How would you find out why identical twins differ slightly from one another? You’d turn, of course, to worms. At least that’s what Arjun Raj did. He’s interested in what factors shape our appearance. It’s well-known that as children grow, things like diet and exercise can alter the way they look as adults. But Raj and other molecular biologists suspected something else was going on.
Genetically Identical Worms Are Different – To find that “something else,” ideally you want to rear twins under identical conditions in the lab for about 20 years. Since that’s never going to happen, Raj turned to a tiny worm called C. elegans. Raj, who is now at the University of Pennsylvania, was studying a particular strain of worm that had damage to one of a series of genes that are critical for worms to form digestive systems. Raj grew his worms in the same Petri dishes, with the same food, and yet they didn’t all look the same. “Some fraction of them will look one way,” he says, “and some fraction of them will look a different way, even though they’re really identical.”
Some Genes Switch On, Some Don’t – So what’s going on here? Raj thinks the answer is how genes express themselves. When scientists talk about gene expression, they mean: Is the gene turned on? Is it sending out the instructions for making things the worms need to survive? When a gene expresses itself, it makes a molecule called messenger RNA (mRNA) in various spots in the developing worm. “We have a really nice method of counting individual molecules by fluorescence imaging,” says Raj. “So you can actually see these individual little spots of messenger RNAs within embryos. And by counting those spots, we get a really accurate estimate of how much expression there is.”
Even though the DNA in these worms was all identical, the gene expression was not. Raj was particularly interested in a gene called END-1. Sometimes this gene was on a lot – and sometimes it was hardly on at all.
It’s A Matter Of Chance – “We think this variability is stochastic in nature,” says Raj. “Stochastic” is basically a scientific way of saying “random.” In other words, there was no particular reason that in some worms END-1 was more turned on than in others – it just happened. And in this particular case, the result of this variation is that some worms developed normal guts, and some worms didn’t develop any guts at all. Scott Rifkin, at the University of California, San Diego, was Raj’s co-author on the worm study. He says all this variability makes you wonder how any animal develops normally.
“You have all these things that go wrong, you’ve got all this genetic variation, you have all these fluctuating environments,” says Rifkin, “and yet it works. You don’t see people going out there with third arms growing out of their chest.”
Evolutionary Redundancy – Adrian Streit, a biologist at the Max Planck Institute in Tubingen, Germany, says the reason it works most of the time is that there are multiple genetic pathways to achieve the same thing. “Basically, by having two or three things that do the same,” says Streit. “Even if one of them might not be right 100 percent of the time, if you have two or three that do it, it’s very, very unlikely that all of them fail.” And that built-in redundancy comes to us courtesy of evolution. Rifkin says natural selection weeded out the creatures that didn’t work out a reliable system to make sure arms and legs and kidneys all showed up in the right places.
“The ones that didn’t work, well they didn’t pass on their genes,” says Rifkin. “They didn’t pass on their developmental process to their offspring – they didn’t have any offspring. They didn’t work.” So be glad that the worms you see crawling around got it right. That paved the way for us to develop normally, too. (Arjun Raj)
Caption photo: These mutant nematode worm embryos are genetically identical, but fluorescence imaging shows they are not exactly the same. The pink spots are mRNA molecules involved in gut development. Some twins have spots and some don’t, which means some will develop guts and others won’t.
These nematode worm embryos are genetically identical but do not look exactly the same.
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