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January 30, 2009

Inferring details of past evolution from DNA is tricky

Last week I discussed one of many papers that use the ratio of protein-changing to "neutral" genetic changes, along the branches of an evolutionary tree, to infer past natural selection. This week's paper presents data calling that approach into question. This does not necessarily undermine the overall conclusions of last week's paper, which were based on a variety of methods, including testing the actual performance of mutant proteins.

"Hotspots of biased nuclear substitutions in human genes" was published in PLoS Biology by Jonas Berglund and colleagues. I am not a molecular biologist, so will just summarize their main points. The paper is open access.

Most of our DNA does not code for proteins. Some of the noncoding DNA is known to have important regulatory functions. But there is lots of DNA whose function, if any, is unknown, but which is nonetheless highly similar among species, as if any change was lethal. Except, when someone tried deleting this DNA, a bit at a time, most of the deletions were not lethal or even (as far as they could tell) harmful. I discussed this work earlier.

Anyway, much of this noncoding DNA that differs little among most species is different in humans. Could these differences be what makes us different from other apes? Quite possibly. But are all these human-vs.-chimp differences important? Maybe not. An unexpectedly high fraction of the changes from the ape ancestor we share with chimps involved a change from A bound to T (a weak bond) to G bound to C (a strong bond). Unless noncoding DNA with stronger bonds is consistently better somehow (and only in humans!), this suggests that these changes are caused by some DNA-specific process and not by natural selection. In other words, these changes occurred whether or not they were beneficial, just as mutations do. Could similar AT=>GC changes have changed protein-coding sections of DNA?

The researchers compared 10,238 genes in humans, chimps, and macaques...

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September 06, 2008

Brief note on thumbs and junk DNA

I was going to write about this paper about a gene that evolved rapidly in humans since our lineage split from that leading to chimps. But Ed Yong at Not Exactly Rocket Science has already done a great post on it, including a picture showing its likely link to thumbs.

Comments on Ed's blog and a more complete treatment on Carl Zimmer's "The Loom" (both favorites of mine) point out the fallacy of some popular press coverage claiming this is the first evidence that "junk DNA" isn't junk after all. They both make the important point that we've known for decades that some DNA that doesn't code for protein is nonetheless very important.

On the other hand, lots of our DNA really does seem to be junk. Much of it is the product of "jumping genes" that copy themselves and insert themselves into existing DNA. These are common because they copy themselves, not because they do us any good (although, just by chance, they may occasionally be beneficial).

About 5% of DNA that doesn't code for protein is nonetheless "highly conserved", as if it were somehow beneficial and therefore maintained by natural selection. But a paper I reviewed earlier showed that much of this conserved noncoding DNA can be deleted without apparent ill effects. So if it's beneficial, it's not very beneficial. Or maybe it's beneficial only under special circumstances.

February 22, 2008

Looking for junk DNA?

Looking for my review of an article on "junk DNA"? It's here.

September 05, 2007

If it's junk, can we get rid of it?

This week's paper is "Deletion of ultraconserved elements yields viable mice" by Nadav Ahituv and collaborators, published online in PLoS Biology.

The instructions for "life as we know it" are coded in DNA, but it appears that only a fraction of our DNA is ever used. (This is probably not true of our brains, myths notwithstanding.) At least, only a fraction of it is ever translated into proteins such as enzymes. Some of the untranslated (noncoding) DNA has known functions, such as coding for the RNA part of the ribosomes that translate messenger RNA into protein, but much appears to be junk. Much of the junk is multiple copies of transposons, bits of unusually selfish DNA that reproduce like rabbits and burrow into the chromosomes, sometimes presumably disrupting functional DNA.

But if the noncoding DNA is mostly useless junk, why has some of it apparently been preserved by natural selection?

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June 14, 2007

A junkyard for natural selection?

A major paper was just published in Nature. “Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project� was written by a consortium involving contributions from many scientists. I will discuss a few of their more interesting findings, related to questions like "how much of our DNA doing something useful?"

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