Mutations & structural modifications - Redux

The homeobox is just another type of DNA binding domain like bHLHs, Zn Fingers or Leucine zippers. It is some of the weird aspects of the HOX cluster whose origins are most obscure, such as where did the clusters spatial and temporal colinearity arise from?As to work on the ancestral HOX genes, I have a reference which constructs possible sequences for them, and finds them to have no strong relation to any particular modern HOX group, but I cant get the full text online.Kourakis MJ, Martindale MQ. Combined-method phylogenetic analysis of Hox and ParaHox genes of the metazoa.
J Exp Zool. 2000 Aug 15;288(2):175-91. http://www.ncbi.nlm.nih.gov:80......
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Hi WK,
I went to the link and clicked on full version pdf and I managed to access the full text version. Did you try that? The full text HTML version link was dead.Hopefully I will get some time to read the article today...cant promise though...muskoxen and mammoths are keeping me busy today

My University Library doesnt appear to subscribe to that particular Journal online, ho hum.I notice that despite my best intentions almost all of this thread is now taken up with us discussing the Hox genes, dammit!!

As I am the culpable party I will desist in bringing up Hox genes....and as a peace offering the following recent non-Hox gene which has a large phenotypic effectNat Genet 2003 Jun;34(2):203-8Fraser syndrome and mouse blebbed phenotype caused by mutations in FRAS1/Fras1 encoding a putative extracellular matrix protein.McGregor L, Makela V, Darling SM, Vrontou S, Chalepakis G, Roberts C, Smart N, Rutland P, Prescott N, Hopkins J, Bentley E, Shaw A, Roberts E, Mueller R, Jadeja S, Philip N, Nelson J, Francannet C, Perez-Aytes A, Megarbane A, Kerr B, Wainwright B, Woolf AS, Winter RM, Scambler PJ.Molecular Medicine, Institute of Child Health, London WC1N 1EH, UK.Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero.

An interesting example of a structural change associated with a change in the timing, but not the location, of gene expression. Changes in the coordination of two periods of Scute expression lead to a change of machrochaete to microchaete in Phormia terranovae.Skaer N, Pistillo D, Simpson P.
Transcriptional heterochrony of scute and changes in bristle pattern between two closely related species of blowfly.
Dev Biol. 2002 Dec 1;252(1):31-45.

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Temporal shifts in the expression of regulatory genes, relative to other events taking place during development, can result in changes in morphology. Such transcriptional heterochrony can introduce dramatic morphological changes that involve rather few genetic events and so has the potential to cause rapid changes during evolution. We have shown previously that stereotyped species-specific bristle patterns on the notum of higher Diptera correlate with changes in the spatial regulation of scute expression. scute encodes a proneural gene required for the development of sensory bristle precursors and is expressed before pupation in discrete domains on the presumptive notum at sites where the macrochaete precursors arise. Thus, for Ceratitis capitata and Calliphora vicina, species separated from Drosophila melanogaster by about 80 and 100 million years respectively, the domains of sc expression differ. In all three species, a second phase of ubiquitous sc expression, after pupation, precedes formation of the microchaete precursors. Here, we describe sc expression in Phormia terranovae, a species belonging to the family Calliphoridae that is closely related to C. vicina. We find that spatial regulation is almost identical between P. terranovae and C. vicina, in spite of their different bristle patterns. The timing of sc expression differs, however, between the two. The first spatially restricted phase of expression is slightly delayed and the second ubiquitous phase remarkably accelerated, such that there is a period of overlap. As a result, the last precursors from the first phase of expression arise at the same time as the first precursors from the second phase of expression and are morphologically indistinguishable from the late-arising microchaetes. These observations illustrate the power of developmental heterochrony in bringing about rapid morphological change.

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http://www.ncbi.nlm.nih.gov:80......
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Wounded King couldn't track down this topic, so he started a new one, "Morphology and mutation".I'm bringing in the following (posted by Wounded King), and closing that other topic.

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A previous thread on mutations leading to structural changes in an organism seems to have dropped off the end of this Forum. I was going to add this particular example to it.

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Trends Genet. 2003 May;19(5):248-52.

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The callipyge locus: evidence for the trans interaction of reciprocally imprinted genes.

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Georges M, Charlier C, Cockett N.

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The callipyge phenotype in sheep is an inherited muscular hypertrophy that affects only heterozygous individuals who receive the CLPG mutation from their father. The CLPG mutation is a single nucleotide substitution in what is probably a long-range control element (LRCE) within the DLK1-GTL2 imprinted domain. Recent results suggest that the unique mode of inheritance of callipyge, referred to as polar overdominance, results from the combination of the cis-effect of the CLPG mutation on the expression levels of genes in the DLK1-GTL2 imprinted domain, and the trans interaction between the products of reciprocally imprinted genes.

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this paper is also interesting in that the mutation is regulated by imprinting and shows that epigenetic factors can have considerable influence on phenotype.

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Adminnemooseus------------------
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Here is a paper fresh off the presses that might be of interest to WK and for this thread...Nature 424, 1061 - 1065 (28 August 2003); doi:10.1038/nature01872Cephalopod Hox genes and the origin of morphological noveltiesPATRICIA N. LEE1,2, PATRICK CALLAERTS3, HEINZ G. DE COUET1 & MARK Q. MARTINDALE21 Department of Zoology, University of Hawaii at Manoa, 2538 McCarthy Mall, Honolulu, Hawaii 96822, USA
2 Kewalo Marine Laboratory/Pacific Biomedical Research Center, University of Hawaii, 41 Ahui Street, Honolulu, Hawaii 96813, USA
3 Department of Biology & Biochemistry, University of Houston, 369 Science and Research Bldg 2, Houston, Texas 77204, USACorrespondence and requests for materials should be addressed to H.G.d.C. (couet@hawaii.edu).Cephalopods are a diverse group of highly derived molluscs, including nautiluses, squids, octopuses and cuttlefish. Evolution of the cephalopod body plan from a monoplacophoran-like ancestor entailed the origin of several key morphological innovations contributing to their impressive evolutionary success. Recruitment of regulatory genes, or even pre-existing regulatory networks, may be a common genetic mechanism for generating new structures. Hox genes encode a family of transcriptional regulatory proteins with a highly conserved role in axial patterning in bilaterians; however, examples highlighting the importance of Hox gene recruitment for new developmental functions are also known. Here we examined developmental expression patterns for eight out of nine Hox genes in the Hawaiian bobtail squid Euprymna scolopes, by whole-mount in situ hybridization. Our data show that Hox orthologues have been recruited multiple times and in many ways in the origin of new cephalopod structures. The manner in which these genes have been co-opted during cephalopod evolution provides insight to the nature of the molecular mechanisms driving morphological change in the Lophotrochozoa, a clade exhibiting the greatest diversity of body plans in the Metazoa.