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  Topic: immune system evolution, collecting references to recent articles< Next Oldest | Next Newest >  

Posts: 319
Joined: May 2002

(Permalink) Posted: Mar. 31 2003,22:46   

Since this came up again with the discussion with Nelson Alonso on the ISCID thread, I just came across a review of a recent workshop on evolutionary immunology.  I quote the bit about the origin of recombining receptors:


Dev Comp Immunol 2003 Apr;27(4):263-71
Workshop report: evolutionary immunobiology--new approaches, new paradigms.

Du Pasquier L, Smith LC.


3. The boundary between invertebrates and vertebrates
Those working on innate immunity and who are impressed by the efficiency of these defense mechanisms frequently ask, "why did vertebrates acquire an adaptive immune system that was based on somatic rearrangement?" The multiplicity and diversity of the innate systems described above may provide the beginnings of an answer to this question. If an animal like Drosophila, which lives for a relatively short time, requires many germ line encoded innate mechanisms to survive, how many mechanisms will be required for the survival of long lived species? At some point during metazoan evolution, an increase in the number of genes devoted to innate immunity would have been required. Rather than an amplification of genetic material devoted to immune defenses becoming detrimental, the introduction of a somatic mechanism to generate a repertoire of recognition structures resulted in an economy or at least a status quo in the amount of the genome that was devoted to immune responsiveness. At the same time a somatic mechanism providing in fact a `kit' to generate one's repertoire by oneself would probably be favored by species producing few offspring where the value of a single individual would be very important. Therefore it would not be that surprising that phyla other than vertebrates have invented (by means that could be different from those of the vertebrates) a somatic way of increasing the diversity of their receptors (e.g. see the above mentioned possibilities of alternate RNA processing and splicing). Today, one of the striking paradoxes of the evolution of the combinatorial immune system is that RAG homologues appear to be totally lacking in the lower deuterostomes and in all non-deuterostome metazoans. This suggests a rapid evolutionary emergence and phylogenetic restriction for the capacity to generate specific inducible immunity in higher vertebrates. This implies that the introduction of the rearranging machinery occurred in a gene encoding a receptor that was already committed to expression in a lymphocyte-like cell, and perhaps involved in innate immune defense mechanisms. Therefore, to understand this major evolutionary step, a search is under way for the origin of the lymphocyte lineage and for an Ig superfamily (IgSf) gene target which may be similar to a T-cell receptor or an immunoglobulin gene. The animals used in these searches include modern members of classes that preceded the gnathostomes in evolution.

Michele Anderson (Pasadena) presented information on transcription factors involved in hematopoiesis and the definition of lymphoid lineages. If diversity was a master theme during this workshop, conservation of patterns was another and not only for the Toll cascade. A good example is the conservation of patterns (in structure, function and pathways) of transcription factors. Anderson discussed her investigations of skates, lampreys, amphioxus and sea urchins, and searches for homologues of transcription factors important in hematopoiesis. She has been monitoring the Ikaros/Aiolos/Helios family, PU.1, and GATA-1/2/3 families of transcription factors, all of which include essential or important factors in lymphoid development. In the clear nose skate (Raja eglanteria, a species that is also suitable for developmental studies), the existence of EBF, GATA3, members of the Ikaros family, and PU.1, are all consistent with the finding of Ig and TCR genes expressed at this level of vertebrate phylogeny. Expression of the transcription factor, Spi-C, appeared to be specific to the spleen and therefore, may be involved with B cell development. It was assumed that multiple members of each transcription factor family found in the elasmobranchs arose by gene duplication from a less complex population of progenitor genes. In invertebrates the number of homologues found so far fits with this hypothesis: fewer in the invertebrates and increased gene family sizes in higher vertebrates. For example, PU.1 and Spi-C are not found in the Drosophila genome, while one member of the PU.1 family is found in the lamprey, even though no classical adaptive immune system has been characterized in this species. Based on the sequence of the lamprey GATA gene, it appears to encode a pre-duplication molecule with GATA 2/3 features. The existence of PU.1 and GATA-1/2/3 family transcription factors in the lamprey, a jawless vertebrate, suggests that the stage was set for lineage-specific expression of certain antigen receptors just prior to the introduction of RAG-1 and RAG-2 in the earliest jawed vertebrates. Anderson stressed the importance of the cis-acting elements that control the expression of the duplicated GATA genes and orient them in different patterns of expression. She also warned us about terminology in this field and about the difficulty of identifying orthologues. The workshop participants discussed and agreed upon the need for a strong gene ontology if highly diverse systems are to be compared fruitfully.

Still within the context of transcription factors, Jack Marchalonis (Tucson) described the lamprey vitamin D receptor (VDR), a ligand-specific transcription factor that is a member of the Nuclear Receptor Superfamily (NRS), which has been cloned from `protospleen' cDNA of the larval stage. In mammals, the VDR is a transcription factor that mediates the actions of its ligand, vitamin D, and can promote monocyte/macrophage differentiation and inhibit proliferation and cytokine production by activated T lymphocytes. These functions make the VDR relevant and interesting for innate immunity. Like VDRs of jawed vertebrates, the lamprey molecule consists of two C4-type zinc fingers, and both DNA-binding segments and ligand-binding segments show significant conservation across species. Cladograms of the NRS family, using the ecdysone receptor of insects as an outgroup (a distantly related member of this gene family) indicated that the lamprey VDR clustered unambiguously with the other vertebrate VDRs and constituted the basal member of the group.

Marchalonis (Tucson) also commented on the complete characterization of the RAG1/RAG2 gene cluster in the sandbar shark and the evolutionary and functional implications of this analysis. The ancestors of the sharks were apparently the first vertebrates in phylogeny to have acquired RAG genes which have been highly conserved during evolution both in terms of sequence and gene organization. In common with other vertebrate species, the shark RAG2 coding region lacks introns and is closely linked in opposite orientation to the RAG1 gene. The intergenic region (~10 kb) is comparable in length to that of tetrapods. About 40% of the spacer consists of SINE and LINE fragments homologous to those found in other sharks, reptiles and birds.

(the bit about the regulation of lamprey receptors is key...)

In the conclusion the old theme of change-of-function is emphasized:


At the heart of it, we are attempting to understand the dynamics of complex systems by comparative methods. For example, are there common threads in the metabolic machinery from one system to another? Clearly there must be, as one of the themes of this conference was the adaptation of pre-existing molecules and metabolic pathways to new functions. Likewise, are there common features of the immune (or other metabolic) system that can be extracted and used to understand more fully the evolution of immunity and organisms? This field has become known as phylogenomics. Further, the response of an organism to environmental change is equivalent in concept to immune responses to invading organisms. Does it really matter whether the environmental challenge is a pathogen or an elevation in temperature? The organism will respond to environmental changes that alter metabolic functions. The application of genomic tools to the study of ecosystems, ecogenomics, is an emerging discipline dedicated to this end and owes much to developments in immunology. We are very familiar with the common features in ecosystems of primary producers, herbivores, carnivores and decomposers which circumscribes the flow of energy and mass through the system. In phylogenetics, there are accepted hierarchies in vertebrate groups, and some invertebrates as well, which are assumed to reflect the ancestor–descendent relationships (i.e. flow of genetic material over time). However, similar unifying principles and classification schemes are completely lacking in studies of cellular mechanisms except where individual components are concerned (e.g. the TCA cycle). Hence, the concepts developed in a systems approach to immune function can cut across a wide range of biological studies and mathematical tools are needed to exploit these data.

...this last bit seems to be saying that understanding the evolution of a complex system is much easy when you have a good phylogenetic understanding of the system (as with the immune system) than when you don't (e.g. most of Behe's IC systems, which originated in single-celled organisms).

  23 replies since Dec. 17 2002,18:45 < Next Oldest | Next Newest >  


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