08 August 2011

Molecular evolution: improve a protein by weakening it

ResearchBlogging.orgIn the cartoon version of evolution that is often employed by critics of the theory, a new protein (B) can arise from an ancestral version (A) by stepwise evolution only if each of the intermediates between A and B are functional in some way (or at least not harmful). This sounds reasonable enough, and it's a good starting point for basic evolutionary reasoning.

But that simple version can lead one to believe that only those mutations that help a protein, or leave it mostly the same, can be proposed as intermediates in some postulated evolutionary trajectory. There are several reasons why that is a misleading simplification – there are in fact many ways in which a mutant gene or protein that seems to be partially disabled might nevertheless persist in a population or lineage. Here are two possibilities:

1. The partially disabled protein might be beneficial precisely because it's partially disabled. In other words, sometimes it can be valuable to turn down a protein's function.

2. The effects of the disabling mutations might be masked, partially or completely, by other mutations in the protein or its functional partners. In other words, some mutations can be crippling in one setting but not in another.

In work just published by Joe Thornton's lab at the University of Oregon, reconstruction of the likely evolutionary trajectory of a protein family (i.e., the steps that were probably followed during an evolutionary change) points to both of those explanations, and illustrates the increasing power of experimental analyses in molecular evolution.

03 August 2011

Let's see a show of autopods. Part 1.

The discovery of deep homology was a milestone in the history of evolutionary thought. Anatomical structures in distantly related organisms, structures with only the barest of functional similarities, were found to be constructed under the influence of remarkably similar genetic pathways. The original and classic example from 1989 involves genes controlling pattern in both insects and mammals – the famous Hox genes. Another great example emerged from the study of limb development and evolution in vertebrates, work beautifully described by Neil Shubin in Your Inner Fish.

The idea that the limbs of various animals are homologous – meaning that they are variations on a theme inherited from common ancestors – is certainly not new, with roots in the exploration of 'archetypes' by the great Sir Richard Owen. But deep homology goes, well, deeper, suggesting that even basic themes like 'limb' or 'eye' or even just 'thing-sticking-out-of-the-body-wall' can be identified and seen to be conserved throughout the biological world. And, importantly, deep homology points to genetic mechanisms that underlie basic themes, structural concepts so distinct that they would not be judged to be related by structural criteria alone. Consider, for example, limb development in vertebrates.

02 August 2011

What a selfish little piece of...

ResearchBlogging.org"The Selfish Gene." "Selfish DNA." Oh, how such phrases can get people bent out of shape.  Stephen Jay Gould hated such talk (see a little book called The Panda's Thumb), and Richard Dawkins devoted more time to answering critics of his use of the term 'selfish' than should have been necessary. Dawkins' thesis was pretty straightforward, and he provided real examples of "selfish" behavior of genes in both The Selfish Gene and its superior sequel, The Extended Phenotype. But there have always been critics who can't abide the notion of a gene behaving badly.

Leaving aside silly bickering about the attribution of selfishness or moral competence to little pieces of DNA, let's consider what we might mean if we tried to imagine a really selfish piece of DNA. I mean a completely self-centered, utterly narcissistic little piece of DNA, one that not only seeks its own interest but does so with rampant disregard for other pieces of DNA and even for the organism in which it travels. Can we imagine, for example, a piece of DNA that deliberately harms its host in order to propagate itself?