Limits...
FoxO gene family evolution in vertebrates.

Wang M, Zhang X, Zhao H, Wang Q, Pan Y - BMC Evol. Biol. (2009)

Bottom Line: Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection.The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, 200240, PR China. wangmh-1981@sjtu.edu.cn

ABSTRACT

Background: Forkhead box, class O (FoxO) belongs to the large family of forkhead transcription factors that are characterized by a conserved forkhead box DNA-binding domain. To date, the FoxO group has four mammalian members: FoxO1, FoxO3a, FoxO4 and FoxO6, which are orthologs of DAF16, an insulin-responsive transcription factor involved in regulating longevity of worms and flies. The degree of homology between these four members is high, especially in the forkhead domain, which contains the DNA-binding interface. Yet, mouse FoxO knockouts have revealed that each FoxO gene has its unique role in the physiological process. Whether the functional divergences are primarily due to adaptive selection pressure or relaxed selective constraint remains an open question. As such, this study aims to address the evolutionary mode of FoxO, which may lead to the functional divergence.

Results: Sequence similarity searches have performed in genome and scaffold data to identify homologues of FoxO in vertebrates. Phylogenetic analysis was used to characterize the family evolutionary history by identifying two duplications early in vertebrate evolution. To determine the mode of evolution in vertebrates, we performed a rigorous statistical analysis with FoxO gene sequences, including relative rate ratio tests, branch-specific dN/dS ratio tests, site-specific dN/dS ratio tests, branch-site dN/dS ratio tests and clade level amino acid conservation/variation patterns analysis. Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection. The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.

Conclusion: We present a phylogeny describing the evolutionary history of the FoxO gene family and show that the genes have evolved through duplications followed by purifying selection except for four sites in FoxO6 fixed by positive selection lie mostly within the non-conserved optimal PKB motif in the C-terminal part. Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.

Show MeSH
Phylogenetic relationships of DNA sequences within the FoxO family. Phylogenetic tree based on the nucleotide sequence data. The numbers indicate the Bayesian probabilities for each phylogenetic clade. Shaded boxes denote the four lineages and one outgroup. The scale bars represent codon substitutions per site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2746812&req=5

Figure 1: Phylogenetic relationships of DNA sequences within the FoxO family. Phylogenetic tree based on the nucleotide sequence data. The numbers indicate the Bayesian probabilities for each phylogenetic clade. Shaded boxes denote the four lineages and one outgroup. The scale bars represent codon substitutions per site.

Mentions: To study the molecular evolution of vertebrate FoxO genes, we carried out phylogenetic inference analyses based on codon alignment and inferred their evolutionary history using Bayesian methods. We used the Bayesian posterior probabilities (PPs) of each node to evaluate clades support. Figure 1 shows the consensus phylogeny obtained for FoxO gene sequences. The vertebrate FoxOs were assorted well to four lineages according to their FoxO classification, all with high PP support values (a poorly supported position: 0.99 PP) indicating that the formation of the paralogous lineages occurred before the divergence of individual species, and the orthologs FoxOs (Cifoxo, BfFoxOA and SpFoxOl) from amphioxus (Branchiostoma floridae), Ciona intestinalis and Strongylocentrotus purpuratus were just located as an outgroup of their assigned lineages. From Figure 1, we inferred that two major duplications had occurred early in the vertebrate lineages. The first duplication led to the emergence of two lineages which evolved into FoxO3/6 and FoxO1/4, and the second duplication, also early in vertebrate evolution, resulted in FoxO6 and FoxO3, and FoxO1 and FoxO4. Phylogenetic tree shows that the FoxO6 gene cluster has long branches, an indication of fast-evolving lineage with a large number of structural changes accumulating on them.


FoxO gene family evolution in vertebrates.

Wang M, Zhang X, Zhao H, Wang Q, Pan Y - BMC Evol. Biol. (2009)

Phylogenetic relationships of DNA sequences within the FoxO family. Phylogenetic tree based on the nucleotide sequence data. The numbers indicate the Bayesian probabilities for each phylogenetic clade. Shaded boxes denote the four lineages and one outgroup. The scale bars represent codon substitutions per site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2746812&req=5

Figure 1: Phylogenetic relationships of DNA sequences within the FoxO family. Phylogenetic tree based on the nucleotide sequence data. The numbers indicate the Bayesian probabilities for each phylogenetic clade. Shaded boxes denote the four lineages and one outgroup. The scale bars represent codon substitutions per site.
Mentions: To study the molecular evolution of vertebrate FoxO genes, we carried out phylogenetic inference analyses based on codon alignment and inferred their evolutionary history using Bayesian methods. We used the Bayesian posterior probabilities (PPs) of each node to evaluate clades support. Figure 1 shows the consensus phylogeny obtained for FoxO gene sequences. The vertebrate FoxOs were assorted well to four lineages according to their FoxO classification, all with high PP support values (a poorly supported position: 0.99 PP) indicating that the formation of the paralogous lineages occurred before the divergence of individual species, and the orthologs FoxOs (Cifoxo, BfFoxOA and SpFoxOl) from amphioxus (Branchiostoma floridae), Ciona intestinalis and Strongylocentrotus purpuratus were just located as an outgroup of their assigned lineages. From Figure 1, we inferred that two major duplications had occurred early in the vertebrate lineages. The first duplication led to the emergence of two lineages which evolved into FoxO3/6 and FoxO1/4, and the second duplication, also early in vertebrate evolution, resulted in FoxO6 and FoxO3, and FoxO1 and FoxO4. Phylogenetic tree shows that the FoxO6 gene cluster has long branches, an indication of fast-evolving lineage with a large number of structural changes accumulating on them.

Bottom Line: Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection.The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Agriculture and Biology, Department of Animal Sciences, Shanghai Jiao Tong University, Shanghai, 200240, PR China. wangmh-1981@sjtu.edu.cn

ABSTRACT

Background: Forkhead box, class O (FoxO) belongs to the large family of forkhead transcription factors that are characterized by a conserved forkhead box DNA-binding domain. To date, the FoxO group has four mammalian members: FoxO1, FoxO3a, FoxO4 and FoxO6, which are orthologs of DAF16, an insulin-responsive transcription factor involved in regulating longevity of worms and flies. The degree of homology between these four members is high, especially in the forkhead domain, which contains the DNA-binding interface. Yet, mouse FoxO knockouts have revealed that each FoxO gene has its unique role in the physiological process. Whether the functional divergences are primarily due to adaptive selection pressure or relaxed selective constraint remains an open question. As such, this study aims to address the evolutionary mode of FoxO, which may lead to the functional divergence.

Results: Sequence similarity searches have performed in genome and scaffold data to identify homologues of FoxO in vertebrates. Phylogenetic analysis was used to characterize the family evolutionary history by identifying two duplications early in vertebrate evolution. To determine the mode of evolution in vertebrates, we performed a rigorous statistical analysis with FoxO gene sequences, including relative rate ratio tests, branch-specific dN/dS ratio tests, site-specific dN/dS ratio tests, branch-site dN/dS ratio tests and clade level amino acid conservation/variation patterns analysis. Our results suggest that FoxO is constrained by strong purifying selection except four sites in FoxO6, which have undergone positive Darwinian selection. The functional divergence in this family is best explained by either relaxed purifying selection or positive selection.

Conclusion: We present a phylogeny describing the evolutionary history of the FoxO gene family and show that the genes have evolved through duplications followed by purifying selection except for four sites in FoxO6 fixed by positive selection lie mostly within the non-conserved optimal PKB motif in the C-terminal part. Relaxed selection may play important roles in the process of functional differentiation evolved through gene duplications as well.

Show MeSH