2012顶尖基因组研究盘点

2012顶尖基因组研究盘点

Top Genomes of 2012

What researchers learned as they dug through some of the most interesting genomes sequenced this year

By Beth Marie Mole | December 20, 2012

基因组研究是一门新兴的、发展迅速的生命科学，其普遍应用及向其他学科、领域的不断渗透日趋明显，这些学科涵盖了现代农业、生物能源、生态环境和人类健康等各个方面。随着测序成本的下降，基因组研究成果也呈现井喷之势。近日The Scientist对2012年最突出的基因组研究进行了盘点……

1.Tomato, tomäto

Species: Tomato, Solanum lycopersicum

Genome size: 900 million base pairs

After a 9-year effort by researchers in 14 countries, the first genome sequence of a tomato—of the original Heinz ketchup variety—was released this May. Anticipation of the fleshy fruit’s genome stems from what the sequences could tell researchers about the tomato’s economically important relatives, including potato, eggplant, tobacco, and pepper. The potato, for instance, which has also recently had its genome sequenced, is 92 percent genetically similar to the tomato. Now, scientists can start figuring out how the differing 8 percent of their genes make tomato plants producing luscious, above ground fruit, while potato plants result in knobby, subterranean tubers. The tomato genome sequence also revealed that the species has triplicated its genome—twice. A triplication event happened around 130 million years ago, then again about 60 million years ago, right around the time that many dinosaur species went extinct. The copy error could have helped tomato plants survive the transitional era.

The Tomato Genome Consortium, “The tomato genome sequence provides insights into fleshy fruit evolution,” Nature, doi:10.1038/nature11119, 2012. (Cited 17 times)

西红柿

西红柿又名番茄、洋柿子、狼桃、番李子、金橘……这种最初被视为有毒物的蔬菜，至今已经在我们日常饭桌上十分常见了，但是对于这种植物的遗传机制，科学家们了解的还并不是很多。来自美国康奈尔大学，英国诺丁汉大学，中科院国家基因研究中心等处的研究人员首次公布了西红柿（Solanum lycopersicum）的基因组，此次测序的西红柿品种为Heinz 1706。

这项研究报道称，西红柿共有约35000个基因，12条染色体，研究人员捕获了关于西红柿的各种特性，包括味道，天然抗虫性，以及营养成分等、实质上的几乎所有基因。

文章详细描述了这些基因的序列，以及其在染色体上的分布，西红柿基因组序列分析有助于肉质果实的进化研究，这些信息也将能用于培育人们喜欢的改良后的口味和更加丰富的营养，如番茄红素，除此之外，在降低成本，对抗病原体，干旱和瘟疫等方面，基因组序列也提供了重要信息。

这项序列分析还揭示了西红柿基因的相对关联，这将有助于揭示西红柿基因和其展现的特性之间的关系。西红柿作为茄科家族的成员之一，其新序列也将为确认西红柿茄科亲属，比如土豆，辣椒，茄子和矮牵牛等，提供参考。目前从经济价值和产量来看，茄科家族是世界最重要的蔬菜作物家族。

2.Incubating offspring

Species: Human fetus, homo sapiens

Genome size: 3 billion base pairs

Following up on a 1997 Lancet study that found fetal DNA circulating in maternal blood, this year saw a steady stream of studies and clinical trials on sequencing fetal DNA, including a whole fetal genome, published in June. The new technology relies on the fact that DNA from the baby makes up 3 to 10 percent of the cell-free DNA floating through a pregnant woman’s blood stream. As expected, the new technology has exploded onto the market as non-invasive screens for genetic disorders in fetuses as early as 9 weeks into pregnancy. Currently, the three tests on the marker focus on finding aneuploidies—abnormalities in the number of chromosomes or chromosomal regions, including trisomy 21, the cause of Down syndrome. But, the continued advancement of sequencing technologies promises more extensive tests in the near future. For more on prenatal genetic tests, the state of the industry, and the associated ethical issues, check out The Scientist’s article, “Year of the Fetus.”

J.O. Kitzman et. al., “Noninvasive whole-genome sequencing of a human fetus,” Science Translational Medicine, 137: 137ra76, 2012. (Cited 10 times)

胎儿

来自美国华盛顿大学，意大利巴里大学等多处研究机构组成的研究小组成功完成了非侵入性胎儿全基因组重构测序，这种方法为胎儿非侵入性评估所有单基因遗传疾病，开启了一道门。这项工作证明了通过单次非侵入性检测，扫描胎儿全基因组，分析超过3000种单基因疾病的可能性。

最新这项研究的方法区别于其它研究之处，在于能分析胎儿基因组中更多，更微小的变化，小到DNA编码中一个碱基的而变化。利用统计学建模方面的技术进步，这一研究团队克服了一些研究难题，比如血浆样品中胎儿DNA所占比例小，如何能分析找到从母体传递给胎儿的遗传变异呢？另外，存在两种类型的基因变异：遗传性突变及全新的基因突变，母体基因组中含有数百万个遗传变异，它们基因组中进行了重组，这些突变如何区分呢？

研究人员采用了一种新型单倍体分析方法，从中他们能找到胎儿来自父亲和母亲的遗传物质，准确度超过98%，并且研究人员还能分析单倍体型在每个染色体上是如何组成的，新的变异可通过对来自母血中的血浆DNA的信息进行计算分析而发现。不过研究人员也表示，这项技术还需要更进一步的完善，他们认为有必要建立更全面，可扩展的总体指导手册，用以降低成本，提高检测过程的自动化程度，以及标准度。

3.Gorilla, exposed

Species: Western lowland gorilla, Gorilla gorilla gorilla

Genome size: 3.04 billion base pairs

In March, a 30-year-old, 300-pound captive gorilla named Kamilah revealed new similarities between us and our second-closest relatives. By analyzing Kamilah’s fully sequenced genome—all 21,000 genes of it—researchers at the Sanger Institute in Cambridge, United Kingdom, found that gorillas split from humans and chimps around 10 million years ago—3 million years before humans diverged from chimps. Thus it’s not surprising that most human and chimp genes are more genetically similar to each other than to gorilla genes, but researchers found that 30 percent of gorilla genes are also closely related to human and chimp genes—sometimes more similar than those genes are between human and chimps. Such shared genetics suggests that the three species continued to interbreed after their evolutionary divorce. “As the climate changed, populations fragmented, evolved separately, and the small splinter groups either died out or found creative ways to carry on, such as breeding with other groups,” lead author Aylwyn Scally of the Sanger Institute told New Scientist. Kamilah’s genome also showed that 500 of the genes shared between apes and humans—mostly involved in hearing and brain development—evolved in gorillas after the two species split.

A. Scally et. al., “Insights into hominid evolution from the gorilla genome sequence,” Nature, 483: 169-75, 2012. (Cited 13 times)

大猩猩

来自英国Wellcome Trust基因科学园的研究人员完成了大猩猩的基因组测序，标志着当前存活的猿科动物最后一个属的基因组也得以破解。

科学家们第一次将所有存活的四种猿科动物包括人类、黑猩猩、大猩猩和红毛猩猩（orang-utans）的基因组进行比对。对人类、黑猩猩和大猩猩中超过11,000个基因进行了筛查，以寻找对进化具有重要意义的遗传改变。

研究小组发现尽管就基因组大部分序列而言，人类和黑猩猩在遗传关系上最接近，但也有许多序列并非如此。有15%的人类基因组序列更接近大猩猩基因组序列而非黑猩猩，有15%的黑猩猩序列更接近大猩猩序列而非人类。研究人员还发现三种猿科动物与感官知觉、听觉和大脑发育相关的基因均显示了加速进化，尤其是人类和大猩猩。该研究小组发现大猩猩从人类和黑猩猩中分支出去是在大约1000万年前。东部和西部大猩猩现在也存在遗传差异，但它们分离则近得多，大概在100万前左右，且分离是逐步的。

该研究以独特的视角了解了人类的起源，并为研究人类进化和生物学，以及大猩猩生物学和保护提供了重要的资源。

4. All-purpose pork

Species: Domestic pig, Sus scrofa domesticus

Genome size: ~3 billion base pairs

After decades of genetic work, and 10,000 years of a human-pig relationship, researchers last month (November) sequenced the full genome of a domesticated pig—a female fromIllinoisnamed T.J. Tabasco. The most immediate applications of this new genetic information will most likely be seen on the farm, where breeders will try to elbow out genes that are linked to disease susceptibility, such as the porcine reproductive and respiratory syndrome that costs the pig industry $600 million each year. But, in addition to the promise of healthier, meatier animals for food production, the new genomic data could be used for medical advances: researchers have been working for years to use pigs as models for human disease and have even envisioned using them to grow human organs for transplantation. Exploiting similarities in anatomy, pigs are already models for human eye diseases, cystic fibrosis, and diabetes. Now, researchers are working to develop pig models of Alzheimer’s disease, cancer, and muscular dystrophy.

M.A.M. Groenen et al., “Analysis of pig genomes provide insight into porcine demography and evolution,”Nature, 491: 393-98, 2012 (Cited 3 times)

猪

由伊利诺大学、荷兰瓦格宁根大学和爱丁堡大学的研究人员领导的国际猪基因组测序联盟完成了对家猪和野猪的最为全面的一次基因组分析。

研究人员将一种常见农场猪Susscrofa domesticus与10种野猪的基因组进行了比较。所有这些动物来自欧洲和亚洲的不同地区。他们还将猪的基因组与人类、小鼠、狗、马和牛的基因组进行了比较。

研究小组发现了成为家猪祖先后Sus scrofa进化的一些新细节，其与现在的野猪非常的相似，首先出现于南亚，后逐渐迁移跨越亚欧大陆。比较亚洲和欧洲野猪揭示出显著的遗传差异，结果表明它们彼此分离大约是在100万年前。

研究人员报告说在家猪中一些基因家族经历了相对快速的进化，有一些免疫基因和嗅觉基因迅速扩增。尽管猪能够闻到人类和许多其他动物无法闻到的许多东西，但它们的味觉在一定程度上受到损害。猪能够高度耐受包含大量盐的食物，或是人类味觉排斥的东西。相比人类，猪的苦味受体基因显著减少，此外猪和人类感知甜味和鲜味的基因也有不同。

总体上，研究人员发现了112个位点上的猪蛋白具有与人类疾病相关的相同氨基酸。证实猪与人类共同拥有一些与肥胖、糖尿病、阅读障碍（dyslexia）、帕金森氏病和阿尔茨海默氏症相关的蛋白质变异。

研究人员表示这一工作对于农业具有重要的意义，推动我们了解了进化，将有助于人类医学。

5.Spirited grains

Species: Barley, Hordeum vulgare L.

Genome size: ~5.3 billion base pairs

Barley is the world’s fourth most important cereal crop, and one of the first domesticated grains, but more importantly, it’s critical for the production of beer and whiskey. So, the study released this past October revealing the whole genome sequence—twice the size of the human genome—met cheers from agricultural producers, distillers, and brew masters alike. The genome draft—produced by the International Barley Genome Sequencing Consortium, a team of researchers at 22 organizations around the world—is a high-resolution map of the grain’s haploid genome, including most of its 32,000 genes. Agricultural researchers hail the new data as a way to make the staple grain more resistant to disease and resilient during climate change, thereby fortifying food security. But, beer and whiskey drinkers are looking to use the new data to brew better spirits.

K. Mayer et al., “A physical, genetic and functional sequence assembly of the barley genome,” Nature, 491: 711-16, 2012. (Not yet cited)

大麦

大麦是世界上最重要的粮食作物之一，近日Nature公布了目前为止最完善的大麦基因组测序图谱[1]。将成为人们提高大麦产量、增强大麦抗虫抗病能力、增加大麦营养价值的有力工具。

大麦的基因组几乎是人类或玉米基因组的两倍大，这对于测序来说是个挑战。大麦基因组的复杂性和大量重复区域更增添了基因组有序装配的难度。研究人员开发并应用了一系列创新策略，终于克服了这些困难，利用Illumina和Roche 454测序平台得到了高分辨率的基因组装配图谱。该图谱几乎包括了大麦的所有基因和相关调控区域，为那些希望通过功能基因组学和育种对大麦进行改良的研究者们提供了新的研究方向。

研究人员构建了4.98 Gb的大麦基因组物理图谱，包括3.90 Gb高分辨率遗传图谱，并用基因组鸟枪法装配和深度RNA测序等数据进行补充。研究确定了79,379个转录本，包括26,159个可信度高的基因。研究人员指出，大麦基因组中丰富的选择性剪切、提前终止密码子和新转录活性区域显示转录后剪切是重要的调控层面。

此外，研究人员详细解析了大麦基因组功能区域，揭示了几乎所有32000个基因的排列和结构，并标注了在不同组织不同发育阶段这些基因启动的时间和地点。研究人员重点描述了大麦基因组的动态区域，就是这些区域的基因赋予大麦抵御重大疾病的抗性，例如白粉病、赤霉病和锈病。文章还提供了迄今为止最详尽的大麦品种间遗传差异。