May 21, 2010

It's not all junk -- and it evolves!

We've known for a long time that most human DNA doesn't code for protein, that much of that noncoding DNA is junk (former genes that no longer do anything, multiple copies of selfish "jumping DNA", etc.), but that some noncoding DNA performs useful functions. Click "junk DNA" at right for past posts on this topic. This week's paper, Adaptive Evolution of an sRNA That Controls Myxococcus Development (published in Science by Yuen-Tsu N. Yu, Xi Yuan, and Gregory J. Velicer), is an example of how such functions can evolve.

Myxococcus xanthus is a "social bacterium", whose behavior somewhat resembles that of the "social amoeba", Dictyostelium. When starved, the individual bacterial cells get together in a mound and form spores. Previously, Velicer's group found a mutant that doesn't do this. Then a second mutation arose in that line that restored the original behavior. Now they report the molecular basis for this restored spore-forming ability. The product of the key gene turns out to be small RNA molecule. Its normal function is apparently to block aggregation and spore formation, except when starved. The new mutation essentially knocks out this function, restoring the ability to make spores, but without the normal link to starvation.

May 15, 2010

Evolution of DNA methylation in animals, plants, and fungi

This week, I will try to explain what DNA methylation is and some of the reasons why it's important, before discussing this week's paper on how DNA methylation has evolved.

The paper is "Genome-Wide Evolutionary Analysis of Eukaryotic DNA Methylation", published in Science by Assaf Zemach and others from the lab of Daniel Zilberman.

DNA methylation usually refers to the attachment of a methyl (CH3) group to a cytosine, one of four DNA bases (C, in DNA's A,T,C,G alphabet). Here's a link showing one way cytidine can get methylated. And this Wikipedia article shows cytosine in place in double-stranded RNA. (DNA would be similar, but with T instead of U.)

The functions of DNA methylation mostly come from the reduced transcription of RNA from methylated stretches of DNA. Surprisingly, when a new DNA copy is made (e.g., when one of our cells divide), methylation patterns are generally copied, too. Together, these two facts explain many of DNA methylation's functions.

First, DNA methylation is key to imprinting, whereby genes inherited from one parent are often shut down, perhaps for life, by methylation. Imprinting often reflects an unconscious battle between male and female parents over whether to maximize growth of this particular offspring, whatever the consequences for the mother's future survival and reproduction, or take or more long-term view. Earlier, I discussed the possible role of imprinting in mental illness.

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September 4, 2009

Where do new genes come from?

When a few members of a family have a gene not found in most other members, one explanation is that the gene is newly evolved, rather than inherited from the common ancestor of that family. (The other possibility is that their ancestor had it, but most descendants lost it.)

New genes often turn out to be copies of old genes, sometimes with modifications that give them very different functions. But a paper just published in Current Biology reports "Emergence of a new gene from an intergenic region", rather than duplication of an existing gene....

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August 5, 2009

Highly conserved, but how important?

Today Pharyngula takes a break from his exhaustive documentation of the existence of wackos and evil-doers among religious and political conservatives -- who would have guessed? -- to discuss highly conserved non(protein)coding DNA. It seems reasonable that if a DNA sequence is highly similar between humans and fish, whose last common ancestors lived way back in the good old days, then it's probably doing something important. But a paper I discussed earlier showed that highly conserved noncoding regions can sometimes be deleted without any apparent ill effects. Of course, this is also true of some protein-coding genes; we apparently have a lot of backups. Actually I'm not sure computer and circuit-board analogies are that useful.

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 6, 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 5, 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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