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The evolution of extracellular fibrillins and their functional domains.

Piha-Gossack A, Sossin W, Reinhardt DP - PLoS ONE (2012)

Bottom Line: Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes.The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates.Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved.

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Hypothetical evolution of human fibrillins.An ancestral fibrillin (red) existed prior to the split of bilaterians from non-bilaterians. A gene duplication event (white triangle), presumably at the divergence of gnathostomes (jawed vertebrates) from agnathans (jawless fish), led to the genes for fibrillin-1 (orange) and the ancestral fibrillin-2 and -3 gene, coined as fibrillin-2/3 (purple), and further coincides with the appearance of elastin and the evolution of closed circulatory systems. A second duplication event (black triangle), coinciding with the evolution of tetrapods, led to the genes for fibrillin-2 (blue) and fibrillin-3 (green). The pre-eutherian fibrillin-3 gene underwent significant evolutionary changes to become present-day fibrillin-3. Taxonomic classifications and evolutionary divergence events are found in blue boxes and indicated by fork symbols, with dotted light gray connectors to the individual fibrillins. The upper classification shares a common ancestor with humans. Question marks indicate uncertainties as to whether the unique region appeared before or after the divergence of vertebrates from other chordates. Spacing between taxonomic classifications is not proportional to their evolutionary timeline. Identified conserved characteristic features and evolutionary events found in all analyzed fibrillins are highlighted in an orange-colored box with a black arrow. Evolutionary characteristics and events specific to individual fibrillins are shown in green boxes with solid connectors and circles. Important related evolutionary events are shown in a yellow box.
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pone-0033560-g007: Hypothetical evolution of human fibrillins.An ancestral fibrillin (red) existed prior to the split of bilaterians from non-bilaterians. A gene duplication event (white triangle), presumably at the divergence of gnathostomes (jawed vertebrates) from agnathans (jawless fish), led to the genes for fibrillin-1 (orange) and the ancestral fibrillin-2 and -3 gene, coined as fibrillin-2/3 (purple), and further coincides with the appearance of elastin and the evolution of closed circulatory systems. A second duplication event (black triangle), coinciding with the evolution of tetrapods, led to the genes for fibrillin-2 (blue) and fibrillin-3 (green). The pre-eutherian fibrillin-3 gene underwent significant evolutionary changes to become present-day fibrillin-3. Taxonomic classifications and evolutionary divergence events are found in blue boxes and indicated by fork symbols, with dotted light gray connectors to the individual fibrillins. The upper classification shares a common ancestor with humans. Question marks indicate uncertainties as to whether the unique region appeared before or after the divergence of vertebrates from other chordates. Spacing between taxonomic classifications is not proportional to their evolutionary timeline. Identified conserved characteristic features and evolutionary events found in all analyzed fibrillins are highlighted in an orange-colored box with a black arrow. Evolutionary characteristics and events specific to individual fibrillins are shown in green boxes with solid connectors and circles. Important related evolutionary events are shown in a yellow box.

Mentions: Using results from the conducted analysis, we studied the evolution of fibrillins throughout key points in evolution. The earliest form of an ancestral fibrillin sequence, still present in cnidarians, molluscs, annelids, arthropods, echinoderms, urochordates, cephalochordates and the vertebrate sea lamprey, already represents the majority of the characteristic domain pattern seen in human fibrillins. Notable differences include the lack of a unique region, replaced by a cbEGF-like domain followed by another cbEGF domain instead of EGF4, the absence of integrin-binding sites until the emergence of cephalochordates and agnathans, as well as the presence of an ancestral hybrid-like domain in place of the second hybrid domain in arthropods. At the time of the first gene duplication, which coincides with the divergence of jawed vertebrates and agnathans, the single fibrillin sequence had already acquired a unique region, the second mature hybrid domain and RGD sites in TB3 and TB4. The coincidence of the first gene duplication and the appearance of the unique regions with the evolutionary appearance of elastin highlight potentially important functions of the unique regions and the availability of more than one fibrillin for the development of elastic fibers and a closed circulatory system. Following the first duplication, one sequence underwent the loss of the TB3 RGD site, as well as several other changes, in order to form fibrillin-1, while the second sequence, coined as fibrillin-2/3, retained the characteristics of the parent sequence and sustained the introduction of a glycine-rich region. The second duplication event coincides with the evolution of tetrapods, thus allowing ray-finned fish to evolve in parallel and develop the present-day form of fibrillin-2/3 found in these species. Following this duplication, one fibrillin copy maintained the features of the parent sequence to become fibrillin-2, while the other, underwent significant evolutionary changes to form fibrillin-3. The transition of the initial tetrapod fibrillin-3 sequence to the fibrillin-3 sequence found in humans and other mammals includes the loss of the RGD site in TB3, the novel introduction of an RGD site in cbEGF18, as well as a reduction of the glycine‚ą∂proline ratio in the unique region. Divergence of the fibrillin-3 gene is observed with the evolution of mammals, evident through the loss of the RGD site in TB3 of monotremes and marsupials. Highly conserved sequences throughout the evolution of fibrillins include the pro-protein furin-type processing sites within the unique N- and C-terminal domains, indicating an evolutionarily conserved microfibril assembly mechanism with regards to pro-protein processing. Other notable highly conserved regions in all analyzed fibrillins are the cysteine patterns in the unique N- and C-terminal domains. The results from this study were used to propose key events for the evolution of the three human fibrillins (Fig. 7).


The evolution of extracellular fibrillins and their functional domains.

Piha-Gossack A, Sossin W, Reinhardt DP - PLoS ONE (2012)

Hypothetical evolution of human fibrillins.An ancestral fibrillin (red) existed prior to the split of bilaterians from non-bilaterians. A gene duplication event (white triangle), presumably at the divergence of gnathostomes (jawed vertebrates) from agnathans (jawless fish), led to the genes for fibrillin-1 (orange) and the ancestral fibrillin-2 and -3 gene, coined as fibrillin-2/3 (purple), and further coincides with the appearance of elastin and the evolution of closed circulatory systems. A second duplication event (black triangle), coinciding with the evolution of tetrapods, led to the genes for fibrillin-2 (blue) and fibrillin-3 (green). The pre-eutherian fibrillin-3 gene underwent significant evolutionary changes to become present-day fibrillin-3. Taxonomic classifications and evolutionary divergence events are found in blue boxes and indicated by fork symbols, with dotted light gray connectors to the individual fibrillins. The upper classification shares a common ancestor with humans. Question marks indicate uncertainties as to whether the unique region appeared before or after the divergence of vertebrates from other chordates. Spacing between taxonomic classifications is not proportional to their evolutionary timeline. Identified conserved characteristic features and evolutionary events found in all analyzed fibrillins are highlighted in an orange-colored box with a black arrow. Evolutionary characteristics and events specific to individual fibrillins are shown in green boxes with solid connectors and circles. Important related evolutionary events are shown in a yellow box.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3306419&req=5

pone-0033560-g007: Hypothetical evolution of human fibrillins.An ancestral fibrillin (red) existed prior to the split of bilaterians from non-bilaterians. A gene duplication event (white triangle), presumably at the divergence of gnathostomes (jawed vertebrates) from agnathans (jawless fish), led to the genes for fibrillin-1 (orange) and the ancestral fibrillin-2 and -3 gene, coined as fibrillin-2/3 (purple), and further coincides with the appearance of elastin and the evolution of closed circulatory systems. A second duplication event (black triangle), coinciding with the evolution of tetrapods, led to the genes for fibrillin-2 (blue) and fibrillin-3 (green). The pre-eutherian fibrillin-3 gene underwent significant evolutionary changes to become present-day fibrillin-3. Taxonomic classifications and evolutionary divergence events are found in blue boxes and indicated by fork symbols, with dotted light gray connectors to the individual fibrillins. The upper classification shares a common ancestor with humans. Question marks indicate uncertainties as to whether the unique region appeared before or after the divergence of vertebrates from other chordates. Spacing between taxonomic classifications is not proportional to their evolutionary timeline. Identified conserved characteristic features and evolutionary events found in all analyzed fibrillins are highlighted in an orange-colored box with a black arrow. Evolutionary characteristics and events specific to individual fibrillins are shown in green boxes with solid connectors and circles. Important related evolutionary events are shown in a yellow box.
Mentions: Using results from the conducted analysis, we studied the evolution of fibrillins throughout key points in evolution. The earliest form of an ancestral fibrillin sequence, still present in cnidarians, molluscs, annelids, arthropods, echinoderms, urochordates, cephalochordates and the vertebrate sea lamprey, already represents the majority of the characteristic domain pattern seen in human fibrillins. Notable differences include the lack of a unique region, replaced by a cbEGF-like domain followed by another cbEGF domain instead of EGF4, the absence of integrin-binding sites until the emergence of cephalochordates and agnathans, as well as the presence of an ancestral hybrid-like domain in place of the second hybrid domain in arthropods. At the time of the first gene duplication, which coincides with the divergence of jawed vertebrates and agnathans, the single fibrillin sequence had already acquired a unique region, the second mature hybrid domain and RGD sites in TB3 and TB4. The coincidence of the first gene duplication and the appearance of the unique regions with the evolutionary appearance of elastin highlight potentially important functions of the unique regions and the availability of more than one fibrillin for the development of elastic fibers and a closed circulatory system. Following the first duplication, one sequence underwent the loss of the TB3 RGD site, as well as several other changes, in order to form fibrillin-1, while the second sequence, coined as fibrillin-2/3, retained the characteristics of the parent sequence and sustained the introduction of a glycine-rich region. The second duplication event coincides with the evolution of tetrapods, thus allowing ray-finned fish to evolve in parallel and develop the present-day form of fibrillin-2/3 found in these species. Following this duplication, one fibrillin copy maintained the features of the parent sequence to become fibrillin-2, while the other, underwent significant evolutionary changes to form fibrillin-3. The transition of the initial tetrapod fibrillin-3 sequence to the fibrillin-3 sequence found in humans and other mammals includes the loss of the RGD site in TB3, the novel introduction of an RGD site in cbEGF18, as well as a reduction of the glycine‚ą∂proline ratio in the unique region. Divergence of the fibrillin-3 gene is observed with the evolution of mammals, evident through the loss of the RGD site in TB3 of monotremes and marsupials. Highly conserved sequences throughout the evolution of fibrillins include the pro-protein furin-type processing sites within the unique N- and C-terminal domains, indicating an evolutionarily conserved microfibril assembly mechanism with regards to pro-protein processing. Other notable highly conserved regions in all analyzed fibrillins are the cysteine patterns in the unique N- and C-terminal domains. The results from this study were used to propose key events for the evolution of the three human fibrillins (Fig. 7).

Bottom Line: Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes.The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates.Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.

ABSTRACT
Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates and vertebrates, while the integrin-binding site within cbEGF18 of fibrillin-3 is a recent evolutionary change. The proline-rich domain in fibrillin-1, glycine-rich domain in fibrillin-2 and proline-/glycine-rich domain in fibrillin-3 are found in all analyzed tetrapod species, whereas it is completely replaced with an EGF-like domain in cnidarians, arthropods, molluscs and urochordates. All collected sequences contain the first 9-cysteine hybrid domain, and the second 8-cysteine hybrid domain with exception of arthropods containing an atypical 10-cysteine hybrid domain 2. Furin cleavage sites within the N- and C-terminal unique domains were found for all analyzed fibrillin sequences, indicating an essential role for processing of the fibrillin pro-proteins. The four cysteines in the unique N-terminus and the two cysteines in the unique C-terminus are also highly conserved.

Show MeSH