Some Assembly Required Computational biologist Steven Salzberg spoke with GeneWatch about the future of genome sequencing.
Steven Salzberg, PhD, is a Professor of Medicine in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University. Genome sequencing in 20 years: Certainly things are very different than they were 20 years ago. Most of the changes have been incremental, but adding things up, it’s been quite dramatic. Extrapolating forward, I don’t know if there will be any revolutionary changes; but even with steady progress, 20 years is a long time, and things will look very different from the way they look now. One thing that we need to solve, and something I’ve worked on, is the assembly of genomes. I’d like to think that in less than 20 years we’ll have either solved it, or there will be such dramatic progress that it won’t be a problem anymore. We have sequenced thousands of species. Almost all of them, with the exception of some bacteria, are draft genomes. That means there are gaps in the sequence, and there are parts of the sequence that aren’t really positioned correctly, they’re not lined up along chromosomes; so we can stitch them together, but we don’t know what the chromosome structure is. That’s true of nearly every genome out there, and in fact there are still gaps in the human genome. The advent of next-generation sequencing has dramatically sped 24 GeneWatch
up the rate at which we’re tackling new species, but they remain draft genomes; in fact, the quality of draft genomes has probably gone down a little bit with next generation sequencing. How we sequence the genome today (and tomorrow): We break it into a very large number of pieces, and we sequence those pieces in very short reads of 100 base pairs or so. Then we use a program, like the programs my group develops, to put it all together. That process has various laboratory steps and very complicated computational steps that are imperfect, so you don’t get the whole genome reconstructed at the end. A better way to do it would be to just grab a chromosome and read it from one end to the other. You wouldn’t have to assemble it; you’d just have the chromosome sequence at the end. And there are people who are working on ways to read longer and longer stretches of DNA—without any big breakthroughs lately, but somehow we’ve got to get there, and hopefully within the next 20 years we will. If we come up with better technology to help us sequence the genome, hopefully we’ll be able to sequence more genomes even faster—and they’ll be complete instead of drafts.
genome are the genes, so we’re constantly discovering new functional parts of genomes that are either genes or regulatory sequences that control genes; but it’s very piecemeal. In a way, that makes it more exciting, because you never know what you’re going to find—even looking at well studied genomes you can find lots of new things—but I’m hoping we’ll develop new and better methods for figuring out which parts of the genome are important to the organism. For humans, I would like to be able to see a full catalog of all the genes. We don’t have a catalog of all the human genes yet. In fact, we don’t even know the precise number of human genes. So sometime, maybe in the next 20 years, we’ll actually be able to say that we have the complete list of human genes—that is, all the protein coding genes and all the RNA genes.
Discovering new genes: We use a lot of indirect methods to try to figure out which parts of the January-February 2012