Shrinking Bat DNA and Elastic Genomes – Quanta Magazine

Parsing the creatures 2 billion base pairs, Feschotte and his colleagues did stumble on something strange. We found some very weird transposons, he said. Because these oddball parasite sequences didnt appear in other mammals, they were likely to have invaded after bats diverged from other lineages, perhaps picked up from an insect snack some 30 to 40 million years ago. Whats more, they were incredibly active. Probably 20 percent or more of the bats genome is derived from this fairly recent wave of transposons, Feschotte said. It raised a paradox because when we see an explosion of transposon activity, wed predict an increase in size. Instead, the bat genome had shrunk. So we were puzzled.

There was only one likely explanation: Bats must have jettisoned a lot of DNA. When Kapusta joined Feschottes lab in 2011, her first project was to find out how much. By comparing transposons in bats and nine other mammals, she could see which pieces many lineages shared. These, she determined, must have come from a common ancestor. Its really like looking at fossils, she said. Researchers had previously assembled a rough reconstruction of the ancient mammalian genome as it might have existed 100 million years ago. At 2.8 billion base pairs, it was nearly human-size.

Next, Kapusta calculated how much ancestral DNA each lineage had lost and how much new material it had gained. As she and Feschotte suspected, the bat lineages had churned through base pairs, dumping more than 1 billion while accruing only another few hundred million. Yet it was the other mammals that made their jaws drop.

Mammals are not especially diverse when it comes to genome size. In many animal groups, such as insects and amphibians, genomes vary more than a hundredfold. By contrast, the largest genome in mammals (in the red viscacha rat) is only five times as big as the smallest (in the bent-wing bat). Many researchers took this to mean that mammalian genomes just dont have much going on. As Susumu Ohno, the noted geneticist and expert in molecular evolution, put it in 1969: In this respect, evolution of mammals is not very interesting.

But Kapustas data revealed that mammalian genomes are far from monotonous, having reaped and purged vast quantities of DNA. Take the mouse. Its genome is roughly the same size it was 100 million years ago. And yet very little of the original remains. This was a big surprise: In the end, only one-third of the mouse genome is the same, said Kapusta, who is now a research associate in human genetics at the University of Utah and at the USTAR Center for Genetic Discovery. Applying the same analysis to 24 bird species, whose genomes are even less varied than those of mammals, she showed that they too have a lively genetic history.

No one predicted this, said J. Spencer Johnston, a professor of entomology at Texas A&M University. Even those genomes that didnt change size over a huge period of time they didnt just sit there. Somehow they decided what size they wanted to be, and despite mobile elements trying to bloat them, they didnt bloat. So then the next obvious question is: Why the heck not?

Feschottes best guess points at transposons themselves. They provide a very natural mechanism by which gain provides the template to facilitate loss, he said. Heres how: As transposons multiply, they create long strings of nearly identical code. Parts of the genome become like a book that repeats the same few words. If you rip out a page, you might glue it back in the wrong place because everything looks pretty much the same. You might even decide the book reads just fine as is and toss the page in the trash. This happens with DNA too. When its broken and rejoined, as routinely happens when DNA is damaged but also during the recombination of genes in sexual reproduction, large numbers of transposons make it easy for strands to misalign, and that slippage can result in deletions. The whole array can collapse at once, Feschotte said.

This hypothesis hasnt been tested in animals, but there is evidence from other organisms. Its not so different from what were seeing in plants with small genomes, Leitch said. DNA in these species is often dominated by just one or two types of transposons that amplify and then get eliminated. The turnover is very dynamic: in 3 to 5 million years, half of any new repeats will be gone.

Thats not the case for larger genomes. What we see in big plant genomes and also in salamanders and lungfish is a much more heterogeneous set of repeats, none of which are present in [large numbers], Leitch said. She thinks these genomes must have replaced the ability to knock out transposons with a novel and effective way of silencing them. What they do is, they stick labels onto the DNA that signal to it to become very tightly condensed sort of squished so it cant be read easily. That alteration stops the repeats from copying themselves, but it also breaks the mechanism for eliminating them. So over time, Leitch explained, any new repeats get stuck and then slowly diverge through normal mutation to produce a genome full of ancient degenerative repeats.

Meanwhile, other forces may be at play. Large genomes, for instance, can be costly. Theyre energetically expensive, like running a big house, Leitch said. They also take up more space, which requires a bigger nucleus, which requires a bigger cell, which can slow processes like metabolism and growth. Its possible that in some populations, under some conditions, natural selection may constrain genome size. For example, female bow-winged grasshoppers, for mysterious reasons, prefer the songs of males with small genomes. Maize plants growing at higher latitudes likewise self-select for smaller genomes, seemingly so they can generate seed before winter sets in.

Some experts speculate that a similar process is going on in birds and bats, which may need small genomes to maintain the high metabolisms needed for flight. But proof is lacking. Did small genomes really give birds an advantage in taking to the skies? Or had the genomes of birds flightless dinosaur ancestors already begun to contract for some other reason, and did the physiological demands of flight then shrink the genomes of modern birds even more? We cant say whats cause and effect, Suh said.

Its also possible that genome size is largely a result of chance. My feeling is theres one underlying mechanism that drives all this variability, said Mike Lynch, a biologist at Indiana University. And thats random genetic drift. Its a principle of population genetics that drift whereby a genetic variant becomes more or less common just by sheer luck is stronger in small groups, where theres less variation. So when populations decline, such as when new species diverge, the odds increase that lineages will drift toward larger genomes, even if organisms become slightly less fit. As populations grow, selection is more likely to quash this trait, causing genomes to slim.

None of these models, however, fully explain the great diversity of genome forms. The way I think of it, youve got a bunch of different forces on different levels pushing in different directions, Gregory said. Untangling them will require new kinds of experiments, which may soon be within reach. Were just at the cusp of being able to write genomes, said Chris Organ, an evolutionary biologist at Montana State University. Well be able to actually manipulate genome size in the lab and study its effects. Those results may help to disentangle the features of genomes that are purely products of chance from those with functional significance.

Many experts would also like to see more analyses like Kapustas. (Lets do the same thing in insects! Johnston said.) As more genomes come online, researchers can begin to compare larger numbers of lineages. Four to five years from now, every mammal will be sequenced, Lynch said, and well be able to see whats happening on a finer scale. Do genomes undergo rapid expansion followed by prolonged contraction as populations spread, as Lynch suspects? Or do changes happen smoothly, untouched by population dynamics, as Petrovs and Feschottes models predict and recent work in flies supports?

Or perhaps genomes are unpredictable in the same way life is unpredictable with exceptions to every rule. Biological systems are like Rube Goldberg machines, said Jeff Bennetzen, a plant geneticist at the University of Georgia. If something works, it will be done, but it can be done in the most absurd, complicated, multistep way. This creates novelty. It also creates the potential for that novelty to change in a million different ways.

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Shrinking Bat DNA and Elastic Genomes - Quanta Magazine