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Contrasting 5' and 3' evolutionary histories and frequent evolutionary convergence in Meis/hth gene structures.

Irimia M, Maeso I, Burguera D, Hidalgo-Sánchez M, Puelles L, Roy SW, Garcia-Fernàndez J, Ferran JL - Genome Biol Evol (2011)

Bottom Line: Our study revealed three surprising results that suggest important and very different functions for Meis intron-exon structures.This contrasts with the high degree of structural divergence found in genome-wide studies and may attest to conserved regulatory elements residing within these conserved introns.These results attest to the importance of locus-specific splicing functions in differences in structural evolution across genes, as well as to commonalities of forces shaping the evolution of individual genes along different lineages.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, School of Biology, University of Barcelona, Barcelona, Spain. mirimia@gmail.com

ABSTRACT
Organisms show striking differences in genome structure; however, the functional implications and fundamental forces that govern these differences remain obscure. The intron-exon organization of nuclear genes is involved in a particularly large variety of structures and functional roles. We performed a 22-species study of Meis/hth genes, intron-rich homeodomain-containing transcription factors involved in a wide range of developmental processes. Our study revealed three surprising results that suggest important and very different functions for Meis intron-exon structures. First, we find unexpected conservation across species of intron positions and lengths along most of the Meis locus. This contrasts with the high degree of structural divergence found in genome-wide studies and may attest to conserved regulatory elements residing within these conserved introns. Second, we find very different evolutionary histories for the 5' and 3' regions of the gene. The 5'-most 10 exons, which encode the highly conserved Meis domain and homeodomain, show striking conservation. By contrast, the 3' of the gene, which encodes several domains implicated in transcriptional activation and response to cell signaling, shows a remarkably active evolutionary history, with diverse isoforms and frequent creation and loss of new exons and splice sites. This region-specific diversity suggests evolutionary "tinkering," with alternative splicing allowing for more subtle regulation of protein function. Third, we find a large number of cases of convergent evolution in the 3' region, including 1) parallel losses of ancestral coding sequence, 2) parallel gains of external and internal splice sites, and 3) recurrent truncation of C-terminal coding regions. These results attest to the importance of locus-specific splicing functions in differences in structural evolution across genes, as well as to commonalities of forces shaping the evolution of individual genes along different lineages.

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Evolution of the intron–exon structures of the C-termini of Meis/hth. (A) Schematic representation of the intron–exon structure of a prototypical vertebrate Meis gene. The conserved long size of introns 6–9 are indicated by a double slash. Homologous coding regions (exons) in the 3′ are indicated by colors: 10 (dark blue), 10′ (light blue), 11 (red), 12a (light green), and 12b (dark green). (B) Diversity of intron–exon structures of exons 10–12b in metazoans. The different genomic gains (+) and losses (−) of regions or splice sites (5′ splice site (SS) or 3′ ss, colored according to the exon), assuming parsimony, are indicated in the branches of the schematic tree on the left-hand side. Solid vertical bars between colors represent a conserved 5′ ss, and GC 5′ ss are indicated above each line. Asterisks represent termination codons and gray blocks indicate UTR exons. Split gray/colored boxes indicate regions that are either translated or 3′ UTR depending on splice form. (C) Sequence alignment for some representative bilaterians and the two non-bilaterians showing sequence conservation at each exon. Within the boxes, “1” indicates a phase 1 intron, and an asterisk represents absence of an intron at that position. Highlighted positions correspond to 60% of similar amino acid types across studied genes, as generated by BioEdit.
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fig1: Evolution of the intron–exon structures of the C-termini of Meis/hth. (A) Schematic representation of the intron–exon structure of a prototypical vertebrate Meis gene. The conserved long size of introns 6–9 are indicated by a double slash. Homologous coding regions (exons) in the 3′ are indicated by colors: 10 (dark blue), 10′ (light blue), 11 (red), 12a (light green), and 12b (dark green). (B) Diversity of intron–exon structures of exons 10–12b in metazoans. The different genomic gains (+) and losses (−) of regions or splice sites (5′ splice site (SS) or 3′ ss, colored according to the exon), assuming parsimony, are indicated in the branches of the schematic tree on the left-hand side. Solid vertical bars between colors represent a conserved 5′ ss, and GC 5′ ss are indicated above each line. Asterisks represent termination codons and gray blocks indicate UTR exons. Split gray/colored boxes indicate regions that are either translated or 3′ UTR depending on splice form. (C) Sequence alignment for some representative bilaterians and the two non-bilaterians showing sequence conservation at each exon. Within the boxes, “1” indicates a phase 1 intron, and an asterisk represents absence of an intron at that position. Highlighted positions correspond to 60% of similar amino acid types across studied genes, as generated by BioEdit.

Mentions: Most vertebrates contain three paralogs of Meis (Nakamura et al. 1996; Sánchez-Guardado et al. 2011), dating to the two rounds of whole-genome duplication (WGD) at the base of vertebrates (Dehal and Boore 2005; Putnam et al. 2008). Adding to MEIS protein diversity, Meis genes have been shown to be alternatively spliced. For instance, exon “12a” of the vertebrate Meis1 gene is alternatively spliced: the Meis1A isoform contains exon 12a (fig. 1A), but the Meis1B isoform does not, leading to an alternative C-terminus, encoded by the downstream exon 12b, and to higher transcriptional activator capacities than both Meis1A- and the Meis-related pknox1 gene, especially in response to protein kinase A (PKA) and TrichostatinA (TSA) (Maeda et al. 2001; Huang et al. 2005). Alternative splicing (AS) of exons homologous to 12a, as well as other AS events, have been reported for the Meis2 and Meis3 genes in vertebrates (Oulad-Abdelghani et al. 1997; Yang et al. 2000; Williams et al. 2005; Shim et al. 2007; Hyman-Walsh et al. 2010; Sánchez-Guardado et al. 2011).


Contrasting 5' and 3' evolutionary histories and frequent evolutionary convergence in Meis/hth gene structures.

Irimia M, Maeso I, Burguera D, Hidalgo-Sánchez M, Puelles L, Roy SW, Garcia-Fernàndez J, Ferran JL - Genome Biol Evol (2011)

Evolution of the intron–exon structures of the C-termini of Meis/hth. (A) Schematic representation of the intron–exon structure of a prototypical vertebrate Meis gene. The conserved long size of introns 6–9 are indicated by a double slash. Homologous coding regions (exons) in the 3′ are indicated by colors: 10 (dark blue), 10′ (light blue), 11 (red), 12a (light green), and 12b (dark green). (B) Diversity of intron–exon structures of exons 10–12b in metazoans. The different genomic gains (+) and losses (−) of regions or splice sites (5′ splice site (SS) or 3′ ss, colored according to the exon), assuming parsimony, are indicated in the branches of the schematic tree on the left-hand side. Solid vertical bars between colors represent a conserved 5′ ss, and GC 5′ ss are indicated above each line. Asterisks represent termination codons and gray blocks indicate UTR exons. Split gray/colored boxes indicate regions that are either translated or 3′ UTR depending on splice form. (C) Sequence alignment for some representative bilaterians and the two non-bilaterians showing sequence conservation at each exon. Within the boxes, “1” indicates a phase 1 intron, and an asterisk represents absence of an intron at that position. Highlighted positions correspond to 60% of similar amino acid types across studied genes, as generated by BioEdit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3140891&req=5

fig1: Evolution of the intron–exon structures of the C-termini of Meis/hth. (A) Schematic representation of the intron–exon structure of a prototypical vertebrate Meis gene. The conserved long size of introns 6–9 are indicated by a double slash. Homologous coding regions (exons) in the 3′ are indicated by colors: 10 (dark blue), 10′ (light blue), 11 (red), 12a (light green), and 12b (dark green). (B) Diversity of intron–exon structures of exons 10–12b in metazoans. The different genomic gains (+) and losses (−) of regions or splice sites (5′ splice site (SS) or 3′ ss, colored according to the exon), assuming parsimony, are indicated in the branches of the schematic tree on the left-hand side. Solid vertical bars between colors represent a conserved 5′ ss, and GC 5′ ss are indicated above each line. Asterisks represent termination codons and gray blocks indicate UTR exons. Split gray/colored boxes indicate regions that are either translated or 3′ UTR depending on splice form. (C) Sequence alignment for some representative bilaterians and the two non-bilaterians showing sequence conservation at each exon. Within the boxes, “1” indicates a phase 1 intron, and an asterisk represents absence of an intron at that position. Highlighted positions correspond to 60% of similar amino acid types across studied genes, as generated by BioEdit.
Mentions: Most vertebrates contain three paralogs of Meis (Nakamura et al. 1996; Sánchez-Guardado et al. 2011), dating to the two rounds of whole-genome duplication (WGD) at the base of vertebrates (Dehal and Boore 2005; Putnam et al. 2008). Adding to MEIS protein diversity, Meis genes have been shown to be alternatively spliced. For instance, exon “12a” of the vertebrate Meis1 gene is alternatively spliced: the Meis1A isoform contains exon 12a (fig. 1A), but the Meis1B isoform does not, leading to an alternative C-terminus, encoded by the downstream exon 12b, and to higher transcriptional activator capacities than both Meis1A- and the Meis-related pknox1 gene, especially in response to protein kinase A (PKA) and TrichostatinA (TSA) (Maeda et al. 2001; Huang et al. 2005). Alternative splicing (AS) of exons homologous to 12a, as well as other AS events, have been reported for the Meis2 and Meis3 genes in vertebrates (Oulad-Abdelghani et al. 1997; Yang et al. 2000; Williams et al. 2005; Shim et al. 2007; Hyman-Walsh et al. 2010; Sánchez-Guardado et al. 2011).

Bottom Line: Our study revealed three surprising results that suggest important and very different functions for Meis intron-exon structures.This contrasts with the high degree of structural divergence found in genome-wide studies and may attest to conserved regulatory elements residing within these conserved introns.These results attest to the importance of locus-specific splicing functions in differences in structural evolution across genes, as well as to commonalities of forces shaping the evolution of individual genes along different lineages.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetics, School of Biology, University of Barcelona, Barcelona, Spain. mirimia@gmail.com

ABSTRACT
Organisms show striking differences in genome structure; however, the functional implications and fundamental forces that govern these differences remain obscure. The intron-exon organization of nuclear genes is involved in a particularly large variety of structures and functional roles. We performed a 22-species study of Meis/hth genes, intron-rich homeodomain-containing transcription factors involved in a wide range of developmental processes. Our study revealed three surprising results that suggest important and very different functions for Meis intron-exon structures. First, we find unexpected conservation across species of intron positions and lengths along most of the Meis locus. This contrasts with the high degree of structural divergence found in genome-wide studies and may attest to conserved regulatory elements residing within these conserved introns. Second, we find very different evolutionary histories for the 5' and 3' regions of the gene. The 5'-most 10 exons, which encode the highly conserved Meis domain and homeodomain, show striking conservation. By contrast, the 3' of the gene, which encodes several domains implicated in transcriptional activation and response to cell signaling, shows a remarkably active evolutionary history, with diverse isoforms and frequent creation and loss of new exons and splice sites. This region-specific diversity suggests evolutionary "tinkering," with alternative splicing allowing for more subtle regulation of protein function. Third, we find a large number of cases of convergent evolution in the 3' region, including 1) parallel losses of ancestral coding sequence, 2) parallel gains of external and internal splice sites, and 3) recurrent truncation of C-terminal coding regions. These results attest to the importance of locus-specific splicing functions in differences in structural evolution across genes, as well as to commonalities of forces shaping the evolution of individual genes along different lineages.

Show MeSH
Related in: MedlinePlus