Antibodies, otherwise called Immunoglobulins (Ig), are among the best-known molecules. A notable issue is the origin and evolution of antibody. Here, an integrate view of the emergence of antibody in evolution, based on a literature survey across a wide range of prokaryotic and eukaryotic organisms, is provided. The Ig molecular architecture relies on the very ancient Ig domain. Its chemical features permit the formation of multiple domain chains, self- dimerization or association with different partners. The amino acid sequence of the Ig domain determines a compact structural core and allows a great conformational variability of flexible loops carrying out recognition functions. This key structural role accounts for its occurrence in numerous recognition molecules. The Ig domains that are found in different taxa, are distinguished in four types, IgV, IgC 1, IgC2 and IgI, based on different numbers and arrangements of the occurring ?-strands. Ig-like domains, defined as BIg domain, have been detected on prokaryotic cell surface, and a role in host cell adhesion has been hypothesized. Whether the similarity between BIg and eukaryotic Ig is related to genetic evolution or to the physico-chemical properties of amino acid motives driving the domain assembly is still under debate. IgV appears to be the oldest Ig domain since it has been found in an adhesion molecule of a living fossil sponge. IgV domain has been widely used by the recognition molecules of earlier vertebrates. However, only in the jawed vertebrates the V domains have gained an important structural role in forming the antigen-binding site. The sequence variation arose from the encounter between IgV domain encoding genes and the evolutionary lines leading to the enzymes involved in the mechanisms of somatic recombination and hypermutation. While IgC2 and IgI domains are present in both invertebrates and vertebrates, IgC1 domain is limited to jawed vertebrates and has been found only in the molecules of adaptive immunity. This observation supports the idea that key actors of the adaptive immune response, all using the novel IgC1domain type, emerged at the same time during the so-called immunological "Big Bang". Various antibody classes, each containing a different heavy chain isotype, differentiated during vertebrate evolution and acquired distinct functions in mucosal and systemic immunity. In mammals, in addition to heavy chain isotypes, subisotypes are distinguished on the basis of their functions. The evolution of immunoglobulins can thus be considered as a paradigmatic example of how diversity and specificity of molecular interactions between proteins can increase.
Reconstructing the evolutionary history of the antibody molecule
U Oreste;MR Coscia
2023
Abstract
Antibodies, otherwise called Immunoglobulins (Ig), are among the best-known molecules. A notable issue is the origin and evolution of antibody. Here, an integrate view of the emergence of antibody in evolution, based on a literature survey across a wide range of prokaryotic and eukaryotic organisms, is provided. The Ig molecular architecture relies on the very ancient Ig domain. Its chemical features permit the formation of multiple domain chains, self- dimerization or association with different partners. The amino acid sequence of the Ig domain determines a compact structural core and allows a great conformational variability of flexible loops carrying out recognition functions. This key structural role accounts for its occurrence in numerous recognition molecules. The Ig domains that are found in different taxa, are distinguished in four types, IgV, IgC 1, IgC2 and IgI, based on different numbers and arrangements of the occurring ?-strands. Ig-like domains, defined as BIg domain, have been detected on prokaryotic cell surface, and a role in host cell adhesion has been hypothesized. Whether the similarity between BIg and eukaryotic Ig is related to genetic evolution or to the physico-chemical properties of amino acid motives driving the domain assembly is still under debate. IgV appears to be the oldest Ig domain since it has been found in an adhesion molecule of a living fossil sponge. IgV domain has been widely used by the recognition molecules of earlier vertebrates. However, only in the jawed vertebrates the V domains have gained an important structural role in forming the antigen-binding site. The sequence variation arose from the encounter between IgV domain encoding genes and the evolutionary lines leading to the enzymes involved in the mechanisms of somatic recombination and hypermutation. While IgC2 and IgI domains are present in both invertebrates and vertebrates, IgC1 domain is limited to jawed vertebrates and has been found only in the molecules of adaptive immunity. This observation supports the idea that key actors of the adaptive immune response, all using the novel IgC1domain type, emerged at the same time during the so-called immunological "Big Bang". Various antibody classes, each containing a different heavy chain isotype, differentiated during vertebrate evolution and acquired distinct functions in mucosal and systemic immunity. In mammals, in addition to heavy chain isotypes, subisotypes are distinguished on the basis of their functions. The evolution of immunoglobulins can thus be considered as a paradigmatic example of how diversity and specificity of molecular interactions between proteins can increase.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
