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.

But before the random picking process occurred in the steps leading up to the final egg/sperm, something remarkable happened to further shuffle the genetic deck. For each chromosome, the different copies lined up with each other and exchanged contents. In other words, a new chromosome 1 was made that was an amalgamation of the maternal chromosome 1 and the paternal chromosome 1. The two new versions were chromosomes unlike any in your mom or dad; they were new creations, clearly designed to maximize the diversity in your genetic inheritance. This process, which is illustrated in the diagram below, is called crossing over.


The figure shows two instances of crossing over, creating the amalgamations that are part white, part black. In the real process, crossing over can occur at multiple sites along the chromosome, so that the resulting amalgamations are black-white-black-white and so on.

What this means is that you received, from each of your parents, a set of chromosomes that included at least some which were shuffled versions of their own chromosomes. And more importantly, this means that the units of genetic material that you received were much bigger than individual genes (which can barely be visibly represented on a diagram like the one above) but typically smaller than an entire chromosome. It's as if you were given a set of encyclopedias in which individual volumes had chapters from one version of that volume and chapters from another. Individual genes would be merely pages. The basic lesson here is that you received your genes from your parents in chunks, like chapters, and not one by one, like pages.

What does this have to do with hitchhiking? Well, suppose that in one of those chapters, meaning in one section of one chromosome, there appeared a beneficial mutation of some kind, and suppose that this mutation conferred an advantage on every individual who carried it. Over a relatively short time (evolutionarily speaking), that chapter could become a lot more common in the population. It may even become so common that it's the norm, in which case it would be considered to be fixed in the population. (The process is then called fixation.) Notice, importantly, that we said the chapter will become fixed. Why not just the gene? Because the pieces of DNA that are passed down in each generation are a lot bigger than that, as we just saw.

The basic message, then, is this: when an organism inherits some new and beneficial gene, it inherits everything in the vicinity of that gene as well. If that new and beneficial gene becomes fixed in the population, then everything in the vicinity will be fixed as well. The result is that when a strong selection process acts, and drives a new gene to fixation in a relatively short time, it leaves a mark on the genome: one chapter in the set of encyclopedias will be oddly the same in everyone. That chapter will display a lot less genetic diversity than other chapters. That's the signature of recent positive selection, resulting from a so-called selective sweep. And it results in the fixation of a lot of stuff, most of which is just along for the ride by virtue of being located in the same chapter as the beneficial gene. All that other stuff got there by hitchhiking.


Image credit: Wikipedia. Image is from T.H. Morgan, A Critique of the theory of evolution (1916).

6 comments:

Berend de Boer said...

Steve: The basic lesson here is that you received your genes from your parents in chunks, like chapters, and not one by one, like pages.
The implication is that errors get copied too, i.e. any error which does not lead to immediate death. As it is likely there are more errors than improvements, wouldn't this be an argument that the genes deteriorate quicker than they can improve?

John Farrell said...

That
chapter will display a lot less genetic diversity than other
chapters. That's the signature of recent positive selection,
resulting from a so-called selective sweep.


Steve, how many specimens would a researcher need to check for those chapters showing a lot less diversity, to be confident he/she has got evidence of a selective sweep? I'm guessing it depends on the species, but is there a rough number for say, a fish species, or species of bird?

SteveMatheson said...

Good question. Statistically, it probably doesn't matter much whether you're talking about a fish or a bird or a human. You just need enough samples to be able to detect variation. I'm guessing hundreds at least. The human HapMap, which is a map of small-scale variants in the human genome, is made from 270 people (so far). That map was used to detect traces of positive selection in a 2007 paper you can get free online at the HapMap project site.

Now, those studies were looking for genomic locales with low variation. If you already knew where you wanted to look, say in the vicinity of a candidate gene, then you might not need hundreds of samples to detect low diversity. But scores at least, I'm guessing.

SteveMatheson said...

That argument is simplistic and unsupported by the data. The main weakness in the argument, I think, is the assumption that mutations are mostly deleterious. That's not a good assumption. Most are neutral. The other weakness in the argument is that it ignores purifying selection. Hitchhiking can bring mildly deleterious alleles along for the ride, but the ride isn't free and it doesn't last forever.

More importantly, genomic analyses haven't detected the phenomenon that your hypothesis predicts; namely, ongoing "deterioration" of genes. Genes come and go, to be sure, but if I'm not mistaken your hypothesis applies globally and makes predictions that are unsupported by the evidence.That's not to say that genomic "deterioration" of some sort can't happen. Michael Lynch has proposed that this is indeed happening in developed societies due to the relaxation of purifying selection (by modern medicine).

Mike Blyth said...

Is this question related to or the same idea as Müller's ratchet? It's not something I understand very well, but isn't the idea that accumulation of deleterious mutations will gradually decrease fitness in the absence of a way to restore the good copies? I've read that both horizontal gene transfer and sexual reproduction exist in part to solve this problem. True or controversial?

SteveMatheson said...

All true. Muller's ratchet is about genetic load: in relatively small populations, deleterious mutations can get fixed, and then the population is stuck with them. They can accumulate, and with no way for the deleterious mutation to be isolated as an evolutionary unit, they can accumulate to the point that the lineage (species) goes extinct. Recombination is one solution to this problem, and gene transfer is another. I think that in gigantic populations, the ratchet is much slower (or even nonexistent), because it's a lot harder to fix a deleterious mutation.