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Faster and faster, but not better and better – yet
and destroy RNA copies of genes with a complementary sequence, preventing protein production. MicroRNAs work in a similar way but are not as specific, controlling the activity of many genes simultaneously. Piwi-acting RNAs, meanwhile, shut down the parasitic genes that litter our genome to stop them wreaking havoc, though it’s not clear how.
Nonintelligent design The list of regulatory RNAs grows longer by the day. In some cases, though, it is the act of making RNA rather than the product that matters: producing an RNA copy of one DNA strand chemically alters the proteins around which DNA is wrapped, shutting down genes on the opposite strand. Such convoluted mechanisms might seem odd and rather wasteful, but that is just what we should expect. “You sometimes ask yourself, ‘Why on earth is biology working this way?’,” says Birney. “But from evolution’s perspective it doesn’t have to look good in a textbook, it just has to work.” Unfortunately, it only has to work in some of us. The Byzantine complexity and nonintelligent design of our genomes means there is an awful lot that can go wrong, and all too often it does, argues John Avise of the University of California, Irvine. Splicing mistakes and errant microRNAs play a role in some cancers, for instance. On the bright side, discoveries like siRNA could lead to potent new treatments for all kinds of diseases. What’s certain is that there is much more to discover. “The genome is the start, not the end of the process,” says Birney. Michael Le Page
Evolution’s secrets You may be part Neanderthal – one of the many revelations about us emerging from genome sequencing. “It is revolutionising the way that we think about the evolution of humans,” says anthropologist John Hawks of the University of Wisconsin-Madison. Genomes provide a huge amount of information compared with fossils alone. The DNA in every organism is the latest link in an unbroken chain stretching back more than 3 billion years to the very dawn of life, changing a little with each generation. So by comparing the genomes of different people and animals – sometimes long-dead ones – it’s possible to work out what changed, and even when and where. Genome studies suggest, for instance, that some modern humans interbred not only with Neanderthals but also with other Homo species after they left Africa. And far from slowing down recently, human evolution began accelerating around 40,000 years ago
and has been speeding up ever since, Hawks has shown. The reason? A bigger population produces more potentially beneficial mutations, while the rise of farming and city living are exerting novel selective pressures. For example, gene variants that allow some adults to digest milk first appeared 7000 years ago, around the time that cattle were domesticated. It is possible to trace not just variants but also when and how genes first evolved. For example, the syncytin gene, which plays a crucial role in pregnancy, was originally acquired from a virus – one of many examples of gene transfer between different species. At the moment, we don’t understand the significance of the vast majority of the differences between genomes. Over the coming decades, however, we will be able to pinpoint the precise mutations that turned our tree-living ancestor into a naked, talking, upright-walking and somewhat smarter ape. MLP
Myth – junk DNA isn’t junk after all Once the vast majority of our DNA was dismissed as junk, but now we know it is important – or so you might have read recently. In fact, it still appears likely that 85 to 95 per cent of our DNA is indeed useless. While many bits of DNA that do not code for proteins are turning out to have some function or other, this was predicted by some all along, and the overall proportion of our DNA with a proven function remains tiny
Faster and faster, but not better and better – yet One of the most tangible benefits of the human genome project is that sequencing genomes is getting much faster and cheaper. When it began, DNA sequencing was still largely a manual process. A highly skilled worker might manage 10,000 DNA letters, or base pairs, per day if all went well – which it seldom did. The latest automated instruments can generate up to 100 million base pairs of raw sequence data each day. If you have a little cash to spare, you can now get your genome sequenced by Illumina for less than $20,000. Once, the aim was the $1000 genome. Today, talk is already turning to the $100 genome.
The advances in speed, however, have come at a cost. Only short stretches of DNA can be sequenced at a time, so the pieces have to be joined together by looking for overlaps between them. While early instruments sequenced pieces up to 900 base pairs long, most high-speed machines produce “reads” of less than 100 base pairs. That means the overlaps are much shorter, making it far harder to join the pieces together, so assemblers use existing genomes as a guide – which can lead to mistakes. What’s more, we have two copies of all or almost all chromosomes, one from each parent. With short reads, it is impossible
to work out the individual sequence of each of the two copies – but for some medical purposes, it is important to have both. The next generation of sequencers should change this. The idea behind the leading contenders is to spy on the natural enzymes that replicate DNA by adding complementary bases to one strand of DNA. With the help of bases with fluorescent labels, the sequence can be read off as the DNA is replicated. Such machines should eventually be able to produce extremely long reads many thousands of base pairs long, greatly improving the quality of assembled genomes. MLP
> 19 June 2010 | NewScientist | 35
Nonintelligent design The list of regulatory RNAs grows longer by the day. In some cases, though, it is the act of making RNA rather than the product that matters: producing an RNA copy of one DNA strand chemically alters the proteins around which DNA is wrapped, shutting down genes on the opposite strand. Such convoluted mechanisms might seem odd and rather wasteful, but that is just what we should expect. “You sometimes ask yourself, ‘Why on earth is biology working this way?’,” says Birney. “But from evolution’s perspective it doesn’t have to look good in a textbook, it just has to work.” Unfortunately, it only has to work in some of us. The Byzantine complexity and nonintelligent design of our genomes means there is an awful lot that can go wrong, and all too often it does, argues John Avise of the University of California, Irvine. Splicing mistakes and errant microRNAs play a role in some cancers, for instance. On the bright side, discoveries like siRNA could lead to potent new treatments for all kinds of diseases. What’s certain is that there is much more to discover. “The genome is the start, not the end of the process,” says Birney. Michael Le Page
Evolution’s secrets You may be part Neanderthal – one of the many revelations about us emerging from genome sequencing. “It is revolutionising the way that we think about the evolution of humans,” says anthropologist John Hawks of the University of Wisconsin-Madison. Genomes provide a huge amount of information compared with fossils alone. The DNA in every organism is the latest link in an unbroken chain stretching back more than 3 billion years to the very dawn of life, changing a little with each generation. So by comparing the genomes of different people and animals – sometimes long-dead ones – it’s possible to work out what changed, and even when and where. Genome studies suggest, for instance, that some modern humans interbred not only with Neanderthals but also with other Homo species after they left Africa. And far from slowing down recently, human evolution began accelerating around 40,000 years ago
and has been speeding up ever since, Hawks has shown. The reason? A bigger population produces more potentially beneficial mutations, while the rise of farming and city living are exerting novel selective pressures. For example, gene variants that allow some adults to digest milk first appeared 7000 years ago, around the time that cattle were domesticated. It is possible to trace not just variants but also when and how genes first evolved. For example, the syncytin gene, which plays a crucial role in pregnancy, was originally acquired from a virus – one of many examples of gene transfer between different species. At the moment, we don’t understand the significance of the vast majority of the differences between genomes. Over the coming decades, however, we will be able to pinpoint the precise mutations that turned our tree-living ancestor into a naked, talking, upright-walking and somewhat smarter ape. MLP
Myth – junk DNA isn’t junk after all Once the vast majority of our DNA was dismissed as junk, but now we know it is important – or so you might have read recently. In fact, it still appears likely that 85 to 95 per cent of our DNA is indeed useless. While many bits of DNA that do not code for proteins are turning out to have some function or other, this was predicted by some all along, and the overall proportion of our DNA with a proven function remains tiny
Faster and faster, but not better and better – yet One of the most tangible benefits of the human genome project is that sequencing genomes is getting much faster and cheaper. When it began, DNA sequencing was still largely a manual process. A highly skilled worker might manage 10,000 DNA letters, or base pairs, per day if all went well – which it seldom did. The latest automated instruments can generate up to 100 million base pairs of raw sequence data each day. If you have a little cash to spare, you can now get your genome sequenced by Illumina for less than $20,000. Once, the aim was the $1000 genome. Today, talk is already turning to the $100 genome.
The advances in speed, however, have come at a cost. Only short stretches of DNA can be sequenced at a time, so the pieces have to be joined together by looking for overlaps between them. While early instruments sequenced pieces up to 900 base pairs long, most high-speed machines produce “reads” of less than 100 base pairs. That means the overlaps are much shorter, making it far harder to join the pieces together, so assemblers use existing genomes as a guide – which can lead to mistakes. What’s more, we have two copies of all or almost all chromosomes, one from each parent. With short reads, it is impossible
to work out the individual sequence of each of the two copies – but for some medical purposes, it is important to have both. The next generation of sequencers should change this. The idea behind the leading contenders is to spy on the natural enzymes that replicate DNA by adding complementary bases to one strand of DNA. With the help of bases with fluorescent labels, the sequence can be read off as the DNA is replicated. Such machines should eventually be able to produce extremely long reads many thousands of base pairs long, greatly improving the quality of assembled genomes. MLP
> 19 June 2010 | NewScientist | 35