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Fc receptors for immunoglobulins and their appearance during vertebrate evolution.

Akula S, Mohammadamin S, Hellman L - PLoS ONE (2014)

Bottom Line: These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish.In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance.Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.

ABSTRACT
Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

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The immunoglobulin heavy chain locus of a panel of selected vertebrates from fish to humans.The locus depicts every single gene as a block and without individual exons. The figure is not to scale and the genes have been color coded; IgM in black, IgD in dark green, IgA and IgX in light green, IgY in magenta, IgG in blue, IgE in purple, IgO in red, IgZ in yellow, IgF in orange and pseudogenes in shaded grey or purple.
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pone-0096903-g001: The immunoglobulin heavy chain locus of a panel of selected vertebrates from fish to humans.The locus depicts every single gene as a block and without individual exons. The figure is not to scale and the genes have been color coded; IgM in black, IgD in dark green, IgA and IgX in light green, IgY in magenta, IgG in blue, IgE in purple, IgO in red, IgZ in yellow, IgF in orange and pseudogenes in shaded grey or purple.

Mentions: Immunoglobulins (Igs) are only found in jawed vertebrates and there are strong indications that the complexity of the adaptive immune system has increased gradually during vertebrate evolution. The effector functions of the Igs have separated into different Ig classes thereby increasing the regulatory potential of the immune system. Mammals express up to six different Ig classes: IgM, IgD, IgG, IgE, IgA and IgO, and the total number of isotypes can sometimes exceed 15 (Figure 1) [1]. Of these six Ig classes only IgM and IgD have been found in fish, which tend to have only two to three Ig classes and isotypes. In fish, the list of Ig classes now also includes IgW, IgNAR, IgT and IgZ [2]–[6]. In general, amphibians have four to five classes of Igs: IgM, IgD, IgA/IgX, IgY and one additional class named IgF or IgP [7], [8]. Neither IgA nor IgY is found in fish and IgG and IgE have not been identified in reptiles, amphibians or birds, suggesting they are unique for mammals [9]. Birds have only three Ig classes: IgM, IgA and IgY (Figure 1). However, this low number is most likely a result of a loss of isotypes as massive losses and re-expansion of genes and gene families have occurred in birds [10]. Interestingly, other members of the reptile lineage have instead experienced massive expansions like the Chinese alligator, which has 10 isotypes, although neither IgG nor IgE [4]. All major classes in placental mammals are also present in monotremes, the egg-laying mammals. The platypus has been shown to express six classes and eight different isotypes: IgM, IgG1, IgG2, IgA1, IgA2, IgE, IgD and IgO (Figure 1) [1], [11]–[14]. Marsupials, as represented by the American opossum have IgM, IgG, IgA and IgE, but no IgD gene [15], [16]. The gene for IgD has probably been lost in this lineage (Figure 1) [17]. These findings indicate that the number of Ig classes and isotypes has increased during vertebrate evolution from two to three in fish, to sometimes more than fifteen in mammals (Figure 1). The most important steps in this increase have probably been the duplication of IgM forming the early ancestor of IgY. This seems to have occurred at the emergence of the tetrapods, The second step was most likely a duplication of IgM, forming the ancestor of IgA/X. This isotype is also first observed in amphibians. The third major step was the duplication of IgY forming IgG and IgE. However, losses of classes and isotypes have also occurred as exemplified by the loss of IgD in birds and marsupials. Interestingly, the chicken has only one light chain isotype, whereas mammals have two and many fish species have three, indicating that birds have lost two light chain loci. The increase in the number of different Ig classes and isotypes observed in many tetrapods has likely been accompanied by a similar increase in isotype-specific receptors. However, how this increase has occurred is still only partly understood.


Fc receptors for immunoglobulins and their appearance during vertebrate evolution.

Akula S, Mohammadamin S, Hellman L - PLoS ONE (2014)

The immunoglobulin heavy chain locus of a panel of selected vertebrates from fish to humans.The locus depicts every single gene as a block and without individual exons. The figure is not to scale and the genes have been color coded; IgM in black, IgD in dark green, IgA and IgX in light green, IgY in magenta, IgG in blue, IgE in purple, IgO in red, IgZ in yellow, IgF in orange and pseudogenes in shaded grey or purple.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016189&req=5

pone-0096903-g001: The immunoglobulin heavy chain locus of a panel of selected vertebrates from fish to humans.The locus depicts every single gene as a block and without individual exons. The figure is not to scale and the genes have been color coded; IgM in black, IgD in dark green, IgA and IgX in light green, IgY in magenta, IgG in blue, IgE in purple, IgO in red, IgZ in yellow, IgF in orange and pseudogenes in shaded grey or purple.
Mentions: Immunoglobulins (Igs) are only found in jawed vertebrates and there are strong indications that the complexity of the adaptive immune system has increased gradually during vertebrate evolution. The effector functions of the Igs have separated into different Ig classes thereby increasing the regulatory potential of the immune system. Mammals express up to six different Ig classes: IgM, IgD, IgG, IgE, IgA and IgO, and the total number of isotypes can sometimes exceed 15 (Figure 1) [1]. Of these six Ig classes only IgM and IgD have been found in fish, which tend to have only two to three Ig classes and isotypes. In fish, the list of Ig classes now also includes IgW, IgNAR, IgT and IgZ [2]–[6]. In general, amphibians have four to five classes of Igs: IgM, IgD, IgA/IgX, IgY and one additional class named IgF or IgP [7], [8]. Neither IgA nor IgY is found in fish and IgG and IgE have not been identified in reptiles, amphibians or birds, suggesting they are unique for mammals [9]. Birds have only three Ig classes: IgM, IgA and IgY (Figure 1). However, this low number is most likely a result of a loss of isotypes as massive losses and re-expansion of genes and gene families have occurred in birds [10]. Interestingly, other members of the reptile lineage have instead experienced massive expansions like the Chinese alligator, which has 10 isotypes, although neither IgG nor IgE [4]. All major classes in placental mammals are also present in monotremes, the egg-laying mammals. The platypus has been shown to express six classes and eight different isotypes: IgM, IgG1, IgG2, IgA1, IgA2, IgE, IgD and IgO (Figure 1) [1], [11]–[14]. Marsupials, as represented by the American opossum have IgM, IgG, IgA and IgE, but no IgD gene [15], [16]. The gene for IgD has probably been lost in this lineage (Figure 1) [17]. These findings indicate that the number of Ig classes and isotypes has increased during vertebrate evolution from two to three in fish, to sometimes more than fifteen in mammals (Figure 1). The most important steps in this increase have probably been the duplication of IgM forming the early ancestor of IgY. This seems to have occurred at the emergence of the tetrapods, The second step was most likely a duplication of IgM, forming the ancestor of IgA/X. This isotype is also first observed in amphibians. The third major step was the duplication of IgY forming IgG and IgE. However, losses of classes and isotypes have also occurred as exemplified by the loss of IgD in birds and marsupials. Interestingly, the chicken has only one light chain isotype, whereas mammals have two and many fish species have three, indicating that birds have lost two light chain loci. The increase in the number of different Ig classes and isotypes observed in many tetrapods has likely been accompanied by a similar increase in isotype-specific receptors. However, how this increase has occurred is still only partly understood.

Bottom Line: These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish.In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance.Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell and Molecular Biology, Uppsala University, The Biomedical Center, Uppsala, Sweden.

ABSTRACT
Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR γ chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

Show MeSH