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(shí)，發(fā)現(xiàn)了一個(gè)重要的進(jìn)化改變，這個(gè)改變發(fā)生在一個(gè)關(guān)鍵的發(fā)育信號(hào)途徑中,，該發(fā)現(xiàn)顯示了復(fù)雜細(xì)胞間信號(hào)途徑的一個(gè)潛在機(jī)制,。
一般，有少量的進(jìn)化保守基因控制動(dòng)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(duì)突變體的分析來(lái)改變胚胎的發(fā)育模式。
在胚胎發(fā)育期間,，細(xì)胞通過(guò)分泌型的胞外信號(hào)分子（生長(zhǎng)因子或形態(tài)發(fā)生素）來(lái)調(diào)節(jié)彼此的生長(zhǎng)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(hào)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(zhǎng)和分化。
大多數(shù)發(fā)育信號(hào)途徑的信號(hào)轉(zhuǎn)導(dǎo)分子和機(jī)制被認(rèn)為是進(jìn)化保守的,，由于缺乏過(guò)渡類型,，這些復(fù)雜信號(hào)途徑在進(jìn)化細(xì)節(jié)上還不清楚。
由于Hedgehog（Hh）信號(hào)途徑在人類癌腫中沒(méi)有發(fā)現(xiàn),，研究人員為不如動(dòng)物克隆了一個(gè)果蠅的關(guān)鍵Hh信號(hào)途徑調(diào)節(jié)因子——Costal-2,。然而，對(duì)哺乳動(dòng)物基因功能作進(jìn)一步分析則顯示出它并沒(méi)有像Hh信號(hào)途徑一樣的功能,，更不用說(shuō)像腫瘤抑制基因一樣了,。
不過(guò)，研究人員發(fā)現(xiàn)在果蠅的Hh信號(hào)途徑中具有微小作用的另一個(gè)基因（啟動(dòng)抑制子）對(duì)于哺乳動(dòng)物Hh信號(hào)途徑的調(diào)節(jié)來(lái)說(shuō)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(hào)途徑,，這將有助于解釋進(jìn)化生物學(xué)中復(fù)雜的信號(hào)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(jiàn)：http://www.rxpgnews.com/research/embryology/article_3377.shtml
