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Author | Topic: Mutations & structural modifications - Redux | |||||||||||||||||||||||
Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
There was a previous thread on this topic which was derailed due to ontological argument. I have a particular interest in this topic so I would like to see it revived.
The original post was on the topic of polydactyly but I would like to widen the remit to all gross structural changes. So what sources have been found for structural change? Single nucleotide mutations? Indels? Gene duplications? Chromosomal rearrangements? Whole genome duplications? How significant are each of these types of mutation in evolutionary terms? Any and all examples would be welcome. What non lethal mutations in humans lead to the loss or gain of an organ? What mutations lead to changes in organ/limb character? One thing I would like to avoid is dwelling on HOX genes, brilliant as they are, a few examples would be great but I don't want to get swamped by homeotic mutant flies and syndactylys.
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
Having said I wanted to avoid HOX examples I now want to post one.
This is an example of a hindbrain patterning defect in Hoxa1 null mice. Rhombomeres 3 and 4 lose character but develop into a novel neural structure which can regulate breathing, although poorly. The mutants are post-natally lethal. del Toro ED, Borday V, Davenne M, Neun R, Rijli FM, Champagnat J. Generation of a novel functional neuronal circuit in Hoxa1 mutant mice.J Neurosci. 2001 Aug 1;21(15):5637-42.
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
Protein family evolution is fascinating stuff, but I think that there is so much of it that it should really have a thread of its own. As you say the gross morphology linked mutations are not as established and lack the wealth of data available to discussions on protein evolution. Consequently I suspect that the structural mutations might be swamped by the protein evolution.
It goes without saying that pretty much all of the mutations affecting gross morphology are down to changes in either protein structure or expression, at least those we know of at the moment. So certain aspects of that are certainly going to be germane, however I think a general discussion of protein structure would deserve its own thread.
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
This paper ascribes the degeneration of the eye primordium to differences in Pax-6 expression. Suggesting that the major difference is either upstream in the signalling pathway or in the regulatory elements of the Pax-6 gene.
Strickler AG, Yamamoto Y, Jeffery WR.Early and late changes in Pax6 expression accompany eye degeneration during cavefish development. Dev Genes Evol. 2001 Mar;211(3):138-44.
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
Is there a specific morphological change that the Evx genes are being proposed to regulate Mammuthus? Are the duplications, seen in both cephalochordate and vertebrate lineages, linked to specific mnorphological changes themselves or do they simply provide a spare copy of the gene upon which natural selection can work to produce a distinct gene. Is there anything known about the effects of overexpression of even skipped or its homologues?
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
Doesnt it almost go without saying that no currently extant species is ancestral to any other? That doesnt mean that the single Hox cluster of amphioxus cannot inform our views on the ancestral hox cluster, as does that of drosophila.
There are quite a few instances of duplicate genes in amphioxus which are related to duplicated genes in vertebrates but appear to be independent, the AmphiEmxs and Amphioxus myogenic regulatory genes for example. I prefer this example from Ciona where one gene has two splice variants with properties similiar to two related proteins in vertebrates. Meedel TH, Farmer SC, Lee JJ.The single MyoD family gene of Ciona intestinalis encodes two differentially expressed proteins: implications for the evolution of chordate muscle gene regulation. Development. 1997 May;124(9):1711-21. http://www.ncbi.nlm.nih.gov:80...{Shortened display form of URL, to restore page width to normal - AM} [This message has been edited by Adminnemooseus, 06-03-2003]
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
It depends what you mean by HOX. If you mean the Genes in the Hox cluster specifically then no there are no obvious homologues that I am aware of in yeast. There are certainly homeobox proteins found in Yeast, fungi and plants.
The origin of the HOX cluster itself is somewhat obscure as you say. They are plentiful in the basal metazoa however and the devlopment of the HOX cluster has been suggested as a major contributor to the cambrian explosion. The cnidaria are probably the most studied basal group. Yanze N, Spring J, Schmidli C, Schmid V.Conservation of Hox/ParaHox-related genes in the early development of a cnidarian. Dev Biol. 2001 Aug 1;236(1):89-98. Slightly further up though there is a lot of work on the nematodes especially C. elegans. Aboobaker AA, Blaxter ML.Hox Gene Loss during Dynamic Evolution of the Nematode Cluster. Curr Biol. 2003 Jan 8;13(1):37-40. Van Auken K, Weaver DC, Edgar LG, Wood WB.Caenorhabditis elegans embryonic axial patterning requires two recently discovered posterior-group Hox genes. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4499-503. Just a moment... Here is a paper hot off the presses touching on the character of the protohox cluster before its split into the HOX and paraHOX clusters. Minguillon C, Garcia-Fernandez J.Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters. Genome Biol. 2003;4(2):R12. Application Unavailable | Springer Nature
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
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......{Shortened display form of URL, to restore page width to normal - AM} [This message has been edited by Adminnemooseus, 06-06-2003]
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
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!!
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Wounded King Member Posts: 4149 From: Cincinnati, Ohio, USA Joined: |
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. quote: http://www.ncbi.nlm.nih.gov:80......{Shortened display form of URL, to restore page width to normal - AM} [This message has been edited by Wounded King, 06-06-2003] [This message has been edited by Adminnemooseus, 06-06-2003]
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