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Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes.

Cañestro C, Catchen JM, Rodríguez-Marí A, Yokoi H, Postlethwait JH - PLoS Genet. (2009)

Bottom Line: Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival.We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications.Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA.

ABSTRACT
Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

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Phylogenetic tree of the vertebrate Aldh1A gene family.All phylogenetic methodologies (Bayesian, Maximum-likelihood, Neighbor-joining and Maximum-parsimony; included in Figure S1) agreed on a unique gene topology in which Aldh1a1 (green background) and Aldh1a2 (tan background) are the closest sister clades, while Aldh1a3 (blue background) diverged basally: ((Aldh1a1, Aldh1a2), Aldh1a3). Values at nodes correspond to the posterior probabilities inferred from the Bayesian method and generally show a highly supported tree topology. The only exception is a moderately high value of 0.76 for the Aldh1a1-Aldh1a2 node (for this node, the ML, NJ and MP supporting values are also shown). While Aldh1a2 and Aldh1a3 are present in both tetrapods (red lines) and teleosts (blue lines), Aldh1a1 is absent from teleost genomes. Scale bar indicates amino-acid substitutions. Tetrapods: Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus novergicus; Gg, Gallus gallus; Xt, Xenopus tropicalis; Teleosts: Dr, Danio rerio; Ga, Gasterosteus aculeatus; Ol, Oryzias latipes; Tn, Tetraodon nigroviridis; Tr, Takifugu rubripes; Cephalochordates: Bf, Branchiostoma floridae.
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pgen-1000496-g001: Phylogenetic tree of the vertebrate Aldh1A gene family.All phylogenetic methodologies (Bayesian, Maximum-likelihood, Neighbor-joining and Maximum-parsimony; included in Figure S1) agreed on a unique gene topology in which Aldh1a1 (green background) and Aldh1a2 (tan background) are the closest sister clades, while Aldh1a3 (blue background) diverged basally: ((Aldh1a1, Aldh1a2), Aldh1a3). Values at nodes correspond to the posterior probabilities inferred from the Bayesian method and generally show a highly supported tree topology. The only exception is a moderately high value of 0.76 for the Aldh1a1-Aldh1a2 node (for this node, the ML, NJ and MP supporting values are also shown). While Aldh1a2 and Aldh1a3 are present in both tetrapods (red lines) and teleosts (blue lines), Aldh1a1 is absent from teleost genomes. Scale bar indicates amino-acid substitutions. Tetrapods: Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus novergicus; Gg, Gallus gallus; Xt, Xenopus tropicalis; Teleosts: Dr, Danio rerio; Ga, Gasterosteus aculeatus; Ol, Oryzias latipes; Tn, Tetraodon nigroviridis; Tr, Takifugu rubripes; Cephalochordates: Bf, Branchiostoma floridae.

Mentions: To understand the history of gene gain and loss in the Aldh1a family, it is important to first understand the phylogeny of family members. Unfortunately, evolutionary relationships among vertebrate Aldh1a paralogs are currently unclear. In one analysis, the three vertebrate Aldh1a clades collapsed to an unresolved trichotomy [59], and in another, Aldh1a2 and Aldh1a3 appeared as sister groups (Aldh1a1, (Aldh1a2, Aldh1a3)), supported by low bootstrap values [65]. These problems may stem from sequence similarities among the Aldh1a1, Aldh1a2 and Aldh1a3 proteins and the use of the evolutionarily distant mitochondrial Aldh2 family to root the tree. To overcome this uncertainty, we turned to a chordate outgroup, the cephalochordate amphioxus, whose lineage diverged from that of the vertebrates before the R1 and R2 events [66],[67]. Amphioxus has both Aldh1a and Aldh2 gene families [59], and hence its Aldh1a genes are much more closely related to vertebrate Aldh1a1 genes than is the Aldh2 gene family. We found that several different phylogenetic methodologies, including Bayesian inference, Maximum-likelihood, gamma-corrected Neighbor-Joining and Maximum-Parsimony all agreed on the same tree topology ((Aldh1a1, Aldh1a2), Aldh1a3)), with Aldh1a1 and Aldh1a2 as sister groups (Figures 1 and S1). This phylogeny differs from both published results: the trichotomy result and the view of Aldh1a2 and Aldh1a3 as sister clades [59],[65]. Our results still provided only a moderately high probability of 0.76 supporting the Aldh1a1/2 clade under the Bayesian phylogenetic inference (Figure 1); thus, phylogenetic analysis alone is insufficient to definitively resolve Aldh1a relationships. To further test historical relationships among Aldh1a paralogs, we examined a data set independent of Aldh1a gene sequence by conducting comparative genomic analyses of the entire genomic neighborhoods (GN) surrounding Aldh1a genes in the genomes of humans and other vertebrates.


Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes.

Cañestro C, Catchen JM, Rodríguez-Marí A, Yokoi H, Postlethwait JH - PLoS Genet. (2009)

Phylogenetic tree of the vertebrate Aldh1A gene family.All phylogenetic methodologies (Bayesian, Maximum-likelihood, Neighbor-joining and Maximum-parsimony; included in Figure S1) agreed on a unique gene topology in which Aldh1a1 (green background) and Aldh1a2 (tan background) are the closest sister clades, while Aldh1a3 (blue background) diverged basally: ((Aldh1a1, Aldh1a2), Aldh1a3). Values at nodes correspond to the posterior probabilities inferred from the Bayesian method and generally show a highly supported tree topology. The only exception is a moderately high value of 0.76 for the Aldh1a1-Aldh1a2 node (for this node, the ML, NJ and MP supporting values are also shown). While Aldh1a2 and Aldh1a3 are present in both tetrapods (red lines) and teleosts (blue lines), Aldh1a1 is absent from teleost genomes. Scale bar indicates amino-acid substitutions. Tetrapods: Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus novergicus; Gg, Gallus gallus; Xt, Xenopus tropicalis; Teleosts: Dr, Danio rerio; Ga, Gasterosteus aculeatus; Ol, Oryzias latipes; Tn, Tetraodon nigroviridis; Tr, Takifugu rubripes; Cephalochordates: Bf, Branchiostoma floridae.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2682703&req=5

pgen-1000496-g001: Phylogenetic tree of the vertebrate Aldh1A gene family.All phylogenetic methodologies (Bayesian, Maximum-likelihood, Neighbor-joining and Maximum-parsimony; included in Figure S1) agreed on a unique gene topology in which Aldh1a1 (green background) and Aldh1a2 (tan background) are the closest sister clades, while Aldh1a3 (blue background) diverged basally: ((Aldh1a1, Aldh1a2), Aldh1a3). Values at nodes correspond to the posterior probabilities inferred from the Bayesian method and generally show a highly supported tree topology. The only exception is a moderately high value of 0.76 for the Aldh1a1-Aldh1a2 node (for this node, the ML, NJ and MP supporting values are also shown). While Aldh1a2 and Aldh1a3 are present in both tetrapods (red lines) and teleosts (blue lines), Aldh1a1 is absent from teleost genomes. Scale bar indicates amino-acid substitutions. Tetrapods: Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus novergicus; Gg, Gallus gallus; Xt, Xenopus tropicalis; Teleosts: Dr, Danio rerio; Ga, Gasterosteus aculeatus; Ol, Oryzias latipes; Tn, Tetraodon nigroviridis; Tr, Takifugu rubripes; Cephalochordates: Bf, Branchiostoma floridae.
Mentions: To understand the history of gene gain and loss in the Aldh1a family, it is important to first understand the phylogeny of family members. Unfortunately, evolutionary relationships among vertebrate Aldh1a paralogs are currently unclear. In one analysis, the three vertebrate Aldh1a clades collapsed to an unresolved trichotomy [59], and in another, Aldh1a2 and Aldh1a3 appeared as sister groups (Aldh1a1, (Aldh1a2, Aldh1a3)), supported by low bootstrap values [65]. These problems may stem from sequence similarities among the Aldh1a1, Aldh1a2 and Aldh1a3 proteins and the use of the evolutionarily distant mitochondrial Aldh2 family to root the tree. To overcome this uncertainty, we turned to a chordate outgroup, the cephalochordate amphioxus, whose lineage diverged from that of the vertebrates before the R1 and R2 events [66],[67]. Amphioxus has both Aldh1a and Aldh2 gene families [59], and hence its Aldh1a genes are much more closely related to vertebrate Aldh1a1 genes than is the Aldh2 gene family. We found that several different phylogenetic methodologies, including Bayesian inference, Maximum-likelihood, gamma-corrected Neighbor-Joining and Maximum-Parsimony all agreed on the same tree topology ((Aldh1a1, Aldh1a2), Aldh1a3)), with Aldh1a1 and Aldh1a2 as sister groups (Figures 1 and S1). This phylogeny differs from both published results: the trichotomy result and the view of Aldh1a2 and Aldh1a3 as sister clades [59],[65]. Our results still provided only a moderately high probability of 0.76 supporting the Aldh1a1/2 clade under the Bayesian phylogenetic inference (Figure 1); thus, phylogenetic analysis alone is insufficient to definitively resolve Aldh1a relationships. To further test historical relationships among Aldh1a paralogs, we examined a data set independent of Aldh1a gene sequence by conducting comparative genomic analyses of the entire genomic neighborhoods (GN) surrounding Aldh1a genes in the genomes of humans and other vertebrates.

Bottom Line: Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival.We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications.Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

View Article: PubMed Central - PubMed

Affiliation: Institute of Neuroscience, University of Oregon, Eugene, OR, USA.

ABSTRACT
Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Show MeSH