Saturday, April 18, 2015

Evolution Sweeps Away Diversity

Natural selection carries off a large portion of neutral genetic diversity in large populations.

One would expect that large populations accumulate much more genetic diversity than small ones, over time. But if you watch those nature shows about herds of wildebeest roving over the Serengeti, it is very hard to see that variation. They behave as one, and look highly similar. Indeed, contrary to naive theory, larger populations tend not to have proportionately more genetic diversity than small ones. Why? The classical equilibrium law of population genetics assumes that larger populations naturally would have more variation, proportional to the number of members and the lengths of their various separate lineages. To balance this out, it also takes longer for any single new mutation to spread through such a population, so the ultimate rate of fixation of new mutations is no faster in large populations that it is in small ones.
"Under the assumptions of the neutral model of molecular evolution, the amount of variation present in a population should be directly proportional to the size of the population. However, this prediction does not tally with real-life observations: levels of genetic diversity are found to be substantially more uniform, even among species with widely differing population sizes, than expected."

But empirically, this expected high level of variation has not been true, even for neutral (unselected) alleles. This difference between theory and reality has been termed a paradox, and a recent paper (review) recounts the arguments above, showing that it is natural selection which constantly clears off accumulated variation, including completely neutral alleles that have no selective effect at all. This paper is not the first to address this whole paradox theoretically, but is the first to give an definitive quantitative solution.
"We show that genomic signature of natural selection is pervasive across most species, and that the amount of linked neutral variation removed by selection correlates with proxies for population size. We propose that pervasive natural selection constrains neutral diversity and provides an explanation for why neutral diversity does not scale as expected with population size."

Comparison of two species, one with large population size (fruit fly, A) and one with very small population size (Przwalski's horse, B). The gray dots are estimates drawn from 500k basepair windows across each genome of the local recombination rate (X axis), which can vary a great deal along chromosomes, and the local level of mutation and variation (Y axis). In a completely neutral theory, these measures should not correlate with each other (red line). The model developed in the paper is shown in the blue lines, where in a large population with lots of selection going on, regions with relatively low recombination show dramatically less variation, consistent with the rare selected mutation in those areas (whether positively or negatively selected) carrying a large number of neutral alleles with them, either to fixation (positive selection) or to their demise.

The issue is one of linkage. Imagine a long chromosome, with lots of genes and mutations. If one of those mutations is bad, then all the other mutations near it will be carried along with the bad one into oblivion, even if they did no harm themselves. The degree of linkage is a matter of the local recombination rate. Some areas of our genome recombine much faster than other areas, and thus allow more fine (selective) separation between nearby mutations, as they end up in different gametes and individuals due to the recombination that happens during meiosis.

So these researchers took a census of multiple genomes from many different species, (63 billion sequencing reads in all), measuring local recombination rates and mutation rates. They found that the bigger the species' population, the more clearly the prediction of correlation between the two measures came out in the data. Thus fruit flies, with a vast natural population, have roughly two-thirds the genetic diversity one would naively expect. The rest seems to have ended up shot down, innocent victims standing a little too close to more deleterious mutations.

In smaller populations, selection is just as fierce, but the level of neutral genetic diversity isn't expected to be as large in the first place, so loss by random drift plays a stronger role than loss as a byproduct of selection.

Humans are an good example. Now we are a huge population, but in genetic terms, we are practically clones compared to most other species. This is mostly because we were a very small population not long ago, and have only reached seven billion in an evolutionary eyeblink. So we have the genetics of a small population. But even in small populations, selection will have this diversity reducing effect, at a lower level. The intense selective evolution we went through over the millions of years prior not only kept populations small, but spread attractive and advantageous features through the population, at the expense of some of the other variation that was lying about.

In a way, this is an explanation for why species remain coherent entities through time. Their genetic diversity doesn't just grow endlessly into genetic chaos, but stays centered, in some abstract sense. Recombination and mating keep the genetic elements of the population continually mixing in a cloud of closely related forms, but it is selection that trims the outliers, both neutral and deleterious, keeping the cloud coherent, even as it also moves the entire cloud in new directions over the evolutionary landscape.

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  • Keynes on inequality, interest, the lower bound, and demand.
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  • "Redistribution", or justice?

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