S, Tye A, Cai JJ, Jiang P, Davidson BL, Xing Y - PLoS Genet. (2008)

Most Alu exons with substantial transcript inclusion levels are derived from ancient Alu elements in the human genome.Plotted here are distributions of AluJ Class and AluS Class in the human genome, in Alu-derived internal exons, and in Alu-derived exons with substantial transcript inclusion levels based on our RT-PCR results. AluJ class is indicated by white column; AluS class is indicated by hatched column.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2562518&req=5

pgen-1000225-g004: Most Alu exons with substantial transcript inclusion levels are derived from ancient Alu elements in the human genome.Plotted here are distributions of AluJ Class and AluS Class in the human genome, in Alu-derived internal exons, and in Alu-derived exons with substantial transcript inclusion levels based on our RT-PCR results. AluJ class is indicated by white column; AluS class is indicated by hatched column.
Mentions: In this study, we conducted RT-PCR analysis of 38 Alu-derived exons in 10 human tissues. 26 of the 38 exons had at least medium inclusion levels in certain tissues. These exons are in genes from a wide range of functional categories (see the complete list in Table S2). Analyses of these 26 exons revealed several interesting characteristics. 23 of the 26 exons were derived from the antisense strand of Alu elements, among which 14 were from the right arm of the antisense Alu (see Figure S5), consistent with a recent report that the right arm of Alu antisense strand is a hotspot for exonization [53]. Moreover, of these 26 exons, 23 were from AluJ class and 3 were from the AluS class. By contrast, in the total set of Alu-derived exons in our study, 211 were from AluJ and 111 were from AluS, a 4-fold shift in the ratio of AluJ to AluS (7.7 in the “substantially included” set versus 1.9 in the total set; P = 0.01, one-tailed Fisher exact test). In the human genome, AluJ is outnumbered by AluS at a ratio of 1 to 2.3 [14] (Figure 4). The similar trend was also found in the 19 “correlated” exons; 16 were from the AluJ class and 3 were from the AluS class. Taken together, these data are consistent with the fact that AluJ is the oldest Alu subclass in the human genome [54], so that exons derived from AluJ elements had more evolutionary time to accumulate nucleotide changes that strengthened exon inclusion in the transcript products.

Bottom Line: Most of such exons are derived from ancient Alu elements in the genome.Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees.Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA.

ABSTRACT
Exonization of Alu elements is a major mechanism for birth of new exons in primate genomes. Prior analyses of expressed sequence tags show that almost all Alu-derived exons are alternatively spliced, and the vast majority of these exons have low transcript inclusion levels. In this work, we provide genomic and experimental evidence for diverse splicing patterns of exonized Alu elements in human tissues. Using Exon array data of 330 Alu-derived exons in 11 human tissues and detailed RT-PCR analyses of 38 exons, we show that some Alu-derived exons are constitutively spliced in a broad range of human tissues, and some display strong tissue-specific switch in their transcript inclusion levels. Most of such exons are derived from ancient Alu elements in the genome. In SEPN1, mutations of which are linked to a form of congenital muscular dystrophy, the muscle-specific inclusion of an Alu-derived exon may be important for regulating SEPN1 activity in muscle. Realtime qPCR analysis of this SEPN1 exon in macaque and chimpanzee tissues indicates human-specific increase in its transcript inclusion level and muscle specificity after the divergence of humans and chimpanzees. Our results imply that some Alu exonization events may have acquired adaptive benefits during the evolution of primate transcriptomes.

Show MeSH
Related in: MedlinePlus