【求助】紧急求助,请问假基因也能表达吗
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假基因是没有功能的基因,要说应该不能表达才是,可为什么有的文献说某某假基因的表达可以影响某某疾病呐?
比如,在Pubmeb上看到假基因pseudogene的表达可以影响前列腺癌的发病
pseudogene与processed pseudogene是一回事吗
比如,在Pubmeb上看到假基因pseudogene的表达可以影响前列腺癌的发病
pseudogene与processed pseudogene是一回事吗
能否把文章发上来大家一起看啊?因为你这样说没有证据战友们无从下手啊。理论上来说,pseudogene与processed pseudogene是一回事。
哪位朋友帮忙啊
zhujoker wrote:
能否把文章发上来大家一起看啊?因为你这样说没有证据战友们无从下手啊。理论上来说,pseudogene与processed pseudogene是一回事。
我不会贴文章
pls read the following text cited from internet. It is very interesting I think.
" By definition, pseudogenes lack a function. However, the classification of pseudogenes generally relies on computational analysis of genomic sequences using complex algorithms.This has led to the incorrect identification of pseudogenes. For example the functional, chimeric gene jingwei in Drosophila was once thought to be a processed pseudogene."
" Types and origin of pseudogenes:
There are three main types of pseudogenes, all with distinct mechanisms of origin and characteristic features. The classifications of pseudogenes are as follows:
1. Processed (or retrotransposed) pseudogenes. In higher eukaryotes, particularly mammals, retrotransposition is a fairly common event that has had a huge impact on the composition of the genome. For example, somewhere between 30% - 44% of the human genome consists of repetitive elements such as SINEs and LINEs (see retrotransposons). In the process of retrotransposition, a portion of the mRNA transcript of a gene is spontaneously reverse transcribed back into DNA and inserted into chromosomal DNA. Although retrotransposons usually create copies of themselves, it has been shown in an in vitro system that they can create retrotransposed copies of random genes, too.Once these pseudogenes are inserted back into the genome, they usually contain a poly-A tail, and usually have had their introns spliced out; these are both hallmark features of cDNAs. However, because they are derived from a mature mRNA product, processed pseudogenes also lack the upstream promoters of normal genes; thus, they are considered "dead on arrival", becoming non-functional pseudogenes immediately upon the retrotransposition event. However, occasionally these insertions contribute exons to existing genes and usually via alternatively spliced transcripts. A further characteristic of processed pseudogenes is common truncation of the 5' end relative to the parent sequence, which is a result of the relatively non-processive retrotransposition mechanism that creates processed pseudogenes.
2. Non-processed (or duplicated) pseudogenes. Gene duplication is another common and important process in the evolution of genomes. A copy of a functional gene may arise as a result of a gene duplication event and subsequently acquire mutations that cause it to become nonfunctional. Duplicated pseudogenes usually have all the same characteristics of genes, including an intact exon-intron structure and promoter sequences. The loss of a duplicated gene's functionality usually has little effect on an organism's fitness, since an intact functional copy still exists. According to some evolutionary models, shared duplicated pseudogenes indicate the evolutionary relatedness of humans and the other primates.
3. Disabled genes, or unitary pseudogenes. Various mutations can stop a gene from being successfully transcribed or translated, and a gene may become nonfunctional or deactivated if such a mutation becomes fixed in the population. This is the same mechanism by which non-processed genes become deactivated, but the difference in this case is that the gene was not duplicated before becoming disabled. Normally, such gene deactivation would be unlikely to become fixed in a population, but various population effects, such as genetic drift, a population bottleneck, or in some cases, natural selection, can lead to fixation. The classic example of a unitary pseudogene is the gene that presumably coded the enzyme L-gulono-γ-lactone oxidase (GULO) in primates. In all mammals studied besides primates (except guinea pigs), GULO aids in the biosynthesis of Ascorbic acid (vitamin C), but it exists as a disabled gene (GULOP) in humans and other primates.[13][14] Another interesting and more recent example of a disabled gene, which links the deactivation of the caspase 12 gene (through a nonsense mutation) to positive selection in humans.
Pseudogenes can complicate molecular genetic studies. For example, a researcher who wants to amplify a gene by PCR may simultaneously amplify a pseudogene that shares similar sequences. This is known as PCR bias or amplification bias. Similarly, pseudogenes are sometimes annotated as genes in genome sequences.
Processed pseudogenes often pose a problem for gene prediction programs, often being misidentified as real genes or exons. It has been proposed that identification of processed pseudogenes can help improve the accuracy of gene prediction methods.
It has also been shown that the parent sequences that give rise to processed pseudogenes lose their coding potential faster than those giving rise to non-processed pseudogenes."
" By definition, pseudogenes lack a function. However, the classification of pseudogenes generally relies on computational analysis of genomic sequences using complex algorithms.This has led to the incorrect identification of pseudogenes. For example the functional, chimeric gene jingwei in Drosophila was once thought to be a processed pseudogene."
" Types and origin of pseudogenes:
There are three main types of pseudogenes, all with distinct mechanisms of origin and characteristic features. The classifications of pseudogenes are as follows:
1. Processed (or retrotransposed) pseudogenes. In higher eukaryotes, particularly mammals, retrotransposition is a fairly common event that has had a huge impact on the composition of the genome. For example, somewhere between 30% - 44% of the human genome consists of repetitive elements such as SINEs and LINEs (see retrotransposons). In the process of retrotransposition, a portion of the mRNA transcript of a gene is spontaneously reverse transcribed back into DNA and inserted into chromosomal DNA. Although retrotransposons usually create copies of themselves, it has been shown in an in vitro system that they can create retrotransposed copies of random genes, too.Once these pseudogenes are inserted back into the genome, they usually contain a poly-A tail, and usually have had their introns spliced out; these are both hallmark features of cDNAs. However, because they are derived from a mature mRNA product, processed pseudogenes also lack the upstream promoters of normal genes; thus, they are considered "dead on arrival", becoming non-functional pseudogenes immediately upon the retrotransposition event. However, occasionally these insertions contribute exons to existing genes and usually via alternatively spliced transcripts. A further characteristic of processed pseudogenes is common truncation of the 5' end relative to the parent sequence, which is a result of the relatively non-processive retrotransposition mechanism that creates processed pseudogenes.
2. Non-processed (or duplicated) pseudogenes. Gene duplication is another common and important process in the evolution of genomes. A copy of a functional gene may arise as a result of a gene duplication event and subsequently acquire mutations that cause it to become nonfunctional. Duplicated pseudogenes usually have all the same characteristics of genes, including an intact exon-intron structure and promoter sequences. The loss of a duplicated gene's functionality usually has little effect on an organism's fitness, since an intact functional copy still exists. According to some evolutionary models, shared duplicated pseudogenes indicate the evolutionary relatedness of humans and the other primates.
3. Disabled genes, or unitary pseudogenes. Various mutations can stop a gene from being successfully transcribed or translated, and a gene may become nonfunctional or deactivated if such a mutation becomes fixed in the population. This is the same mechanism by which non-processed genes become deactivated, but the difference in this case is that the gene was not duplicated before becoming disabled. Normally, such gene deactivation would be unlikely to become fixed in a population, but various population effects, such as genetic drift, a population bottleneck, or in some cases, natural selection, can lead to fixation. The classic example of a unitary pseudogene is the gene that presumably coded the enzyme L-gulono-γ-lactone oxidase (GULO) in primates. In all mammals studied besides primates (except guinea pigs), GULO aids in the biosynthesis of Ascorbic acid (vitamin C), but it exists as a disabled gene (GULOP) in humans and other primates.[13][14] Another interesting and more recent example of a disabled gene, which links the deactivation of the caspase 12 gene (through a nonsense mutation) to positive selection in humans.
Pseudogenes can complicate molecular genetic studies. For example, a researcher who wants to amplify a gene by PCR may simultaneously amplify a pseudogene that shares similar sequences. This is known as PCR bias or amplification bias. Similarly, pseudogenes are sometimes annotated as genes in genome sequences.
Processed pseudogenes often pose a problem for gene prediction programs, often being misidentified as real genes or exons. It has been proposed that identification of processed pseudogenes can help improve the accuracy of gene prediction methods.
It has also been shown that the parent sequences that give rise to processed pseudogenes lose their coding potential faster than those giving rise to non-processed pseudogenes."
现在发现一些假基因是有功能的,不是新鲜事了。
之前测序时也碰到过pseudogene,很麻烦的东西,只有找真基因和假基因的差异处酶切回收后测序。相对来说我这个算是小case啦,要是做mRNA表达分析假基因可就是大麻烦啦。
pseudogene的研究主要以processed pseudogene为主,各种争论五花八门,至少到今天为止还没有一篇能站住脚的文献论证假基因是真正有功能的(Toshiaki Watanabe和ERIC.J.DEVOR分别报道过假基因能能包含着microRNA母本,不知道这算不算是有功能)。另外一些学者们推测pseudogene可以稳定其真基因的mRNA甚至可以调控翻译,但都没有明确的证据。
03年,Shinji Hirotsune研究成果在Nature发表,称“假基因可以调控其真基因的mRNA稳定性”,06年Todd A. Gray的PNAS文章提出质疑,他们发现之前的假基因被高度甲基化——既不表达也不稳定其真基因的mRNA。就这个问题,Jeannie T. Lee、Adam Pavlicek、Satoko Kaneko先后撰文做过探讨,但他们都是比较支持假基因有功能的。
04年,Harish V. Pai在JBC撰文发现假基因CYP2D7P1突变能回复功能,并产生编码蛋白。05年JANELLE M. HOSKINS指出他们研究成果可能是由于实验产生的假阳性造成的。
另外,假基因在干细胞领域也比较受关注,因为OCT-4有众多假基因或者同源序列。我们知道OCT-4在未分化细胞中高表达,分化细胞中就不表达了,但究竟是否由于OCT-4假基因或者同源序列造成的无人知道。05年遗传发育所的Guangli Suo发现OCT-4在肿瘤里转录,07年Stefanie Liedtke的Cell Stem Cell文章就综合分析了OCT-4序列的冗余性,指出Guangli Suo的纰漏处。这篇文章:Oct4 and Its Pseudogenes Confuse Stem Cell Research.很有代表性,它告诉我们怎样研究基因组中有大量冗余序列的基因。
呵呵,做遗传病的,有时候会连锁或者关联到某个区域,此区域除了假基因别无其他已知基因。那到底是不是假基因造成遗传表型,没人知道。所以就现在研究还不能说假基因能表达或者有功能。
pseudogene的研究主要以processed pseudogene为主,各种争论五花八门,至少到今天为止还没有一篇能站住脚的文献论证假基因是真正有功能的(Toshiaki Watanabe和ERIC.J.DEVOR分别报道过假基因能能包含着microRNA母本,不知道这算不算是有功能)。另外一些学者们推测pseudogene可以稳定其真基因的mRNA甚至可以调控翻译,但都没有明确的证据。
03年,Shinji Hirotsune研究成果在Nature发表,称“假基因可以调控其真基因的mRNA稳定性”,06年Todd A. Gray的PNAS文章提出质疑,他们发现之前的假基因被高度甲基化——既不表达也不稳定其真基因的mRNA。就这个问题,Jeannie T. Lee、Adam Pavlicek、Satoko Kaneko先后撰文做过探讨,但他们都是比较支持假基因有功能的。
04年,Harish V. Pai在JBC撰文发现假基因CYP2D7P1突变能回复功能,并产生编码蛋白。05年JANELLE M. HOSKINS指出他们研究成果可能是由于实验产生的假阳性造成的。
另外,假基因在干细胞领域也比较受关注,因为OCT-4有众多假基因或者同源序列。我们知道OCT-4在未分化细胞中高表达,分化细胞中就不表达了,但究竟是否由于OCT-4假基因或者同源序列造成的无人知道。05年遗传发育所的Guangli Suo发现OCT-4在肿瘤里转录,07年Stefanie Liedtke的Cell Stem Cell文章就综合分析了OCT-4序列的冗余性,指出Guangli Suo的纰漏处。这篇文章:Oct4 and Its Pseudogenes Confuse Stem Cell Research.很有代表性,它告诉我们怎样研究基因组中有大量冗余序列的基因。
呵呵,做遗传病的,有时候会连锁或者关联到某个区域,此区域除了假基因别无其他已知基因。那到底是不是假基因造成遗传表型,没人知道。所以就现在研究还不能说假基因能表达或者有功能。
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