Exploring the impact of Neanderthal sequence contribution to muscle function and health

Neanderthals appeared in the fossil record about 350.000 years ago and mainly lived in Europe and western Asia and became extinct around 30.000 years ago. Anatomically they had bodies more robust, with a larger muscle mass than those of present-day humans. Neanderthal sequences also contribute to several features related to lipid metabolism, including risk of T2D. Approximately 2% of the genome of present-day non-Africans is inherited from Neanderthals and when comparing present-day human genomes with extinct archaic hominin genomes (i.e. Neanderthal and Denisovan) there are 31,389 single-nucleotide positions where all present-day humans carry a derived allele, whereas the archaic hominin genomes all carry the ancestral allele (including 96 amino acids substitutions). These derived alleles have, in evolutionary terms, increased rapidly in frequency in present-day humans and they have a high probability to be causal and associated with important phenotypes. However, this previous analysis, was based on the 1000G data set, and using a much larger sampling frame (i.e. n = 10.000 from the Botnia study) opens the possibility to identify individuals carrying low frequency ancestral alleles, thus providing an opportunity to study these genotype-phenotype relationships. We are currently investigating two of these variants in relation to metabolic function.