The Joining chain (J chain) that helps bind and regulate the subunits that make up antibodies was evolutionarily co-opted by the human immune system from another biological process, according to a study by researchers from Penn State, the University of Maryland and the University of Chicago. The J chain, shown here in purple, assembles and stabilizes, from left, immunoglobin A (IgA) and immunoglobin M (IgM) antibodies. It is also required to move IgA and IgM across the mucus-producing tissue lining body structures with external exposure, like the intestine, nasal cavity and lungs.
Credit: Ttsz/Getty Images.
The human immune system is a problem for creationists who insist that their putative creator god designed humans perfectly but didn't create pathogenic parasites, which were created later by another creator called 'Sin' because of 'The Fall' after which this 'Sin' thing was free to create everything that increases the suffering in the world, so the question that throws creationists into confusion is when was the human immune system created?
If it was created before 'The Fall' then their designer god was planning for 'The Fall' all along and Adam & Eve had no choice but to comply with this god's plan for them, so there was no disobedience; just compliance with the plan.,
If, on the other hand, the creator had to upgrade its design later to protect its creation from pathogens, then it had failed to anticipate 'The Fall' so can't be omniscient.
And, since pathogens can and do get passed our immune defences, then a perfect, omnipotent creator did not design the immune system because it fails to work as designed, or 'Sin' can outwit it.
And now creationists have another problem, especially those who have been fooled into believing there is evidence of intelligent design to be found in 'irreducibly complex' structures and processes, because the simple biological explanation for such structures and processes is that they are composed of elements that originally evolved for other purposes and were later exapted for a novel function as part of the 'irreducibly complex' structure. For example, almost all the elements of the bacterial flagellum are to be found in the Type III secretion system (T3SS) which bacteria used to bind themselves to their potential host, but motility was such an advantage that the T3SS was repurposed for a flagellum with a few additional proteins and a slight modification of others to improve its efficiency.
Two of the components of the immune system are protein complexes which are the antibodies produced in response to infection by pathogens. These are the immunoglobin M (IgM) and immunoglobin A (IgA). Both these are stabilised by a Joining chain (a short length of protein) called the J chain. And this is the component that was co-opted from an entirely unrelated biological process, as a team of researchers at Penn State University, which included Kazuhiko Kawasaki, associate research professor of anthropology, discovered.
Their research was published a few days ago in Proceeding of the National Academy of Science (PNAS) and is explained in a Penn State University news release:
Biological systems can behave as siblings in several ways, including by borrowing something and never giving it back. That appears to be what the human immune system did with a protein that now helps bind and regulate the subunits that make up antibodies, according to a multi-institute research collaboration. They found that, before the immune system evolutionarily co-opted it, the protein originally belonged to gene family responsible for directing cells to move to the right location at the right time to address specific functional needs.
The researchers, including Kazuhiko Kawasaki, associate research professor of anthropology at Penn State, published their findings in the Proceedings of the National Academy of Sciences. According to the team, while this work primarily informs a fundamental understanding of one feature of the immune system and associated genes, it may also help open design pathways future therapeutics, such as personalized immune responses.
“Everything comes from somewhere, and we believe we found the origin of immunoglobin Joining chain (J chain), an important immune molecule,” said corresponding author Martin F. Flajnik, department of microbiology and immunology, University of Maryland, who led the study. Flajnik also earned his undergraduate degree in biology from Penn State in 1978 before completing his graduate degrees at the University of Rochester.
The J chain assembles and stabilizes two types of antibodies, called immunoglobin M (IgM) and immunoglobin A (IgA). It specifically regulates the structures of the IgM and IgA molecules, which have several subunits, and is required for their movement across the mucus-producing tissue lining body structures with external exposure, like the intestine, nasal cavity and lungs. The researchers found that the J chain originated from the CXCL chemokines, a specific family of proteins that regulate the ability of white blood cells to move throughout the body.
Evolutionarily, new genes are often generated from genes that reside physically close together on the chromosome, and those genes typically remain clustered together even as they evolve different yet similar functions, but Kawasaki said location isn’t the only deciding factor to determine origin.Like immunoglobin itself and human-like adaptive immunity, the J chain emerged in jawed vertebrates, but its origin has remained mysterious since its discovery over 50 years ago. This finding was never anticipated. Chemokine-driven locomotion is a vital function of the immune system, but a totally different function as compared to the J chain!
Martin F. Flajnik, corresponding author
Department of microbiology and immunology,
University of Maryland, Baltimore, MD, USA.
Flajnik said he had a hunch that the J chain was related to a group of secretory calcium-binding phosphoprotein (SCPP) genes due to their similar charges and levels of proline, an amino acid. He knew Kawasaki was an expert on SCPP genes, so he emailed him to assess the idea.The evolutionary relationship of genes can usually be detected when two genes retain similar nucleotide sequences or encoded amino acid sequences, but previous studies could not detect any genes that show sequence similarities to the J chain gene, probably because the J chain gene sequence was quickly changed at its origin.
Kazuhiko Kawasaki, lead author
Department of Anthropology
Pennsylvania State University, University Park, PA, USA
“He told me that, for various good reasons, the SCPPs and J chain were not related,” Flajnik said. “That was sad, as it was my favorite hypothesis.”
However, Kawasaki had noticed that genes on the opposite side of the J chain gene, away from the SCPP genes, did appear to be related to the J chain. Those were the CXCL chemokine genes.
The Joining chain shares three characteristics with the CXCL chemokine genes, including the same number of exons, which encode the protein, and phases of introns, which act as interrupters to stop or start splicing of the RNA molecules transcribed from the gene. The second exon encodes the same sequence, which is known as the classical tripeptide Cysteine-X-Cysteine, for both genes. The lengths of three of the exons are also similar.Credit: Provided by Martin F. Flajnik and Kazuhiko Kawasaki. All Rights Reserved.
“I immediately checked these CXCL chemokine genes and found that, though these genes do not show sequence similarities to the J chain genes, these genes and the J chain gene resemble each other with other various characteristics,” Kawasaki said.
Those characteristics include the same number of exons, which encode the protein, and phases of introns, which act as interrupters to stop or start splicing of the RNA molecules transcribed from the gene. The second exon encodes the same sequence, which is known as the classical tripeptide Cysteine-X-Cysteine, for both genes. The lengths of three of the exons are also similar.
“No other gene encoding the human secretome, which encompasses all proteins that can be secreted by cells of an organism, shares all three characteristics,” Kawasaki said.
The bonds between the Cysteine molecules encoded by the second exon in each gene are completely different from one another, though, the researchers said.
“This means that a chemokine can change its structure, to a large extent, and take on a new function,” Flajnik said.
Next, the researchers said they plan to investigate if chemokines have taken on other functions, specifically in the immune system. They also want to study if chemokines are pliable in their structure, which could indicate the ability to take on an entirely new secondary structure, adapting in response to different biological needs as required.
“I've been around for a long time, for 44 years in science, but this experience was one of the most incredibly satisfying and lucky,” Flajnik said. “I doubt that this similarity would have been uncovered for a long time without the serendipitous interaction between Kazuhiko and me.”
Other co-authors include Yuko Ohta, assistant professor of microbiology and immunology at the University of Maryland, and Caitlin D. Castro, a research fellow in the Department of Biochemistry and Molecular Biology at the University of Chicago.
AbstractYet another biological structure which appears to be irreducibly complex, in that if any component is removed the structure fails, is shown to have evolved by repurposing existing structures, just like the bacterial flagellum evolved. There was no need for all the components to evolve together in a single step because they all pre-existed in other structures that had evolved independently. Evolution simply made use of what was available to it and retained it if it gave a significant advantage.
The joining (J) chain regulates polymerization of multimeric Immunoglobulin(Ig)M and IgA, forming a disulfide bond to the C termini of their Ig heavy chains, and it controls IgM/IgA transport across mucosal epithelia. Like Ig itself and human-like adaptive immunity, J chain emerged in jawed vertebrates (gnathostomes), but its origin has remained mysterious since its discovery over 50 y ago. Here, we show unexpectedly that J chain is a member of the CXCL chemokine family. The J chain gene (JCHAIN) is linked to clustered CXCL chemokine loci in all gnathostomes except actinopterygians that lost JCHAIN. JCHAIN and most CXCL genes have four exons with the same intron phases, including the same cleavage site for the signal peptide/mature protein. The second exon of both genes encodes a CXC motif at the same position, and the lengths of exons 1 to 3 are similar. No other gene in the human secretome shares all of these characteristics. In contrast, intrachain disulfide bonds of the two proteins are completely different, likely due to modifications in J chain to direct Ig polymerization and mucosal transport. Crystal structures of CXCL8 and J chain share a conserved beta-strand core but diverge otherwise due to different intrachain disulfide bonds and extension of the J chain C terminus. Identification of this ancestral affiliation between J chain and CXCL chemokines addresses an age-old problem in immunology.
The adaptive immune system arose 500 Mya in vertebrates (1). Immunoglobulins (Igs) are crucial for human and all gnathostome (jawed vertebrate) immunity. IgM and IgD are primordial Ig isotypes, with IgM being best studied. Upon B cell activation, alternative splicing of IgHeavy(H) chain mRNA causes IgM secretion from plasma cells as multimers, mostly pentamers (2). The joining (J) chain was discovered in 1970 as a component of IgA (3), and IgM (4). It is expressed by most plasma cells, and IgM pentamerization/IgA dimerization is regulated by incorporation of J chain via disulfide bonding with a cysteine (Cys) in the IgH secretory tail (5, 6). J chain is required for transport of Igs across mucosal epithelia, and effector humoral immunity is dysregulated in knockout mice. J chain is present in all gnathostomes except actinopterygians (ray-fins) where it was lost. J chain sequences have never revealed a relationship to any recognized gene family. J chain crystal structure was finally solved in 2020, in association with IgM and IgA (7, 8), which provided an appreciation of its function in polymerization and mucosal transport; however, no insight into J chain origins was uncovered. Herein, we investigated evolutionary emergence of JCHAIN based on conserved synteny and surprising kinship with a major immune superfamily, the CXCL chemokines, which arose in jawless vertebrates (9). We found a strong relationship with these chemokines, likely unmasking J chain’s derivation. In addition to informing the membership of J chain into this chemokine family, we speculate on how a chemokine can be recruited for a new function.
The Unintelligent Designer: Refuting The Intelligent Design Hoax
ID is not a problem for science; rather science is a problem for ID. This book shows why. It exposes the fallacy of Intelligent Design by showing that, when examined in detail, biological systems are anything but intelligently designed. They show no signs of a plan and are quite ludicrously complex for whatever can be described as a purpose. The Intelligent Design movement relies on almost total ignorance of biological science and seemingly limitless credulity in its target marks. Its only real appeal appears to be to those who find science too difficult or too much trouble to learn yet want their opinions to be regarded as at least as important as those of scientists and experts in their fields.
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The Malevolent Designer: Why Nature's God is Not Good
This book presents the reader with multiple examples of why, even if we accept Creationism's putative intelligent designer, any such entity can only be regarded as malevolent, designing ever-more ingenious ways to make life difficult for living things, including humans, for no other reason than the sheer pleasure of doing so. This putative creator has also given other creatures much better things like immune systems, eyesight and ability to regenerate limbs that it could have given to all its creation, including humans, but chose not to. This book will leave creationists with the dilemma of explaining why evolution by natural selection is the only plausible explanation for so many nasty little parasites that doesn't leave their creator looking like an ingenious, sadistic, misanthropic, malevolence finding ever more ways to increase pain and suffering in the world, and not the omnibenevolent, maximally good god that Creationists of all Abrahamic religions believe created everything. As with a previous book by this author, "The Unintelligent Designer: Refuting the Intelligent Design Hoax", this book comprehensively refutes any notion of intelligent design by anything resembling a loving, intelligent and maximally good god. Such evil could not exist in a universe created by such a god. Evil exists, therefore a maximally good, all-knowing, all-loving god does not.
Illustrated by Catherine Webber-Hounslow.
Available in Hardcover, Paperback or ebook for Kindle
Illustrated by Catherine Webber-Hounslow.
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