As humans left Africa, about 70,000 years ago, they encountered new environments in Europe and Asia. Over the long course of adapting to these new environments, people in different regions evolved different features, particularly obvious in variations of the skin and hair.
The genetic basis for these variations in human appearance, and possible evolutionary reasons for these, are just beginning to be uncovered. In East Asia, and in the first populations that entered the Americas, a single nucleotide change in the EDAR gene, which encodes a signalling receptor, is largely responsible for causing hair to be thick and coarse in these regions. Using genetically altered mouse models (Mou et al., 2008) it has been possible to create this phenotype in rodents, and to delve further into the changes caused by this sequence alteration, informing approaches to try to understand why this gene variant was such an evolutionary advantage in ancient northern Asia. This first example explains some of the variation in appearance between peoples, but is only a small part of the overall picture.
This project will significantly advance knowledge of the basis and consequences human variation by generating new mouse models using CRISPR/Cas9 gene editing technology, informed by new findings in human genetics (Adhikari et al., 2016; Adhikari et al., 2015). The successful candidate will work with new gene edited mouse lines and assess the resulting alterations to hair and skin structure, as well as gene expression and protein functional changes following from the sequence alterations introduced. In particular, whether these sequence variants have any influence on disease incidence in mice, and so may underlie differences in human disease incidence, will be determined. This will generate an understanding of the genetic causes of human variation, an understanding of the potentially widespread effects of such genetic variants, and an opportunity to begin to understand the selective pressures that operated in different geographical regions during human evolution.
Training will include use of CRISPR/Cas9 mediated gene editing, histology and animal phenotyping, and modern molecular genetics, providing the successful candidate with opportunities for a career in evolution, human genetics, pathology or developmental biology.
The Roslin Institute is an outstanding location for this type of study, being fully equipped for gene editing, animal studies and phenotyping. The institute is part of the University of Edinburgh and is situated just to the south of the city.
Adhikari et al. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features. Nature Communications. 2016 7:10815.
Adhikari et al. A genome-wide association study identifies multiple loci for variation in human ear morphology. Nature Communications. 2015 6:7500.
Mou et al. Enhanced ectodysplasin-A receptor (EDAR) signaling alters multiple fiber characteristics to produce the East Asian hair form. Human Mutation. 2008 12:1405-11.