癌基因的远古起源：与后生动物的多细胞化相关

sunsong7

德国莱科学家通过追踪某一基因的祖先来追溯该基因的源头，接着确定该基因的最小年龄，发现遗传疾病主要影响地球生命最初出现时的细胞过程：大多数这些疾病基因可以追溯到第一个细胞那里，其它大群的基因出现在10亿年以前———此时，多细胞有机体首次出现。而且，没有疾病同一些哺乳动物产生后出现的基因有关。
$ x0 e+ T- j# C2 h, d9 ]# C最近发现癌基因与后生动物的多细胞化相关联：
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& e2 P" S3 _6 A; OPhylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa
8 [) Q- ^$ t- }Tomislav Domazet-Lošo1,2  and Diethard Tautz1 , i) X; T& Z0 E6 B6 o
1  Max-Planck Institut für Evolutionsbiologie, August-Thienemannstrasse 2, 24306 Plön, Germany
7 z' @! k' V, k9 v9 D' R2  Laboratory of Evolutionary Genetics, Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, PP 180, 10002 Zagreb, Croatia
6 M9 c2 y2 z& y( F6 s& NBMC Biology 2010, 8:66doi:10.1186/1741-7007-8-666 H& n" B- v8 @$ S$ O0 [
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Abstract( y  Q9 @1 ~3 t2 W
Background. u# `- y/ {: ]& q9 d
Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains) of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity.; P3 }! \5 U  C: w. B8 _

+ m$ [6 {% G! ?! fResults
' M. {+ g' t0 xWe find two strong peaks of the emergence of cancer related protein domains, one at the time of the origin of the first cell and the other around the time of the evolution of the multicellular metazoan organisms. These peaks correlate with two major classes of cancer genes, the 'caretakers', which are involved in general functions that support genome stability and the 'gatekeepers', which are involved in cellular signalling and growth processes. Interestingly, this phylogenetic succession mirrors the ontogenetic succession of tumour progression, where mutations in caretakers are thought to precede mutations in gatekeepers.  ]- `  d  r3 j3 E
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Conclusions4 p/ t% @" ~. t9 L+ c# b
A link between multicellularity and formation of cancer has often been predicted. However, this has not so far been explicitly tested. Although we find that a significant number of protein domains involved in cancer predate the origin of multicellularity, the second peak of cancer protein domain emergence is, indeed, connected to a phylogenetic level where multicellular animals have emerged. The fact that we can find a strong and consistent signal for this second peak in the phylostratigraphic map implies that a complex multi-level selection process has driven the transition to multicellularity.
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http://www.biomedcentral.com/1741-7007/8/66/abstract
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