Debunking myths on genetics and DNA

Wednesday, January 25, 2012

Surfing the wave of genetics: the man who invented genetic landscapes

Today is the 90th birthday of the one and only Luigi Luca Cavalli-Sforza, professor emeritus at Stanford University and a pillar in population genetics. Oh, and in case you couldn't tell by the name, he's Italian, too. Not that I'm biased, mind you.

Cavalli-Sforza is best known for his book The History and Geography of Human Genes, in which he reconstructs the history of human migrations by mapping the distribution of gene alleles and correlating gene frequencies in populations with the geographic distances between them.

I had an interesting discussion a few months ago and it occurred to me then that many people outside the field of genetics still think that all traits are selected through evolution. This is not true. If you remember, another famous population geneticist came up with a mathematical model according to which it would take 300 generations for a trait under constant selection pressure to completely take over. That lead to Haldane's dilemma and the fact that such time scale was too slow to explain all genetic variation observed today.

The fact that Haldane's model didn't fit the observations eventually lead to the neutral theory of molecular evolution, and one of the greatest players in this new thinking was Motoo Kimura. Kimura's theory of "random genetic drift" is based on the assumption that most mutations are free of selective effects, and hence the rate of molecular evolution is determined by the mutation rate. This is backed up by the fact that most mutations we see are "silent" (which means they bear no effect on the proteins) and that most of the DNA in eukaryotes is non-coding.

Genetic drift is the change in allele frequencies due to chance. Under selection, some individuals pass their genes onto the next generation because they are "fitter." However, if not all traits are under selection, the vast majority is driven by chance. Some individuals will have offsprings, others won't, and each generation represents a new random drawing in the gene pool. When a random mutation arises in a population, assuming the mutation is neutral (in other words it doesn't affect the fitness of the individuals), the chance that it will get fixed in the population by random drift is 1/N where N is the population size. Therefore, the smaller the population, the greater the chance that a random mutation becomes prevalent by "chance" (and not selection!).

To celebrate Cavalli-Sforza's birthday, I chose a paper published in 2009 [1] that looks at genetic diversity in the Y chromosome and compares it to the expected variation under neutral drift. From the abstract:
"We observe geographic peculiarities with some Y chromosome mutants, most probably due to a drift-related phenomenon called the surfing effect. We also compare the overall genetic diversity in Y chromosome DNA data with that of other chromosomes and their expectations under drift and natural selection, as well as the rate of fall of diversity within populations known as the serial founder effect during the recent ‘‘Out of Africa’’ expansion of modern humans to the whole world. All these observations are difficult to explain without accepting a major relative role for drift in the course of human expansions."
The surfing effect is a really interesting phenomenon: mutations that arise in the wave front of an expanding population have an advantage over mutations that arise in individuals who are left behind with respect to the migrating portion of the population. This is because the front of the migration is a local, temporarily smaller population, and since the probability of a mutation to get fixed is inversely proportional to the population size, the fact that the mutants arise in a smaller population puts them at an advantage. Furthermore,
"The faster the population expansion, the greater the probability of success of a mutant that arises in the wave front, because then the wave front is longer."
In the paper, Chiaroni et al. look at the 18 major haplogroups (genetically similar groups that can be thought of as originating from the same ancestor) of Y chromosome genotypes and inferr their place of origin.
"If migrations were random, the geographic distribution of individuals with a specific haplogroup would be approximately normal (Gaussian) around the place of origin of the oldest mutation defining the haplogroup, apart from irregularities due to vagaries of the environment: obstacles, like mountains and deserts, or favored routes, like coasts and rivers."
The interesting finding in the paper is that while the expected genetic diversity for chromosome X more or less matches the observed one, the expected diversity of chromosome Y is significantly higher than the observed one indicating that, on average, there is more natural selection acting on X and the other autosome chromosomes than on the Y chromosome.

The authors conclude:
"The increasing role of human creativity and the fast diffusion of inventions seem to have favored cultural solutions for many of the problems encoun- tered in the expansion. We suggest that cultural evolution has been subrogating biologic evolution in providing natural selection advan- tages and reducing our dependence on genetic mutations, especially in the last phase of transition from food collection to food production."

[1] Chiaroni, J., Underhill, P., & Cavalli-Sforza, L. (2009). Y chromosome diversity, human expansion, drift, and cultural evolution Proceedings of the National Academy of Sciences, 106 (48), 20174-20179 DOI: 10.1073/pnas.0910803106

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