New Genomes Shed Light on Complex Cells

科学家们最近已经测定了另一种酵母的基因组（fission yeast）的基因组，而另两种真菌类的基因组也在测序当中。有趣的是fission yeast 的基因组在现在所有已经测定的真核生物的基因组中是最小的，甚至小于某些低等的原核生物，这就证明了生物的复杂性不是单纯依赖于基因的数目。更有意义的是，这些基因组被拿来进行比较基因组的研究，从而在确定那些基因“构成”了真核生物方面走出了第一步（a first step toward defining the eukaryotic cell）。

Elizabeth Pennisi

COLD SPRING HARBOR, NEW YORK--Biologists have long wondered what genes separate the men from the boys--that is, the complex eukaryotes from the more primitive prokaryotes. Now they are beginning to find out, thanks to new work deciphering the genome sequences of higher organisms.

At a genome sequencing and biology meeting last week,* researchers announced that they have decoded the genetic complement of a second yeast and are in the midst of sequencing two fungi. Already, these three new genome sequences are shedding light on what it takes to be a eukaryotic cell, says Paul Nurse, director of the Imperial Cancer Research Fund in London. By determining which genes these varied organisms have in common and removing those that are also shared by prokaryotes, he and his colleagues have identified the subset of genes that make possible more complex cell functioning.

Yeast, fungi, and all multicellular organisms--from plants to humans--are eukaryotes, with complex cells that have discrete subunits, such as the nucleus and mitochondria, to help with various tasks. For decades, cell biologists have studied yeast, simple, one-celled organisms, for insights into how they and more complex eukaryotes work. Toward that end, in 1996, the yeast research community decoded the genome of the budding yeast, Saccharomyces cerevisiae.

Now a European consortium of 12 labs led by the Sanger Centre in Hinxton, United Kingdom, has sequenced and analyzed the 14-million-base genome of Schizosaccharomyces pombe, also known as fission yeast. The team has even determined three-quarters of the bases in a hard-to-sequence region, called the centromere, that is critical to the proper replication and separation of chromosomes during cell division--a feat few other groups have accomplished on any genome.

Of all the eukaryotes sequenced to date, fission yeast "has the smallest number of genes," with 4944 predicted, Nurse reported at the meeting. Budding yeast has 5805 predicted genes, while humans have some 37,000, by the latest count. Even some lowly bacteria, such as Pseudomonas, have more than 5000 genes. That makes it clear, Nurse says, "that being a eukaryote doesn't simply depend on the number of genes, but the type and context."

Fission yeast is "a stripped-down eukaryote," says Nurse, and as such, it likely contains the bare essentials of the eukaryotic cell, along with genes that define it as a fission yeast. To check this out, Nurse and his colleagues analyzed which genes fission yeast shares with the other sequenced eukaryotes. (These include the budding yeast, human, the plant Arabidopsis, the fruit fly Drosophila melanogaster, and the nematode Caenorhabditis elegans.) With yeast in the six-way comparison, Nurse eliminated genes that in humans and worms, for example, support multicellularity, as well as those genes that help define each species. They then excluded all the genes that fission yeast shares with prokaryotic bacteria or archaea. Those genes that remained are "a first step toward defining the eukaryotic cell," says Nurse.

Eukaryote-only genes include, for example, those that encode proteins involved in the spatial organization of the cell. Other genes produce proteins that help move molecules around and through membranes within a cell. Some code for proteins that organize chromosomes within the nucleus or regulate cell division, while others encode proteins involved in breaking down other proteins. Eric Green, a geneticist at the National Human Genome Research Institute in Bethesda, Maryland, calls the new work an "exciting first pass" that hints at the power of comparing genome sequences to learn not only about what distinguishes eukaryotes from prokaryotes but also about what sets various eukaryotes apart. "It illustrates the exciting analytical glasses that we are going to be able to put on," he adds.

In related work, a team from the Center for Genome Research at the Whitehead Institute in Cambridge, Massachusetts, has taken a first pass at the genome of the fungus Neurospora crassa, another model organism. And the Department of Energy's Joint Genome Institute in Walnut Creek, California, has sequenced and assembled almost 30 million bases of the genome of the fungus Phanerochaete chrysosporium. These fungi have much larger genomes and, presumably, more genes than fission yeast. Comparing these fungal sequences to those of yeast and others will help define the genetic underpinnings of that branch of the eukaryotic family tree.