高等生物中,，遺傳信息通過卵子,、精子（或稱配子）從親代傳遞到子代。一些單細(xì)胞生物體如酵母,，基因可以通過孢子（spores）在親代和子代間傳遞,。在這兩種生殖策略中,，遺傳物質(zhì)先加倍然后平均分配到配子或者單孢子中。在配子或者單孢子形成的末期,，遺傳物質(zhì)（也稱染色質(zhì)）發(fā)生劇烈的壓縮,，體積銳減到原來的5%。
Wistar研究所的研究人員,，通過研究酵母單孢子形成過程中控制遺傳物質(zhì)的機(jī)制,，首次發(fā)現(xiàn)一種在染色體壓縮過程中發(fā)揮關(guān)鍵作用的分子。他們證實(shí)：分子“標(biāo)記”出現(xiàn)于壓縮過程之前,，并且其出現(xiàn)是壓縮過程能夠順利完成的保證,。另外，研究人員發(fā)現(xiàn),，在果蠅和小鼠的精子形成中,，這種分子也發(fā)揮相同的活性，提示,，控制染色體壓縮的機(jī)制在進(jìn)化過程中的保守性,。9月15日《Genes & Development》新聞報(bào)道了這項(xiàng)新發(fā)現(xiàn)，并且在同一期刊上對(duì)實(shí)驗(yàn)的重大意義做了深入報(bào)道,。
“這種分子標(biāo)記在單孢子和精子內(nèi)部基因組壓縮過程中的關(guān)鍵時(shí)刻發(fā)揮作用,，”論文初級(jí)作者、Wistar研究所研究員 Shelley L. Berger教授說,，“當(dāng)然在酵母和哺乳動(dòng)物以外的生命形式中,，這種分子標(biāo)記對(duì)于的染色體壓縮也可能發(fā)揮相似的作用，提示我們：壓縮在進(jìn)化過程中是非常非常重要的一個(gè)環(huán)節(jié),。”
Berger推測(cè),，壓縮也許能夠回答許多重要的生物學(xué)假說。
“DNA在配子中是以單鏈形式存在的,，很容易斷裂或者發(fā)生突變,，”她說，“壓縮能夠保持基因組的穩(wěn)定性,。假如配子中的單鏈DNA受損,，其很有可能斷裂，然后以破壞性方式重新組裝,。”
她強(qiáng)調(diào),，雙鏈DNA假如發(fā)生損傷，能夠以剩下的一條單鏈為模板依據(jù)堿基互補(bǔ)原則重新修復(fù)損傷,。
“在高等生物中,，組裝能夠影響精子的可孕性和功能，繼而影響物種的繁殖能力,，”研究小組帶頭人,、Thanuja Krishnamoorthy博士說,，“我們有必要更好地了解精子形成過程中基因組裝。”
實(shí)驗(yàn)中一直強(qiáng)調(diào)的分子是一種調(diào)節(jié)組氨酸的磷分子,。組氨酸是一種環(huán)繞在DNA周圍,，與DNA共同組裝成核小體的小分子蛋白。成串的核小體是染色體的結(jié)構(gòu)基礎(chǔ),。
Krishnamoorthy在酵母實(shí)驗(yàn)中檢驗(yàn)觀察結(jié)果,。實(shí)驗(yàn)過程中，Krishnamoorthy改變了組氨酸上這種關(guān)鍵蛋白附著點(diǎn),。最后發(fā)現(xiàn)：這種蛋白不能附著在組氨酸上,，壓縮過程被嚴(yán)重抑制了。“我們發(fā)現(xiàn)實(shí)驗(yàn)酵母單孢子內(nèi)部,，染色質(zhì)的體積明顯變大,，好像壓縮過程消失了一樣，”
Berger說,，“單孢子形成的成功率也明顯下降了。”
In higher order animals, genetic information is passed from parents to offspring via sperm or eggs, also known as gametes. In some single-celled organisms, such as yeast, the genes can be passed to the next generation in spores. In both reproductive strategies, major physical changes occur in the genetic material after it has been duplicated and then halved on the way to the production of mature gametes or spores. Near the end of the process, the material – called chromatin, the substructure of chromosomes – becomes dramatically compacted, reduced in volume to as little as five percent of its original volume.
Researchers at The Wistar Institute, studying the mechanisms that control how the genetic material is managed during gamete production, have now identified a single molecule whose presence is required for genome compaction. Their experiments showed that the molecule "marks" the chromatin just prior to compaction and that its presence is mandatory for successful compaction. Additionally, after first noting the molecule's activity during the production of yeast spores, the scientists saw the same activity during the creation of sperm in fruit flies and mice, suggesting that the mechanisms governing genome compaction are evolutionarily ancient, highly conserved in species whose lineages diverged long ago. A report on the new study appears in the September 15 issue of Genes & Development. A "Perspectives" review in the same issue expands on the significance of the findings.
"This molecular mark is required at a critical time leading up to genome compaction in spores and sperm," says Shelley L. Berger, Ph.D., the Hilary Koprowski Professor at The Wistar Institute and senior author on the study. "Also, there seems to be a similarity in the way the mark is used in organisms as different from each other as yeast and mammals, suggesting that compaction has been important throughout evolution."
Berger speculates that compaction might answer a number of important biological purposes.
"During the time the DNA is single-stranded, as it is in the gametes, it's much more susceptible to breaks and mutations," she says. "Compaction may keep the genome resistant to damage of all kinds. This is critical – if the single-stranded DNA in gametes breaks, it can fall apart and possibly reassemble itself in devastating translocations."
She notes that normal double-stranded DNA, on the other hand, has the ability to repair breaks in one of its single strands by using the chemical bases in the companion strand as a reference. Bases in DNA pair only in predetermined combinations, so that one strand can serve as a template for the other.
"Compaction might also affect sperm fertility and function in the higher organisms, and thus the propagation of the species," says Thanuja Krishnamoorthy, Ph.D., lead author on the study. "It's vital that we better understand genome compaction during the production of mature sperm."
The molecule in question is a phosphorous molecule that modifies a histone. Histones are relatively small proteins around which DNA is coiled to create structures called nucleosomes. Compact strings of nucleosomes, then, form into chromatin, the substructure of chromosomes.
To test the team's observations, Krishnamoorthy performed an experiment in yeast in which she altered the histone's chemical composition at a single point, the point at which the molecule attaches to, or marks, the histone. The results were clear and compelling: With the alteration, the molecule was unable to attach to the histone, and compaction was severely limited.
"We saw a significant increase in genomic volume in the resulting yeast spores, as though the compaction had been lost," Berger says. "The frequency of successful spore creation was also lowered significantly."
Franklin Hoke | Source: EurekAlert!
Further information: www.wistar.org
