The second to last day of Biology of Genomes is now over, and instead of the usual late night set of talks, last night we were treated to a “lobster buffet”, followed by “all genome-nerd band” Ethidium Spill, lead by Francis Collins. As always, you can follow live coverage via twitter at #BG2011, and you can also read Matthew Herper’s thoughts at the Forbes blog.
The quality of all the talks remains very high, but today I am only going to write about two. What I liked about both of these talks was the link between recent human evolution, geography and phenotype-associated traits, despite being two very different methodologies.
Selection for height in Europeans
Europeans differ systematically in their height, and these differences correlate with latitude. The average Italian is 171cm, whereas the average Swede is a full 4cm taller. Are these differences genetic? Have they been under evolutionary selection in recent human history?
Michael Turchin gave some pretty convincing answers to these questions, using genetic data from the 129 thousand individuals in the GIANT consortium. He compared the frequencies of alleles that are known to increase height, and found that they are more common in Northern Europe. Interestingly, he found the same relationship for alleles that have weaker evidence for height association, showing that there are still a large number of common height variants hiding in the genome, which are also more frequent in Northern Europe.
Height differences are thus heritable, but have they been under evolutionary selection? Or are these differences merely down to genetic drift? This can also be tested using the GIANT data, which shows significant statistical evidence of selection on height variants in recent history. On top of that, the magnitude of the selection is correlated with the effect size of the height variant, providing strong evidence that these variants are being selected specifically for their impact on height.
This is a textbook example of how an evolutionary study should be done; you show a phenotypic difference exists, that it is heritable, and that it is under selection. This opens the question as to why height has been selected in Northern Europe (or shortness in Southern Europe). Could the same data be used to test specific hypotheses there?
Partial selective sweeps and parallel evolution
One theme of the day was the complexity of selection in humans; you do not see very many of the clean, classical selective sweeps that you see in Drosophila. Graham Coop has tied this observation to another complexity of human diversity, that of allelic heterogeneity. This is when one trait-associated gene can contain multiple separate causative alleles which have arisen at different times. Perhaps the reason we do not see classical sweeps is because there are often many different mutations being selected in parallel?
Graham’s talk had the distinction of being the only one of the whole conference based only on theoretical work, with no genetic data. He presented a model of parallel evolution through partial selective sweeps, a model of mutation, migration and selection through space. Interestingly, the mathematics of the model is actually equivalent to a model of crystallization from physics.
The dynamics are pretty intuitive. Mutations arise randomly across geographic space. The first mutation to arise sees a significant selective advantage, and spreads as a selective sweep. Other mutations then arise: if they occur within the spread of the first mutation, they offer no advantage and thus are unlikely to spread, but if they arise outside of the existing mutation’s territory, then they start new sweeps. Eventually, these sweeps meet, and where they meet each loses the selective advantage, stopping both. From that point on, the mutations start to mix much slower under drift and migration, and at the end you have a number of different alleles under different haplotype backgrounds, with partial spatial structure
You can define a characteristic length, as a function of the population density, selective co-efficient, dispersal and mutation rates, which is the mean distance that a sweep travels for before it hits another. If the space available for sweeps is larger than this, it is likely you will see partial sweeps and allelic heterogeneity. Using some reasonable parameter values, taken from the hemoglobin mutations that confer resistance of malaria, Graham showed that we would expect to see frequent parallel evolution for malarial resistance, consistent with the high allelic heterogeneity we see in Africa.
Thank you to both Michael Turchin and Graham Coop for allowing me to write about their work. The image above shows malarial endemicity across Africa, and was made by the Malaria Atlas Project