Genetic hitchhiking is thought to be an inevitable result of strong
positive selection in a population. The basic idea is that if a particular gene is strongly selected for (as opposed to selected against), then the chunk of the genome that carries that gene will become very common in the population. The result is a local loss of genetic diversity: all (or nearly all) of the individuals in the population will have that same chunk of genetic information, whereas before the selection process acted, there might have been a lot of
variation in that chunk throughout the population. And this means that areas of the human genome that are less variable between people are suspected sites of recent positive selection. Within that chunk, there are potentially many genes and genetic elements that became more common in the population by virtue of their placement near the gene that was actually selected for. Those other genes are the hitchhikers. And it's likely that some hitchhikers are bad news – they're harmful mutations that would normally become rare or extinct in the population, but instead have become common by hitchhiking.
In the last few years, large amounts of genetic information have become available that have enabled biologists to look for evidence of such phenomena in the human genome. Specifically, two major projects have collected genetic data for the purpose of analyzing genetic variation among humans. One project, the International HapMap Project, mapped and quantified sites in the human genome that are known to vary among humans by a single genetic letter. These sites are called single nucleotide polymorphisms, or SNPs (pronounced "snips"). The project has mapped millions of these sites in a group of 270 humans representing various lineages. Another project that has made the news recently is the 1000 Genomes Project, which also seeks to provide a picture of human genetic variation using more people (more than 1000 at present) and slightly different technology. Efforts like these have taken analysis of the human genome to a new level. No longer do we merely wonder what "the" human genome is like – we can begin to learn about how genetic differences give rise to biological differences such as susceptibility to particular diseases.
23 September 2011
Harmful genes, and sneaky, too: Genetic hitchhiking in the human genome
22 September 2011
New limbs from old fins, part 3
The third installment of my series at BioLogos is now up. It discusses the developmental mechanisms that underlie the construction of limbs, and the striking fact that these mechanisms are the same ones used to construct fish fins. Watch for an appearance by Sonic Hedgehog.
19 September 2011
Genetic hitchhiking in English
The next post will discuss recent evidence for genetic hitchhiking in humans. So, what do we mean when we say that genes can hitchhike? To make sense of this phenomenon, we
first need to review chromosomes and sexual reproduction.
Most people know that sexual
reproduction creates offspring that are genetically distinct from
both of the their parents. That's true, but the genetic scrambling
that occurs is more significant than is sometimes reported. Let's
start by looking at chromosomes.
Like every other animal (or plant or pretty much any other organism),
your genetic endowment is carried in chunks of DNA called
chromosomes. You have 23 of these chunks, which are rather like
volumes in a set of encyclopedias. More completely, you have 23 pairs
of these volumes; one set was contributed by your mother and the
other by your father. Each of your parents had a complete set, also
consisting of a set from Mom and a set from Dad. When your mother
made the egg that became the zygote that became you, she provided you
with one copy of each volume in the set, and she chose those copies
randomly. For example, she may have chosen her dad's copy of
chromosome 1, but her mom's copy of chromosome 2. Just by virtue of
this random picking process, she made an egg with a shuffled version
of her own genetic cards. Dad did the same when he made his sperm,
and so your genetic complement is an amalgamation of your parents'
genomes which were amalgamations of your grandparents' genomes, and
so on.
16 September 2011
New limbs from old fins, part 2
The first post at BioLogos outlined limb structure and some historical background. The series at BioLogos was spawned by an idea here at QoD, which aimed to discuss some new findings in the fins-to-limbs story. Those new findings will be discussed in the fifth installment of the series at BioLogos.
Please comment! You can leave comments here or at BioLogos.
13 September 2011
"The stamp of one defect": an endless series on harmful mutations
Not surprisingly, Hamlet weighed in on the nature vs. nurture question, at least once.
So, oft it chances in particular men,
That for some vicious mole of nature in them,
As, in their birth,―wherein they are not guilty,
Since nature cannot choose his origin,―
By the o’ergrowth of some complexion,
Oft breaking down the pales and forts of reason,
Or by some habit that too much o’er-leavens
The form of plausive manners; that these men,
Carrying, I say, the stamp of one defect,
Being nature’s livery, or fortune’s star,
Their virtues else, be they as pure as grace,
As infinite as man may undergo,
Shall in the general censure take corruption
From that particular fault: the dram of eale
Doth all the noble substance of a doubt,
To his own scandal.
– Hamlet, Act I, Scene IV, The Oxford Shakespeare
It is certainly true that "the stamp of one defect" can wreak havoc on the scale that Hamlet describes, and whether the result is a debilitating physical limitation or damage to "the pales and forts of reason," the outcome is tragic by any measure.
08 September 2011
New limbs from old fins, part 1
Last month, I started a series on the topic of limb evolution, here at Quintessence of Dust. That series has been transformed (through a series of intermediates) into a series of posts at the BioLogos site. The first installment is now up, and it provides an expanded introduction to the topic and a little historical context. Subsequent posts will tackle fossils, developmental biology, genetics, the explanatory role of design, and related themes.
So go check out the introduction, and feel free to contribute comments, questions and suggestions here. And enjoy the image below, from Wellcome Images, which is featured in the post at BioLogos. Cool, huh?
08 August 2011
Molecular evolution: improve a protein by weakening it
In 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...
"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?
31 July 2011
Evolution cheats, or how to get an old enzyme to do new tricks
It is of course a cliche to state that eukaryotic cells (i.e., cells that are not bacteria) are complex. In the case of an animal, tens of thousands of proteins engage in fantastically elaborate interactions that somehow coax a single cell into generating a unique and magnificent organism. These interactions are often portrayed as exquisitely precise, using metaphorical images such as 'lock-and-key' and employing diagrams that resemble subway maps.
Many of these interacting proteins are enzymes that modify other proteins, and many of those enzymes are of a particular type called kinases. Kinases do just one thing: they attach phosphate groups to other molecules. This kind of modification is centrally important in cell biology, and one way to tell is to look at how many kinases there are: the human genome contains about 500 kinase genes.
Now, kinases tend to be pretty picky about who they stick phosphate onto, and this specificity is known to involve the business end of the kinase, called the active site. The active site is (generally) the part of the kinase that physically interacts with the target and transfers the phosphate. You might think that this interaction, between kinase and target, through the active site, would be by far the most important factor in determining the specificity of kinase function. But that's probably not the case.
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