Toomas Kivisild
2011 - 2016 • Starting Grant
How has receiving an ERC grant influenced you as a scientist?
The ERC grant helped me consolidate my research group and establish a Laboratory of Human Evolutionary Genetics at the University of Cambridge. It enabled me to carry out research that would not have been possible with smaller grants. Generation of the project data helped me establish a broad global network of collaborations that I am still benefitting from today.
An inter-disciplinary approach for identifying evolutionary active regions in the human genome
Humans have been successful in the course of evolution because of their ability to adapt to their environment. Evidence points to Africa as the main playground of our species for most of its evolutionary history. Over the past 100,000 years, humans have dispersed globally and been repeatedly challenged to cope with the diverse range of natural environments and climate, as well as the shift from a non-sedentary lifestyle to a food-producing settled way of life in the last 10,000 years. How adapted to their environment are humans today? The aim of this project was to reveal which parts of our genome have experienced the highest degree of change recently, making it possible to identify those aspects of our biology that are most maladapted to our modern environments. These goals were achieved by focusing on the aspects of human adaptation to climate, nutrition, and lifestyle in different regions of the world.
Results
Amongst Siberian populations, three different ancestry profiles were detected. Applied selection scans helped to determine the initial catalogue of selection candidate genes, and the most likely causative mutation in CPT1A gene, which is involved in fatty acid metabolism, was identified.
The results on Andean populations revealed that the studied high-altitude groups (>4000 m and >2000 m) share a common ancestry that is distinct from lowland populations. Both groups showed signatures of selection in hypoxia- and vasoconstriction-related genes.
The study of the Mikea, the last known hunter-gatherer population in Madagascar, found no support to the hypothesis according to which they descend from a population that existed before the arrival of Austronesian and Bantu agriculturalists. As all three populations are derived from the same admixture event, they probably adopted their way of life through cultural reversion.
Impact
The project generated new whole genome sequence data that are now being widely used as a reference data set for the study of genetic variation across the globe. The results of population structure and demographic history analyses represent contributions to new knowledge about the genetic history of different regions of the world. The analyses of selection have highlighted a number of genes that have functional relevance to the study of metabolic pathways and related diseases.
For example, the highlighted genetic variant found in Siberian populations is associated with a defect in metabolism of long-chain fatty acids as a target of positive selection. This mutation, linked with high infant mortality in Inuits, is likely to carry a fitness-increasing effect in Arctic populations. The project team was able to explain why a disease mutation is common in a population through adaptation in their ancestry.