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Corante Blogs examine, through the eyes of leading observers, analysts, thinkers, and doers, critical themes and memes in technology, business, law, science, and culture.

The Press Will Be Outsourced Before Stopped

Vin Crosbie, on the challenges, financial and otherwise, that newspaper publishers are facing: "The real problem, Mr. Newspaperman, isn't that your content isn't online or isn't online with multimedia. It's your content. Specifically, it's what you report, which stories you publish, and how you publish them to people, who, by the way, have very different individual interests. The problem is the content you're giving them, stupid; not the platform its on."
by Vin Crosbie in Rebuilding Media

Travels In Numerica Deserta

There's a problem in the drug industry that people have recognized for some years, but we're not that much closer to dealing with it than we were then. We keep coming up with these technologies and techniques which seem as if they might be able to help us with some of our nastiest problems - I'm talking about genomics in all its guises, and metabolic profiling, and naturally the various high-throughput screening platforms, and others. But whether these are helping or not (and opinions sure do vary), one thing that they all have in common is that they generate enormous heaps of data.
by Derek Lowe in In the Pipeline

Disrobing the Emperor: The online “user experience” isn't much of one

Now that the Web labor market is saturated and Web design a static profession, it's not surprising that 'user experience' designers and researchers who've spent their careers online are looking for new worlds to conquer. Some are returning to the “old media” as directors and producers. More are now doing offline consulting (service experience design, social policy design, exhibition design, and so on) under the 'user experience' aegis. They argue that the lessons they've learned on the Web can be applied to phenomena in the physical and social worlds. But there are enormous differences...
by Bob Jacobson in Total Experience

Second Life: What are the real numbers?

Clay Shirky, in deconstructing Second Life hype: "Second Life is heading towards two million users. Except it isn’t, really... I suspect Second Life is largely a 'Try Me' virus, where reports of a strange and wonderful new thing draw the masses to log in and try it, but whose ability to retain anything but a fraction of those users is limited. The pattern of a Try Me virus is a rapid spread of first time users, most of whom drop out quickly, with most of the dropouts becoming immune to later use."
by Clay Shirky in Many-to-Many

The democratisation of everything

Over the last few years we've seen old barriers to creativity coming down, one after the other. New technologies and services makes it trivial to publish text, whether by blog or by print-on-demand. Digital photography has democratised a previously expensive hobby. And we're seeing the barriers to movie-making crumble, with affordable high-quality cameras and video hosting provided by YouTube or Google Video and their ilk... Music making has long been easy for anyone to engage in, but technology has made high-quality recording possible without specialised equipment, and the internet has revolutionised distribution, drastically disintermediating the music industry... What's left? Software maybe? Or maybe not."
by Suw Charman in Strange Attractor

RNA Interference: Film at Eleven

Derek Lowe on the news that the Nobel Prize for medicine has gone to Craig Mello and Andrew Fire for their breakthrough work: "RNA interference is probably going to have a long climb before it starts curing many diseases, because many of those problems are even tougher than usual in its case. That doesn't take away from the discovery, though, any more than the complications of off-target effects take away from it when you talk about RNAi's research uses in cell culture. The fact that RNA interference is trickier than it first looked, in vivo or in vitro, is only to be expected. What breakthrough isn't?"
by Derek Lowe in In the Pipeline

PVP and the Honorable Enemy

Andrew Phelps: "Recently my WoW guild has been having a bit of a debate on the merits of Player-vs.-Player (PvP) within Azeroth. My personal opinion on this is that PvP has its merits, and can be incredible fun, but the system within WoW is horridly, horribly broken. It takes into account the concept of the battle, but battle without consequence, without emotive context, and most importantly, without honor..."

From later in the piece: "When I talk about this with people (thus far anyway) I typically get one of two responses, either 'yeah, right on!' or 'hey, it’s war, and war isn’t honorable – grow the hell up'. There is a lot to be said for that argument – but the problem is that war in the real historical world has very different constraints that are utterly absent from fantasized worlds..."
by Andrew Phelps in Got Game

Rats Rule, Right?

Derek Lowe: "So, you're developing a drug candidate. You've settled on what looks like a good compound - it has the activity you want in your mouse model of the disease, it's not too hard to make, and it's not toxic. Everything looks fine. Except. . .one slight problem. Although the compound has good blood levels in the mouse and in the dog, in rats it's terrible. For some reason, it just doesn't get up there. Probably some foul metabolic pathway peculiar to rats (whose innards are adapted, after all, for dealing with every kind of garbage that comes along). So, is this a problem?.."
by Derek Lowe in In the Pipeline

Really BAD customer experience at Albertsons Market

Bob Jacobson, on shopping at his local Albertsons supermarket where he had "one of the worst customer experiences" of his life: "Say what you will about the Safeway chain or the Birkenstock billionaires who charge through the roof for Whole Foods' organic fare, they know how to create shopping environments that create a more pleasurable experience, at its best (as at Whole Foods) quite enjoyable. Even the warehouses like Costco and its smaller counterpart, Smart & Final, do just fine: they have no pretentions, but neither do they dump virtual garbage on the consumer merely to create another trivial revenue stream, all for the sake of promotions in the marketing department..."
by Strange Attractor in Total Experience

The Guardian's "Comment is Free"

Kevin Anderson: "First off, I want to say that I really admire the ambition of the Guardian Unlimited’s Comment is Free. It is one of the boldest statements made by any media company that participation needs to be central to a radical revamp of traditional content strategies... It is, therfore, not hugely surprising to find that Comment is Free is having a few teething troubles..."
by Kevin Anderson in strange
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

The Loom

« If These Lice Could Talk | Main | More on Common Ancestors »

October 11, 2004

Biting the Dust

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Posted by Carl Zimmer

In March, I wrote a post on some tantalizing new findings about the secrets of human evolution lurking in our genome. In brief, researchers at the University of Pennsylvania studied a gene called MYH16 that helps build jaw muscles in primates. In our own lineage, the gene has mutated and is no longer active in jaw muscles. Perhaps not coincidentally, we have much smaller, weaker jaws than other apes. The researchers estimated that the gene shut down around 2.4 million years ago--right around the time when hominid brains began to expand. They suggested that shrinking jaw muscles opened up room in the hominid head for a larger brain.

It's a cool hypothesis, but it may not hold up. Scientists at Arizona State University have followed up on the initial study by anlayzing much larger pieces of MYH16, both in humans and in other species. All told, they studied 25 times more DNA from the gene. In a paper in press at Molecular Biology and Evolution, they report finding a significantly different date for when the gene mutated. Instead of 2.4 million years ago, they get a much older date: 5.3 million years ago.

If that's true, then you can forget any significant link between the evolution of MYH16 and brain evolution. If the Arizona State team is right, the two events are separated by three million years. What's more, the jaws of hominids also remained relatively large after the mutation of MYH16.

The Arizona State researchers do point out an intriguing clue that may eventually lead to a solution to this paradox. The mutation that the Penn team originally argued that the MYH16 gene became useless when a section of DNA in the middle of its sequence was accidentally deleted. Often, when this sort of deletion takes place, DNA-copying enzymes come to a screeching halt at the site of the mutation. With the gene only partly copied, it cannot be turned into a protein. But the Arizona State researchers found signs that the gene did not shut down entirely 5.3 million years ago. The DNA "downstream" from the mutation--in other words, beyond the point where the enzymes stopped copying the gene--has picked up mutations in a pattern that shows no sign of natural selection at work. That's what you'd expect from DNA that doesn't make a gene, since any change will have no effect for good or bad on its owner. But the upstream DNA--the part of the gene that could still be copied--told a different story. It showed signs of having undergone selection. So perhaps the mutation that occurred 5.3 million years ago didn't actually kill the gene, but just amputated it. What the surviving portion of MYH16 did (or still does) remains unknown.

I would wager that this new paper will unfortunately not attract much press. When scientists first come up with an attention-grabbing hypothesis, they're more likely to get a paper accepted to a high-profile journal, and more likely still to get written up by science writers like me. But follow-up work often ends up in the shadows.

That's a shame, because science is actually not made up of single studies that suddenly overturn everything that came before. It's more of a dialectic, as different groups of scientists search for new evidence in order to put hypotheses to new tests. Some hypotheses--such as the idea that chimpanzees are our closest living relatives--have become stronger over time. Others fall away. It would help if more people understood this process. Unfortunately, it seems that a lot of people think science is like building an elaborate sculpture out of glass. If someone discovers that a piece of research is wrong, then it seems as if the whole sculpture cracks and falls to the ground. Creationists are particularly fond of this tactic. They seize on research about evolution that goes against earlier research, and claim that the entire theory of evolution is a fraud. They conveniently ignore all points on which scientists agree. So, for example, the researchers who have published the new findings on MYH16 do not conclude that humans were intelligently designed, MYH16 and all. Instead, they argue that the gene mutated earlier than once believed, and that the full history of this gene remains to be revealed. Science is more like a sculpture made of clay than glass, continually being molded and reshaped to better reflect reality.

Correction, 10/16/04: Changed "ancestors" to "relatives."

Comments (9) + TrackBacks (0) | Category: Evolution


COMMENTS

1. Susan on October 13, 2004 02:39 PM writes...

"But the upstream DNA--the part of the gene that could still be copied--told a different story. It showed signs of having undergone selection."

Can you elaborate on this (or point me somewhere, book or Internet, that explains)? What are the "signs of having undergone selection"?

Thanks.

Permalink to Comment

2. gaw3 on October 13, 2004 02:45 PM writes...

Fantastic post, as is all of the writing on this site! I tried writing a non-technical description of GLUD2 which probably originated by retrotransposition during a time of hominid specialization. I ended up pretty tongue-tied- so now I REALLY admire your efforts!!

Permalink to Comment

3. Carl Zimmer on October 13, 2004 02:50 PM writes...

There are a number of ways of measuring natural selection on DNA. For example, one way takes advantage of the fact that only some of the "letters" in a gene are actually used to make a protein. So a mutation to this "coding DNA" can have a positive or negative effect on its owner, while a mutation to "non-coding" DNA is almost certain to have no effect. If a gene evolves without strong selection, you'd expect that the coding and non-coding DNA would have acquired equal levels of mutations. If selection is at work, the ratio will not be the same. So, for example, if natural selection favors new versions of the gene, you'd expect more change in coding DNA vs non-coding DNA. Scientists can measure these ratios by comparing versions of the same gene in different species.

Permalink to Comment

4. Susan on October 14, 2004 05:32 PM writes...

The answers lead to more questions ...

Does a mutation to coding DNA ever have 'no effect'?
(Is it possible to tell?)

Does selection ever 'react neutrally' to a mutation? (for example, gene undergoes mutation, codes protein differently, organism as a whole unaffected in terms of interaction with environment)?

Thanks again. I have always loved biology, and I really appreciate this opportunity to learn :)

Permalink to Comment

5. Stan Lyness on October 15, 2004 10:40 PM writes...

Yes, fantastic post & great blog, thanks so much. Maybe here instead of "the idea that chimpanzees are our closest living ancestors" you want to say "closest living relatives"? Regardless of how chimpy the common ancestors may have been, living chimps aren't ancestors.

Permalink to Comment

6. Steve Reuland on October 18, 2004 10:13 PM writes...

"Often, when this sort of deletion takes place, DNA-copying enzymes come to a screeching halt at the site of the mutation. With the gene only partly copied, it cannot be turned into a protein."

Just a nit-pick here, but a truncated protein would be the result of a premature termination codon. That wouldn't send any DNA or RNA copying enzymes to a halt; instead, the nascent polypeptide chain being formed on the ribosome would stop synthesis prematurely.

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7. Steve Reuland on October 18, 2004 10:28 PM writes...

Susan:

What are the "signs of having undergone selection"?

If the ratio of nonsynonymous to synonymous mutations (dN/dS) is significantly greater or less than 1, it's a sign of selection. A synonymous mutation is one that doesn't change the amino acid sequence of the resulting protein, so we know it's neutral. A nonsynonymous mutation changes the amino acid sequence, and may be beneficial, detrimental, or neutral. If nonsynonymous mutations are being preserved at a greater rate than neutral mutations (when dN/dS > 1), then natural selection must favor the nonsynonymous mutations, indicating positive selection. This means amino acid sequence is evolving in a particular direction. If nonsynonymous mutations are being preserved less often than neutral mutations (when dN/dS against, which indicates purifying selection. That means selection is keeping the amino acid sequence the same. When the rates are the same (dS/dN = 1), then there is no selection. The gene in question is therefore in a state of neutral drift, and probably doesn't do anything important, at least not anymore.

Does a mutation to coding DNA ever have 'no effect'? (Is it possible to tell?)

Oh, certainly. Most mutations will not have any effect. For one thing, there are synonymous mutations, which won't change the amino acid sequence. And then even if the amino acid sequence is changed, many (if not most) mutations won't affect the protein's function, since a lot of amino acids aren't critical, and others can be replaced with similar amino acids without any effect.

Permalink to Comment

8. Steve Reuland on October 18, 2004 10:33 PM writes...

Oops, there was a little truncation there (premature stop codon?)

To recap:

dN/dS > 1: positive selection

dN/dS

dN/dS = 1: neutral drift

Basically the same thing Carl already said, but I had to get nerdy about it.

Permalink to Comment

9. Steve Reuland on October 18, 2004 10:34 PM writes...

Arrgh, it did it again. Someone doesn't like my "less than" sign.

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