Dataset Information

Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.

ABSTRACT: 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.

SUBMITTER: Scheinfeldt LB

PROVIDER: S-EPMC2734137 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.

Scheinfeldt Laura B LB Biswas Shameek S Madeoy Jennifer J Connelly Caitlin F CF Schadt Eric E EE Akey Joshua M JM

Molecular biology and evolution 20090311 6

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 ...[more]

PMID: 19279085

Similar Datasets

Project description:BACKGROUND: Levels of differentiation among populations depend both on demographic and selective factors: genetic drift and local adaptation increase population differentiation, which is eroded by gene flow and balancing selection. We describe here the genomic distribution and the properties of genomic regions with unusually high and low levels of population differentiation in humans to assess the influence of selective and neutral processes on human genetic structure. METHODS: Individual SNPs of the Human Genome Diversity Panel (HGDP) showing significantly high or low levels of population differentiation were detected under a hierarchical-island model (HIM). A Hidden Markov Model allowed us to detect genomic regions or islands of high or low population differentiation. RESULTS: Under the HIM, only 1.5% of all SNPs are significant at the 1% level, but their genomic spatial distribution is significantly non-random. We find evidence that local adaptation shaped high-differentiation islands, as they are enriched for non-synonymous SNPs and overlap with previously identified candidate regions for positive selection. Moreover there is a negative relationship between the size of islands and recombination rate, which is stronger for islands overlapping with genes. Gene ontology analysis supports the role of diet as a major selective pressure in those highly differentiated islands. Low-differentiation islands are also enriched for non-synonymous SNPs, and contain an overly high proportion of genes belonging to the 'Oncogenesis' biological process. CONCLUSIONS: Even though selection seems to be acting in shaping islands of high population differentiation, neutral demographic processes might have promoted the appearance of some genomic islands since i) as much as 20% of islands are in non-genic regions ii) these non-genic islands are on average two times shorter than genic islands, suggesting a more rapid erosion by recombination, and iii) most loci are strongly differentiated between Africans and non-Africans, a result consistent with known human demographic history.

Dataset Information

Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.

Publications

Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets