No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Evolutionary Paradox of Immunity
ResearchGate has not been able to resolve any citations for this publication.
Immunoglobulin and T-cell-receptor genes are assembled from component gene segments in developing lymphocytes by a site-specific recombination reaction, V(D)J recombination. The proteins encoded by the recombination-activating genes, RAG1 and RAG2, are essential in this reaction, mediating sequence-specific DNA recognition of well-defined recombination signals and DNA cleavage next to these signals. Here we show that RAG1 and RAG2 together form a transposase capable of excising a piece of DNA containing recombination signals from a donor site and inserting it into a target DNA molecule. The products formed contain a short duplication of target DNA immediately flanking the transposed fragment, a structure like that created by retroviral integration and all known transposition reactions. The results support the theory that RAG1 and RAG2 were once components of a transposable element, and that the split nature of immunoglobulin and T-cell-receptor genes derives from germline insertion of this element into an ancestral receptor gene soon after the evolutionary divergence of jawed and jawless vertebrates.
Their ability to move within genomes gives transposable elements an intrinsic propensity to affect genome evolution. Non-long terminal repeat (LTR) retrotransposons--including LINE-1, Alu and SVA elements--have proliferated over the past 80 million years of primate evolution and now account for approximately one-third of the human genome. In this Review, we focus on this major class of elements and discuss the many ways that they affect the human genome: from generating insertion mutations and genomic instability to altering gene expression and contributing to genetic innovation. Increasingly detailed analyses of human and other primate genomes are revealing the scale and complexity of the past and current contributions of non-LTR retrotransposons to genomic change in the human lineage.
Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so high that many of the mutations involved must be neutral ones.
The history and evolutionary pathways of defense reactions among various forms of life are reconstructed. The vertebrates evolved step-by-step from their invertebrate ancestors living in the distant past. The ancestry of vertebrate defense mechanisms must be traceable to them because these functions cannot be considered separately from the common evolutionary schema. The first part of this survey is therefore devoted to the description of major defense reactions and achievements in invertebrates. Particular emphasis is given to the taxa of present-day invertebrates most likely to exhibit some relationship to the chordates and thus to show real traces of vertebrate immune patterns. The second part involves three key assemblages of deuterostomate animals--the echinoderms, the nonvertebrate chordates, and the first vertebrates because these animals are believed to have created the prerequisites for transition from the invertebrate type of defense to the vertebrate type of adaptive immunity.
The importance of V(D)J recombination for generating diversity in the immune system is well established, but the mechanisms
which regulate V(D)J recombination are still poorly understood. Although transcription of unrearranged (germ line) immunoglobulin
and T-cell receptor gene segments often precedes V(D)J recombination and has been implicated in its control, the actual role
of germ line transcripts in V(D)J recombination is not known. We used a sensitive reverse transcription-PCR assay to study
immunoglobulin VH germ line transcripts in proB lines from RAG-deficient mice. All 10 VH families analyzed were germ line transcribed, and germ line transcription was found in all of the cell lines examined, indicating
that active chromatin was present in the VHregion. However, not all VH families were germ line transcribed in every cell line, and there was a surprising lack of uniformity in the number and family
distribution of germ line VH transcripts in individual lines. When V(D)J recombination was activated by restoration of RAG activity, recombinational activity
of endogenous VH genes for which germ line transcription was observed could be compared with those of genes for which it was not observed.
This analysis revealed multiple examples of endogenous VH gene segments which were rearranged in cells where their germ line transcription was not detectable prior to RAG expression.
Thus, our data provide strong support for the idea that V-(D)J recombination does not require germ line transcription of the
recombining variable gene segment.
Evolutionary mechanisms of defense reactions Access this article online Quick Response Code: Website: www.najms.org DOI: 10
- V Vìtvièka
- Šíma
Vìtvièka V, Šíma P. Evolutionary mechanisms of defense reactions. Basel, Switzerland: Birkhauser Verlag AG; 1998. Access this article online Quick Response Code: Website: www.najms.org DOI: 10.4103/1947-2714.150090 [Downloaded free from http://www.najms.org on Thursday, February 05, 2015, IP: 136.165.151.140] || Click here to download free Android application for this journal
Evolutionary mechanisms of defense reactions
- V Vìtvièka
- P Šíma
Vìtvièka V, Šíma P. Evolutionary mechanisms of defense
reactions. Basel, Switzerland: Birkhauser Verlag AG; 1998.
Volvox, chlamydomonas, and the evolution of multi cellularity
- S M Miler
Miler SM. Volvox, chlamydomonas, and the evolution of multi
cellularity. Nature Educ 2010;3:65-9.