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Recent human adaptation: genomic approaches, interpretation and insights

Key Points

  • The availability of genomic data has spurred the development of methods for genome-wide neutrality tests.

  • Genome-wide scans for selection have been applied to a variety of data sets that were collected from global population samples.

  • Both integrative studies that incorporated phenotypic data and regulatory variation, and functional follow-up studies of candidate adaptive variants have increased our understanding of how putatively adaptive genetic variation affects the phenotypic variation that may have a role in reproductive fitness.

  • There are several limitations to these approaches, such as false-positive signatures of adaptation.

  • Other issues include the limited models of adaptation (primarily the classic selective sweep) that have been incorporated into genome-wide scans for selection.

  • The most comprehensive examples of human adaptation studies take advantage of genome-wide genetic variation with phenotypic data and functional follow-up data to elucidate the role of genetic variants in reproductive fitness in recent human history.

Abstract

The recent availability of genomic data has spurred many genome-wide studies of human adaptation in different populations worldwide. Such studies have provided insights into novel candidate genes and pathways that are putatively involved in adaptation to different environments, diets and disease prevalence. However, much work is needed to translate these results into candidate adaptive variants that are biologically interpretable. In this Review, we discuss methods that may help to identify true biological signals of selection and studies that incorporate complementary phenotypic and functional data. We conclude with recommendations for future studies that focus on opportunities to use integrative genomics methodologies in human adaptation studies.

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Figure 1: Genetic signatures of positive selection.
Figure 2: An abridged hypoxia-inducible factor 1 pathway.
Figure 3: Data integration approaches.

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Acknowledgements

The authors thank S. Soi and J. Lachance for their discussions and suggestions. This work was funded by the US National Institutes of Health (NIH) Pioneer Award (DP1OD0644S), the NIH (R01GM076637) and the US National Science Foundation Hominid grant (BCS0827436) to S.A.T.

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Correspondence to Laura B. Scheinfeldt or Sarah A. Tishkoff.

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Glossary

Reproductive fitness

A measure of how well an organism survives and reproduces; it is generally determined by the genetic contribution of an individual to the gene pool of the next generation.

Gene pathways

Sets of interacting gene products that are related to particular functions, including signalling and metabolic pathways.

Demographic history

The study of population-level changes over time, including changes in population size, migration, and gene flow between populations.

International HapMap Project

A publically available genome-wide data set of common single nucleotide polymorphisms generated from global populations.

Linkage disequilibrium

The non-random association of two or more genetic variants.

Positive selection

A type of natural selection in which a trait that increases reproductive fitness becomes more common over time in a population.

FST

A statistical measure of population structure based on differences in variant frequencies between populations using genotypic data.

Locus-specific branch length

A measure of population structure in one population sample relative to two other population samples based on FST values; it is useful for identifying population-specific adaptation.

Haplotype

A set of genetic variants that are inherited together on a single chromosome.

Convergent evolution

The independent evolution of similar phenotypic traits.

Locus

A region of the genome that contains a particular gene or genetic sequence.

Pygmy

Typically used in the genetic literature to refer to an individual member of a population in which the average male and female stature is <150 cm and <140 cm, respectively. Historically, the term has been used in a pejorative manner; however, some recent populations that culturally identify themselves as Pygmies have revived the term themselves.

Pleiotropic

Pertaining to a gene: affecting multiple phenotypes.

Epigenetic

Pertaining to an inherited phenotypic change: caused by mechanisms other than changes in the underlying DNA sequence, such as DNA methylation or histone modification.

Metabolomic

Pertaining to the metabolome, which is the combined set of metabolites that are present in a given tissue at a given time.

Transcriptomic

Pertaining to the transcriptome, which is the combined set of RNA transcripts that are present in a given tissue at a given time.

Expression quantitative trait loci

Regions of the genome containing genetic polymorphisms that either alter or are in linkage disequilibrium with variants which affect gene regulation to influence the levels of RNA or protein produced.

Enhancers

Regulatory DNA elements that usually bind several transcription factors; they can activate transcription at long distances from the promoter and in an orientation-independent manner.

DNase I-hypersensitive sites

Genetic regions that are sensitive to the DNase I enzyme. These are important regulatory regions because they are available for binding by gene-regulatory proteins.

Induced pluripotent stem cells

Somatically derived cells that have been synthetically induced to behave as pluripotent stem cells.

Integrative genomics

The integration of data from multiple 'omics' platforms.

QST

A statistical measure of population structure or differences in quantitative trait measurements between populations using phenotypic data.

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Scheinfeldt, L., Tishkoff, S. Recent human adaptation: genomic approaches, interpretation and insights. Nat Rev Genet 14, 692–702 (2013). https://doi.org/10.1038/nrg3604

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