高等生物中，遗传信息通过卵子、精子（或称配子）从亲代传递到子代。一些单细胞生物体如酵母，基因可以通过孢子（spores）在亲代和子代间传递。在这两种生殖策略中，遗传物质先加倍然后平均分配到配子或者单孢子中。在配子或者单孢子形成的末期，遗传物质（也称染色质）发生剧烈的压缩，体积锐减到原来的5%。
Wistar研究所的研究人员，通过研究酵母单孢子形成过程中控制遗传物质的机制，首次发现一种在染色体压缩过程中发挥关键作用的分子。他们证实：分子“标记”出现于压缩过程之前，并且其出现是压缩过程能够顺利完成的保证。另外，研究人员发现，在果蝇和小鼠的精子形成中，这种分子也发挥相同的活性，提示，控制染色体压缩的机制在进化过程中的保守性。9月15日《Genes & Development》新闻报道了这项新发现，并且在同一期刊上对实验的重大意义做了深入报道。
“这种分子标记在单孢子和精子内部基因组压缩过程中的关键时刻发挥作用，”论文初级作者、Wistar研究所研究员 Shelley L. Berger教授说，“当然在酵母和哺乳动物以外的生命形式中，这种分子标记对于的染色体压缩也可能发挥相似的作用，提示我们：压缩在进化过程中是非常非常重要的一个环节。”
Berger推测，压缩也许能够回答许多重要的生物学假说。
“DNA在配子中是以单链形式存在的，很容易断裂或者发生突变，”她说，“压缩能够保持基因组的稳定性。假如配子中的单链DNA受损，其很有可能断裂，然后以破坏性方式重新组装。”
她强调，双链DNA假如发生损伤，能够以剩下的一条单链为模板依据碱基互补原则重新修复损伤。
“在高等生物中，组装能够影响精子的可孕性和功能，继而影响物种的繁殖能力，”研究小组带头人、Thanuja Krishnamoorthy博士说，“我们有必要更好地了解精子形成过程中基因组装。”
实验中一直强调的分子是一种调节组氨酸的磷分子。组氨酸是一种环绕在DNA周围，与DNA共同组装成核小体的小分子蛋白。成串的核小体是染色体的结构基础。
Krishnamoorthy在酵母实验中检验观察结果。实验过程中，Krishnamoorthy改变了组氨酸上这种关键蛋白附着点。最后发现：这种蛋白不能附着在组氨酸上，压缩过程被严重抑制了。“我们发现实验酵母单孢子内部，染色质的体积明显变大，好像压缩过程消失了一样，”
Berger说，“单孢子形成的成功率也明显下降了。”
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
