- #36
gravenewworld
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From an evolutionary molecular biology perspective, this may be controversial in some circles and it isn't my field of expertise, but one idea that has been floated out there is related to the absolutely unique ways that humans postranslationally modify proteins. For example, sialic acids became prominent late in evolution, primarily in animals of deuterostome lineage which comprises the vertebrates and some “higher” invertebrates that emerged at the Cambrian expansion. With rare exceptions, sialic acids are not generally found in plants or in most prokaryotes or invertebrates. There have been a few reports of sialic acids in mollusks, such as octopus and squid, and insects such as Drosophila. Genes structurally related to those involved in vertebrate sialic metabolism have been reported in insects and plants, and even in Archaea. Sialic are now often found in membrane macromolecules of microorganisms with newer lab techniques. Overall, it appears that sialic acids may be a more ancient Precambrian invention, but they were then either eliminated or used only sparingly in many lineages—finally flowering into prominence only in deuterostome lineage. Genetic evidence also suggests that the original invention of sialic acids may have derived from homologous gene products that synthesize keto-deoxyoctulosonic acid (Kdo). Certain strains of bacteria can contain large amounts of sialic acids or other 2-keto-3-deoxynononic acids in their capsular polysaccharides and/or lipooligosaccharides. Some of these bacteria are pathogenic and cell-surface sialic acids protect them from complement activation and/or antibody production. Thus, although definitive proof has not been obtained, the possibility of gene transfer from host eukaryotes exists. Interestingly, there is wide variation in sialic acid expression and complexity within deuterostome lineage, with the sialome of echinoderms appearing very complex and that of humans being more simple. However, expression of hydroxylated forms of sialic acids and O-acetylated sialic acids is highly conserved in deuterostomes, although exceptions exist, such as the lack of hydroxylated sialic acids in man, chicken, and some other birds.
So what does this have to do with evolution and why haven't other species involved intelligence like us? The most prominent example in this case is related to polysialylic acid (PSA) addition on neural cell adhesion molecule 1 (NCAM1). NCAM1 is a cell surface adhesion protein on neurons that is vitally important for memory, learning, and plasticity. NCAM1, along with another protein called L1, interact homophilically to fasiculate neurons together. However, when PSA is added to NCAM1, NCAM1 and L1 can no longer interact--in otherwords, PSA addition to NCAM1 is another layer of control over the way neurons can remodel themselves. The importance of PSA on NCAM1s can not be overstated. In addition to regulating the way neurons in the adult brain can remodel, NCAM1s and PSA regulate the way neurons move throughout the body espeically in neural crest-derived tissues during development. Additionally, genetic variation of ST8SIA2, the gene responsible for polysialylation of NCAM1, is associated with increased susceptibility to bipolar disorder, schizophrenia, and autism. More and more evidence piles on all of the time for the role of polysialylation in the brain development.
To visualize PSA, see here (top polymer):
http://glycoforum.gr.jp/science/word/gif9909/gt-c01-fig1.gif
During metabolism of glucose into sialic acids in organisms other than huamans a gene named CMAH encodes for the enzyme that hydroxylates sialic acid into Neu5Gc the structure of which is here:
http://www.glycoforum.gr.jp/science/glycogenes/06/1.gif
As was stated above, one of the things that makes us uniquely human is the fact that we do no have Neu5Gc on our cells. The explanation for this is due to an inactivating exon deletion in the CMAH gene that occurred after our last common ancestor with the African great apes. If you can see what I'm getting at, the monomers that make up PSA in humans are not hydroxylated, and PSA in humans is not made out of a polymer of Neu5Gcs. The importance of this slight chemical alteration is quite profound--many experiments have been performed that have shown that when Neu5Gc is engineered onto the surface of human cells, you can induce immune responses. And as was previously discussed, PSA modulation of NCAM1s has a profound influence on brain development, learning, and memory. Why haven't animals evolved human like intelligence? One reason could be due to either lack of proper sialic acid metabolism and/or deletion or mutational impairment of their CMAH gene which is responsible for their production of Neu5Gc that may be preventing their brains from rewiring themselves to develop human like intelligence.
So what does this have to do with evolution and why haven't other species involved intelligence like us? The most prominent example in this case is related to polysialylic acid (PSA) addition on neural cell adhesion molecule 1 (NCAM1). NCAM1 is a cell surface adhesion protein on neurons that is vitally important for memory, learning, and plasticity. NCAM1, along with another protein called L1, interact homophilically to fasiculate neurons together. However, when PSA is added to NCAM1, NCAM1 and L1 can no longer interact--in otherwords, PSA addition to NCAM1 is another layer of control over the way neurons can remodel themselves. The importance of PSA on NCAM1s can not be overstated. In addition to regulating the way neurons in the adult brain can remodel, NCAM1s and PSA regulate the way neurons move throughout the body espeically in neural crest-derived tissues during development. Additionally, genetic variation of ST8SIA2, the gene responsible for polysialylation of NCAM1, is associated with increased susceptibility to bipolar disorder, schizophrenia, and autism. More and more evidence piles on all of the time for the role of polysialylation in the brain development.
To visualize PSA, see here (top polymer):
http://glycoforum.gr.jp/science/word/gif9909/gt-c01-fig1.gif
During metabolism of glucose into sialic acids in organisms other than huamans a gene named CMAH encodes for the enzyme that hydroxylates sialic acid into Neu5Gc the structure of which is here:
http://www.glycoforum.gr.jp/science/glycogenes/06/1.gif
As was stated above, one of the things that makes us uniquely human is the fact that we do no have Neu5Gc on our cells. The explanation for this is due to an inactivating exon deletion in the CMAH gene that occurred after our last common ancestor with the African great apes. If you can see what I'm getting at, the monomers that make up PSA in humans are not hydroxylated, and PSA in humans is not made out of a polymer of Neu5Gcs. The importance of this slight chemical alteration is quite profound--many experiments have been performed that have shown that when Neu5Gc is engineered onto the surface of human cells, you can induce immune responses. And as was previously discussed, PSA modulation of NCAM1s has a profound influence on brain development, learning, and memory. Why haven't animals evolved human like intelligence? One reason could be due to either lack of proper sialic acid metabolism and/or deletion or mutational impairment of their CMAH gene which is responsible for their production of Neu5Gc that may be preventing their brains from rewiring themselves to develop human like intelligence.
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