A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection

  title={A Composite of Multiple Signals Distinguishes Causal Variants in Regions of Positive Selection},
  author={Sharon R. Grossman and Ilya Shlyakhter and Elinor K. Karlsson and Elizabeth H Byrne and Shannon Morales and Gabriel Frieden and Elizabeth Hostetter and Elaine Angelino and Manuel Garber and Or Zuk and Eric S. Lander and Stephen F. Schaffner and Pardis C Sabeti},
  pages={883 - 886}
Pinpointing Genetic Selection The human genome contains hundreds of regions with evidence of recent positive natural selection, yet, for all but a handful of cases, the underlying advantageous mutation remains unknown. Current methods to detect the signal of selection often results in the identification of a broad genomic region containing many candidate regions that vary among individuals. By combining existing statistical methods, Grossman et al. (p. 883, published online 7 January) developed… 

Detecting and characterizing genomic signatures of positive selection in global populations.

Genome wide signals of pervasive positive selection in human evolution

The results establish that adaptation was frequent in human evolution and provide support for the hypothesis of King and Wilson (King and Wilson 1975) that adaptive divergence is primarily driven by regulatory changes.

Fine-mapping the Favored Mutation in a Positive Selective Sweep

iSAFE identified identical selected mutations in multiple non-African populations suggesting an out-of-Africa onset of selection in these regions, all of which involve pigmentation related genes.

Statistical methods for detecting natural selection from genomic data.

In the study of molecular and phenotypic evolution, understanding the relative importance of random genetic drift and positive selection as the mechanisms for driving divergences between populations

Exploration of signals of positive selection derived from genotype-based human genome scans using re-sequencing data

Re-sequencing of two ~300 kb regions lacking known targets of selection in HapMap CHB individuals provided strong evidence for positive selection within each and suggested the micro-RNA gene hsa-miR-548c as the best candidate target in one region, and changes in regulation of the sperm protein gene SPAG6 in the other.

Using Population Genomics to Detect Selection in Natural Populations: Key Concepts and Methodological Considerations

The conceptual framework of population genomics is outlined, genomic patterns of variation are related to evolutionary processes, and major biological factors to be considered in studies of selection are identified.

Detecting recent positive selection with high accuracy and reliability by conditional coalescent tree.

A novel method based on conditional coalescent tree to detect recent positive selection by counting unbalanced mutations on coalescent gene genealogies is developed, which is more robust than many other approaches against biases due to various demographic effects, including population bottleneck, expansion, or stratification.

Signatures of positive selection apparent in a small sample of human exomes.

Exome sequences, which comprise all protein-coding regions, are promising data sets for studies of natural selection because they offer unbiased genome-wide estimates of polymorphism while focusing

Aberrant Time to Most Recent Common Ancestor as a Signature of Natural Selection.

An anomaly detection algorithm using distributions of pairwise time to most recent common ancestor (TMRCA) to simultaneously detect multiple modes of natural selection in whole-genome sequences, which is applied to the Complete Genomics diversity panel and recovers loci previously inferred to be under positive or balancing selection.

A model-based approach for identifying signatures of balancing selection in genetic data

Two composite likelihood ratio tests for detecting balancing selection are developed that outperform competing methods under a variety of assumptions and demographic models and are able to reproduce many previously-hypothesized signals of balancing selection as well as discover novel interesting candidates.



A Map of Recent Positive Selection in the Human Genome

A set of SNPs is developed that can be used to tag the strongest ∼250 signals of recent selection in each population, and it is found that by some measures the authors' strongest signals of selection are from the Yoruba population.

Genome-wide detection and characterization of positive selection in human populations

‘Long-range haplotype’ methods, which were developed to identify alleles segregating in a population that have undergone recent selection, and new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population are developed.

Constructing genomic maps of positive selection in humans: where do we go from here?

The recent history of the burgeoning field of human population genomics is chronicle, genome-wide scans for positive selection in humans are critically assessed, important gaps in knowledge are identified, and both short- and long-term strategies for traversing the path from the low-resolution, incomplete, and error-prone maps of selection today to the ultimate goal of a detailed molecular, mechanistic, phenotypic, and population genetics characterization of adaptive alleles are discussed.

Positive Natural Selection in the Human Lineage

Positive natural selection is the force that drives the increase in prevalence of advantageous traits, and it has played a central role in our development as a species. Until recently, the study of

How reliable are empirical genomic scans for selective sweeps?

This work considered a coalescent model of directional selection in a sensible demographic setting, allowing for selection on standing variation as well as on a new mutation, and concluded that, insofar as attributes of the beneficial mutation affect the power to detect targets of selection, genomic scans will yield an unrepresentative subset of loci that contribute to adaptations.

Localizing Recent Adaptive Evolution in the Human Genome

It is found that recent adaptation is strikingly pervasive in the human genome, with as much as 10% of the genome affected by linkage to a selective sweep.

Calibrating a coalescent simulation of human genome sequence variation.

The first calibrated population genetic model is presented and it is shown that, while still arbitrary, it successfully generates simulated data that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation.

A second generation human haplotype map of over 3.1 million SNPs

The Phase II HapMap is described, which characterizes over 3.1 million human single nucleotide polymorphisms genotyped in 270 individuals from four geographically diverse populations and includes 25–35% of common SNP variation in the populations surveyed, and increased differentiation at non-synonymous, compared to synonymous, SNPs is demonstrated.

Molecular genetics of human pigmentation diversity.

  • R. Sturm
  • Biology
    Human molecular genetics
  • 2009
From a culmination of genetic and functional studies, it is apparent that a number of genes impacting melanosome biogenesis or the melanin biosynthetic pathway are candidates to explain the diversity seen in human pigmentation.


The purpose of this discussion is to offer some unity to various estimation formulae and to point out that correlations of genes in structured populations, with which F-statistics are concerned, are expressed very conveniently with a set of parameters treated by Cockerham (1 969, 1973).