|Title||Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Scheinfeldt, LB, Biswas, S, Madeoy, J, Connelly, CF, Schadt, EE, Akey, JM|
|Journal||Molecular biology and evolution|
|Date Published||2009 Jun|
|Keywords||asia, diabetes, europe, population ġenetics, population structure, positive selection, theory|
Mutations in the human gene ALMS1 result in Alström Syndrome, which presents with early childhood obesity and insulin resistance leading to Type 2 diabetes. Previous genomewide scans for selection in the HapMap data based on linkage disequilibrium and population structure suggest that ALMS1 was subject to recent positive selection. Through a detailed population genomic analysis of existing genomewide data sets and new resequencing data obtained in geographically diverse populations, we find that the signature of selection at ALMS1 is considerably more complex than what would be expected for an idealized model of a selective sweep acting on a newly arisen advantageous mutation. Specifically, we observed three highly divergent and globally dispersed haplogroups, two of which carry a set of seven derived nonsynonymous single nucleotide polymorphisms that are nearly fixed in Asian populations. Our data suggest that the interaction of human demographic history and positive selection on standing variation in Eurasian populations approximately 15 thousand years ago parsimoniously explains the spectrum of extant ALMS1 variation. These results provide new insights into the evolutionary history of ALMS1 in humans and suggest that selective events identified in genomewide scans may be more complex than currently appreciated.
|Alternate Journal||Mol. Biol. Evol.|
Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.
For years, I've worked on their bones. Now I'm working on their genes. Read more about the science studying these ancient people.
From a finger bone of an ancient human came the record of a completely unexpected population. My lab is working on the science of the Denisova genome.
The advent of agriculture caused natural selection to speed up greatly in humans. We're uncovering some of the ways that populations have rapidly changed during the last 10,000 years.