假基因

假基因（Pseudogenes，Pseudo-意为“假”）是一类染色体上的基因片段。假基因的序列通常与对应的基因相似，但至少是丧失了一部分功能，如基因不能表达或编码的蛋白质没有功能。
一般认为，假基因最初是功能对生物生存并非必要的基因。随着突变的积累，出现编码区提前出现终止密码子、移码突变等情况，逐渐变为无功能的假基因。另外，拷贝数变异（Copy-number variation, CNV）也可能产生假基因。在拷贝数变异中，1kb（千碱基对）以上的DNA片段会发生复制或删除。一部分假基因既没有内含子，也没有启动子（这种启动子被认为是通过mRNA的逆转录转移到染色体上的，称为“加工”假基因（processed pseudogenes）），但部分假基因仍然拥有一些与正常基因相同的特征，比如拥有CpG岛等启动子、RNA剪接位点等。
假基因这一名词是由雅克（Jacq）等人于1977年最早提出的。长期以来生物学家们认为假基因是没有功能的垃圾DNA，惟近年来的研究还表明假基因和其他非编码片段一样，拥有调控基因表达的功能。假基因的调控作用对维持生物体的生理活动有着重要意义，一部分假基因在某些疾病的发展中也扮演着重要角色。
在进化生物学研究中，这些因为演化而丧失功能的假基因，对他们进行序列分析意义则相对重大，一直是研究者获知生物进化历程的手段。假基因一般会拥有一些源基因的特征。按照进化论的观点，两个亲缘关系较近的物种拥有同一祖先。对假基因进行序列比对、分析，即可验证两物种是否拥有同一祖先，并能计算出两物种开始分离的时间（结果能精确到百万年）。

类型及成因

根据不同的起源机制和特点，假基因可大致分为如下四类：

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Processed

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 or hnRNA 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 an RNA 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, these insertions occasionally contribute exons to existing genes, 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. Processed pseudogenes are continually being created in primates. Human populations, for example, have distinct sets of processed pseudogenes across its individuals.

Non-processed

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 caused by homologous recombination at, for example, repetitive sine sequences on misaligned chromosomes and subsequently acquire mutations that cause the copy to lose the original gene's function. Duplicated pseudogenes usually have all the same characteristics as genes, including an intact exon-intron structure and regulatory 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. If pseudogenization is due to gene duplication, it usually occurs in the first few million years after the gene duplication, provided the gene has not been subjected to any selection pressure. Gene duplication generates functional redundancy and it is not normally advantageous to carry two identical genes. Mutations that disrupt either the structure or the function of either of the two genes are not deleterious and will not be removed through the selection process. As a result, the gene that has been mutated gradually becomes a pseudogene and will be either unexpressed or functionless. This kind of evolutionary fate is shown by population genetic modeling and also by genome analysis. According to evolutionary context, these pseudogenes will either be deleted or become so distinct from the parental genes so that they will no longer be identifiable. Relatively young pseudogenes can be recognized due to their sequence similarity.

Unitary pseudogenes

Various mutations (such as indels and nonsense mutations) can prevent a gene from being normally transcribed or translated, and thus the gene may become less- or non-functional or "deactivated". These are the same mechanisms by which non-processed genes become pseudogenes, but the difference in this case is that the gene was not duplicated before pseudogenization. Normally, such a pseudogene 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. Another more recent example of a disabled gene links the deactivation of the caspase 12 gene (through a nonsense mutation) to positive selection in humans.
It has been shown that processed pseudogenes accumulate mutations faster than non-processed pseudogenes.

Pseudo-pseudogenes

The rapid proliferation of DNA sequencing technologies has led to the identification of many apparent pseudogenes using gene prediction techniques. Pseudogenes are often identified by the appearance of a premature stop codon in a predicted mRNA sequence, which would, in theory, prevent synthesis (translation) of the normal protein product of the original gene. There have been some reports of translational readthrough of such premature stop codons in mammals, as reviewed in the "Translational readthrough" section of the stop codon article. As alluded to in the figure above, a small amount of the protein product of such readthrough may still be recognizable and function at some level. If so, the pseudogene can be subject to natural selection. That appears to have happened during the evolution of Drosophila species, as described next.
In 2016 it was reported that 4 predicted pseudogenes in multiple Drosophila species actually encode proteins with biologically important functions, "suggesting that such 'pseudo-pseudogenes' could represent a widespread phenomenon". For example, the functional protein (an olfactory receptor) is found only in neurons. This finding of tissue-specific biologically-functional genes that could have been dismissed as pseudogenes by in silico analysis complicates the analysis of sequence data. As of 2012, it appeared that there are approximately 12,000–14,000 pseudogenes in the human genome, almost comparable to the oft-cited approximate value of 20,000 genes in our genome. The current work may also help to explain why we are able to live with 20 to 100 putative homozygous loss of function mutations in our genomes.
Through reanalysis of over 50 million peptides generated from the human proteome and separated by mass spectrometry, it now (2016) appears that there are at least 19,262 human proteins produced from 16,271 genes or clusters of genes. From this analysis, 8 new protein coding genes that were previously considered pseudogenes were identified.

细菌假基因

细菌基因组中也存在假基因。这些拥有假基因的细菌通常为共生或细胞内寄生，因此它们不需要一些生活在外界复杂环境中的细菌所必须的基因。一个极端的例子是麻风病的病原体--麻风杆菌（Mycobacterium leprae）的基因组，已报道有1,133个假基因约占其转录组的50%。