芬蘭赫爾辛基大學(xué)癌癥研究中心的研究人員在尋找新的腫瘤抑制基因時，發(fā)現(xiàn)了一個重要的進(jìn)化改變,，這個改變發(fā)生在一個關(guān)鍵的發(fā)育信號途徑中，該發(fā)現(xiàn)顯示了復(fù)雜細(xì)胞間信號途徑的一個潛在機制,。
一般,，有少量的進(jìn)化保守基因控制動物物種的多樣性發(fā)育。其中大多數(shù)基因最初主要發(fā)現(xiàn)于果蠅中,，可以根據(jù)對突變體的分析來改變胚胎的發(fā)育模式。
在胚胎發(fā)育期間,，細(xì)胞通過分泌型的胞外信號分子（生長因子或形態(tài)發(fā)生素）來調(diào)節(jié)彼此的生長和分化,，這些分子能綁定其它細(xì)胞的表面受體,。然后將這些細(xì)胞內(nèi)信號途徑受體組成蛋白中轉(zhuǎn)給細(xì)胞核，激活轉(zhuǎn)錄因子,，進(jìn)而影響基因的表達(dá)并誘導(dǎo)細(xì)胞生長和分化,。
大多數(shù)發(fā)育信號途徑的信號轉(zhuǎn)導(dǎo)分子和機制被認(rèn)為是進(jìn)化保守的，由于缺乏過渡類型,，這些復(fù)雜信號途徑在進(jìn)化細(xì)節(jié)上還不清楚,。
由于Hedgehog（Hh）信號途徑在人類癌腫中沒有發(fā)現(xiàn)，研究人員為不如動物克隆了一個果蠅的關(guān)鍵Hh信號途徑調(diào)節(jié)因子——Costal-2,。然而,，對哺乳動物基因功能作進(jìn)一步分析則顯示出它并沒有像Hh信號途徑一樣的功能，更不用說像腫瘤抑制基因一樣了,。
不過,，研究人員發(fā)現(xiàn)在果蠅的Hh信號途徑中具有微小作用的另一個基因（啟動抑制子）對于哺乳動物Hh信號途徑的調(diào)節(jié)來說非常重要。
該發(fā)現(xiàn)首次解釋闡明了在不同物種間的主要保守信號途徑,，這將有助于解釋進(jìn)化生物學(xué)中復(fù)雜的信號途徑,。
By University of Helsinki, Cancer researchers at the University of Helsinki, in trying to find a novel tumor suppressor gene, instead found an important evolutionary change that occurred in a key developmental signalling pathway. The finding suggests a potential mechanism for evolution of complex intercellular signalling pathways.
A relatively small number of evolutionary conserved genes are responsible for controlling the development of the diverse range of animal species. Most of these genes have been originally identified in fruit fly, based on the analysis of mutations that alter the body pattern of a developing embryo.
During embryonic development, cells regulate the growth and differentiation of each other by secreting extracellular signalling molecules (growth factors or morphogens), which bind to receptors present on the surface of other cells. The receptors in turn activate intracellular signalling pathway composed of proteins that relay the signal to the nucleus, activating specialized proteins called transcription factors. The transcription factors then affect expression of genes that induce cell growth and differentiation.
The signal transduction molecules and mechanisms of major developmental signalling pathways are thought to be evolutionary conserved between invertebrates and vertebrates in such a way that if a signalling pathway is present in a given organism, it includes all the major classes of components found in humans. Because of the lack of intermediate forms, the evolution of these complex signalling pathways is not understood in detail, and the emergence of signalling pathways with multiple specific and essential components has even been used as an argument against evolution.
Because multiple components of the Hedgehog (Hh) signalling pathway are defective in human cancers, Markku Varjosalo in Professor Jussi Taipale's laboratory (the University of Helsinki and National Public Health Institute of Finland) cloned the gene for mammalian homolog of a key regulator of fruit fly Hh signalling pathway, Costal-2. However, further analysis of the function of the mammalian gene revealed that it did not function as a Hh pathway regulator, let alone as the tumor suppressor gene the researchers had hoped for. Instead, together with a group led by Prof. Rune Toftg錼d and Dr. Stephan Teglund from Karolinska Institutet, the researchers found that another gene (Suppressor of Fused), which has a minor role in Hh signalling in fruit fly is critical for Hh pathway regulation in mammals.
The finding is the first clear demonstration of a major difference in the function of conserved signalling pathways between species. The results also show that multi-component pathways evolve, in part, by the insertion of novel proteins between existing pathway components. This insertion mechanism can potentially explain a challenging aspect of evolutionary biology regarding the emergence of signalling pathways with multiple specific components.
- Developmental Cell Journal
原文見：http://www.rxpgnews.com/research/embryology/article_3377.shtml
