Gene linkage as a tool to detect positive selection on genes

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Whenever we think about evolution it’s always easier to think of it in a macroscopic perspective. It’s quite easy to grasp evolution actions looking at visible traits such as behaviours, skin color or disease resistance. But we have to understand that every traits is produced by one or a collection of genes working at the microscopic level.

As a consequence of this, generally it can be elementary to understand which trait in unders positive selection, i.e. favored by selection because it brings advantage to the organism carrying it. You can just look at the increase in the frequency of the trait in the next generatioin: if it’s positive selected, it will more and more frequent. But at the same time it can be really hard to catch which genes are under positive selection. If a trait is caused by a collectoion of genes (like most of the cases) it’s really complicate to relate the rise in frequency to the positive selection on genes.

This is why I want to talk about an evolutionary tool that can allow us to find positive selected genes by looking at gene linkage.

linkage-1
it’s pretty easy to understand what gene likage is. If two genes are close together, the chance of getting a crossing-over between them is pretty low; thus they will get heredited almost always together.

If you now consider one allele for a given gene. Every allele at a certain position in the genome is linked with some other genes (or markers) close by. Theory predicts that the chance of crossing-over between that allele and any of the markers increases with the distance between allele and marker. So, of course, if you have the allele and a marker very far away from each other, after one generation these two will be unlinked. But if they’re very close, many many generations have to pass before the two are broken free.

Hence, if a new allele is born in a given position in the genome (by any kind of mutation for example), just for the fact of its birth, it would be linked to some markers. You can look at evolutionary trees of that allele and see which marker is still linked to it or is not. We expect the linkage to be pretty high for a new allele and almost zero for an old allele. Thus if we measure the linkage of a give allele (by counting how many markers are still linked to it) and we find out that it’s pretty high then we know that the allele was born recently.

Now lastly, consider the allele frequency. If you have a new allele you expect it to be fairly rare in the population. On contrast if you have a high frequency gene you can’t really tell if it’s due to positive selection or many other mechanisms (such as linkage itself: another gene could drive the high frequency of another one). Thus, if we find an allele at high frequencies with a high linkage, we can conclude that that gene is under positive selection.

As one of my professor says, “Confusing enough??” Let me tell you another story…

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