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Jurassic Genome
Science, March 9, 2007

 Tyrannosaurus rex, it turns out, had a pretty small genome. A team of American and British scientists estimates that it contained a relatively puny 1.9 billion base pairs of DNA, a little over half the size of our own genome.

The scientists who came up with this estimate--along with estimates for the genomes of 30 other dinosaur species--had no ancient DNA to study. T. rex, after all, became extinct 65 million years ago, and its genome is long gone. Instead, they discovered a revealing correlation: Big genomes tend to be found in animals with big bone cells. By comparing the size of cells in dinosaur fossils to those of living animals, the scientists got statistically sound estimates for the sizes of the dinosaur genomes.

The findings, published by Nature this week, are more than just a curiosity. Chris Organ, a Harvard University paleontologist and the lead author of the new paper, says the estimates shed new light on a big puzzle: Why do the genomes of living species come in such a staggering range of sizes, varying more than 3000-fold in animals? A fruit fly's genome is 350 times smaller than ours, whereas the marbled lungfish genome is 37 times bigger. Recently, some large-scale comparisons of genome sizes have suggested that natural selection may favor big genomes in some species and small genomes in others. But some skeptics argue that genome size may not be adaptive at all. Now, with the advent of what Organ likes to call "dinogenomics," scientists can begin to tease out some answers by adding extinct species to the emerging picture of genome evolution.

The new study will have its most direct impact on tracing the evolution of bird genomes. "Birds are dinosaurs; they're the last vestige," says Organ. Scientists have long noted that birds have small genomes compared to reptiles, their closest living relatives, but it was unclear how and when that change occurred. Organ's study suggests that the dinosaur ancestors of birds had evolved small genomes long before birds took to the sky. "I think it's very exciting," says T. Ryan Gregory, an expert on genome size at the University of Guelph in Canada. "It's the kind of paper we've needed for a long time."

Giant genomes in lowly creatures

The wide array of genome sizes startled scientists when it came to light in the early 1950s. Until then, the prevailing wisdom had been that complex animals needed bigger genomes than simple ones needed. And yet, as one paper explained, a salamander's genome "contains 70 times as much DNA as is found in a cell of the domestic fowl, a far more highly developed animal." As researchers sized up more genomes, the paradox grew deeper. Some single-celled protozoans turned out to have bigger genomes than humans. The genome of Gonyaulax polyhedra, for example, is 28 times the size of ours.

A solution of sorts emerged in the 1970s: so-called junk DNA. In addition to protein-coding genes, genomes contain stretches of DNA that encode RNA molecules or are just vestiges of old genes. Many genomes, including our own, are dominated by viruslike sequences of DNA called mobile elements that can make new copies of themselves that get inserted in new spots in the same genome. The human genome is 98.5% noncoding DNA.

Comparing the genomes of living species, scientists have found that genomes can expand and shrink quickly, with mobile elements spreading like a genomic plague. The cotton genome, for example, tripled in size over the past 5 million to 10 million years. On the other hand, copying errors can cause cells to snip out large chunks of noncoding DNA by accident, shrinking their genomes in the process.

To test whether natural selection plays a strong role in determining the size of a species' genome, scientists have compared a wide range of species, searching for correlations between genome size and other traits that might be adaptive. Finding these correlations has been difficult, however, because relatively few genomes had been measured until recently, and many of those measurements turned out to be wrong. Genome sizes are easy to misjudge, even with modern genome sequencing methods. When scientists sequence a genome, they generally break it up into fragments and then try to piece them together like a puzzle. Noncoding DNA is loaded with repeating sequences, which are difficult to reassemble properly.

Things are improving, says Gregory. New techniques are enabling more-precise measurements--for instance, scientists are adding DNA-staining compounds to cells and then using image-processing software to analyze the amount of stain. And the results of these studies are now being stored in online databases, making possible large-scale comparisons. Gregory maintains a database of animal genome sizes at the University of Guelph (, Kew Gardens biologists manage one for plants and algae (, and biologists at the Estonian University of Life Sciences run a database for fungi ( Together, the databases contain information on more than 10,000 species.

One of the first correlations scientists noticed was between the size of genomes and the size of cells. It cropped up in a study on red blood cells in vertebrates. Later studies also found a link between cell size and genome size in other groups of species, such as plants and protozoans, and in other types of cells in vertebrates, although not all.

Some scientists have argued that natural selection favors big or small genomes because they produce big or small cells. Take the case of Trichomonas vaginalis, a sexually transmitted protozoan that lives in the human vagina. When a multi-institute group led by Jane Carlton, who is now at New York University, published the organism's genome in the 12 January issue of Science (p. 207), they observed that T. vaginalis is padded with far more mobile elements than are found in related protozoans that live elsewhere in the body. The scientists suggest that when T. vaginalis moved into its current ecological niche, its genome expanded rapidly. The protozoan itself became bigger as a result, which made it more effective at chasing and engulfing its bacterial prey.

Changing cell size may benefit other kinds of species in other ways. In some groups of animals, species with high metabolic rates tend to have small genomes, for example, whereas species with slow metabolisms have big ones. One possible explanation is that small genomes give rise to small blood cells, which have a high surface-to-volume ratio and can transport oxygen faster across their membranes. If a warm-blooded animal needs to use a lot of oxygen to fuel its metabolism, a small genome might give it an evolutionary edge.

The fossil record

Consistent with this hypothesis, birds have much smaller genomes than those of their reptilian relatives. But if birds evolved smaller genomes for their high metabolism, the question naturally arises, when did that shrinkage take place? Organ realized that dinosaur fossils might hold the answer.

Some dinosaur fossils are so well preserved that they still have the cavities that once held their bone cells (known as osteocytes). But no one had ever established a link between genome size and osteocyte size. "That was our first step," says Organ. They examined bones from 26 species of birds, reptiles, mammals, and amphibians. With colleagues at Harvard and the University of Reading, U.K., he mapped his measurements onto an evolutionary tree. The correlation was good enough that they could use the size of a species' osteocytes to accurately predict its genome size. The scientists then added to the tree branches for 31 species of dinosaurs and used the size of their osteocytes to estimate the size of their genomes. From that information, they inferred how the size of dinosaur genomes had evolved over time.

Their analysis suggests that the common ancestor of dinosaurs, a small four-footed reptile that lived about 230 million years ago, had a relatively big genome about the same size as an alligator's. That common ancestor gave rise to several major branches of dinosaurs. One of those branches, the ornithischians, included big herbivores such as stegosaurs and Triceratops. Their genomes did not change much. "These guys have a typical reptilian-sized genome," says Organ.

But another branch of dinosaurs--bipedal predators known as theropods--evolved significantly smaller genomes. Theropods would ultimately give rise to birds. "This blows out of the water the idea that small genomes coevolved with flight," says Organ.

Organ suggests that theropods evolved to have higher metabolic rates than other dinosaurs had, and as a result, natural selection favored smaller genomes and smaller cells. Other paleontologists have also found evidence for bird biology in bipedal dinosaurs, including feathers, rapid growth, and nesting behavior. "You don't decide you're going to fly and be warm-blooded like a bird and then make all these changes," says Organ. "They're all small cumulative things that go way, way back, and they come together to produce this end form."

Although Gregory and others praise Organ's paper, some scientists are not as impressed. "It's a cute paper, but I'm not terribly confident in the outcome," says Michael Lynch of Indiana University, Bloomington, who questions whether natural selection is responsible for driving genomes to different sizes to fine-tune metabolism. "There's a correlation of the two, but I don't know of any direct demonstration of causality."

Gregory concedes that even if metabolism can account for the small genomes of animals such as dinosaurs and birds, it won't explain all the patterns scientists find. Plants, for example, have a similar correlation between cell size and genome size, for example, but they don't have an animal-like metabolism. It's possible that plants have different genome sizes because genome size changes the way their cells capture sunlight or transport fluids. "Any one feature isn't really going to cover it," Gregory says. "You have to look from the bottom up and the top down in every case."

Copyright 2007 Carl Zimmer

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