228
L. S. Emery and J. M. Akey
9.6
Conclusions
The study of human evolution sits poised on the cusp of a new and comprehensive
understanding of how natural selection and demographic history have influenced
human genetic variation. The past century has seen great strides in this endeavor,
including the description of the hitchhiking effect, background selection, and the
development of models to describe positive, negative, and balancing selection.
These developments have provided new and surprising insights into population
differentiation, the persistence of deleterious and disease-causing alleles, and
the peopling of the world. Studies of convergent evolution in disparate human
populations on such traits as lactase persistence and living at high altitudes have
exhibited the stochastic nature of adaptive evolution.
Empirical studies have provided an enormous body of knowledge on the signatures of selection across the human genome. These inferences show, for example,
that negative selection has been weak but pervasive across much of the genome.
Balancing selection has proven to be an important force at a handful of loci, with its
complex interaction between hitchhiking and background selection leaving unique
and striking patterns in patterns of local genetic variation. The influence of positive
selection has significantly influenced patterns of human genetic variation, both
directly and indirectly through genetic hitchhiking. Targets of adaptive evolution
are scattered across the human genome, affecting many gene processes, pathways,
and networks. Thus, human populations have adapted to their environments in ways
numerous and diverse (Hahn 2008).
Even in the face of these vast new areas of scientific knowledge, the bulk
of our insight into these topics is yet to come. Advances in next-generation
sequencing technology have enabled the sequencing of hundreds of thousands of
human genomes from increasingly diverse worldwide populations. Advances in
statistical methods for detecting the signatures of selection will improve sensitivity
and specificity of “candidate selected loci.” Additionally, the development of more
realistic models of selection will account for epistatic effects between genes,
selection from standing variation, recurrent mutation, and selection at CNVs, indels,
microsatellites, and other structural variants. Finally, armed with a detailed map of
the signatures of selection across the human genome, we will be able to delineate
the phenotypic consequences of adaptive evolution, make more accurate predictions
of genetic risk for individuals, and gain insights into the connection between human
populations and their evolutionary environments.
References
1000 Genomes Project Consortium (2010) A map of human genome variation from population -
422 scale sequencing. Nature 467:1061–1073
Ahmed Z, Riazuddin S, Bernstein SL et al (2001) Mutations of the protocadherin gene PCDH15
cause Usher syndrome type 1F. Am J Hum Genet 69:25–34. https://doi.org/10.1086/321277
L. S. Emery and J. M. Akey
9.6
Conclusions
The study of human evolution sits poised on the cusp of a new and comprehensive
understanding of how natural selection and demographic history have influenced
human genetic variation. The past century has seen great strides in this endeavor,
including the description of the hitchhiking effect, background selection, and the
development of models to describe positive, negative, and balancing selection.
These developments have provided new and surprising insights into population
differentiation, the persistence of deleterious and disease-causing alleles, and
the peopling of the world. Studies of convergent evolution in disparate human
populations on such traits as lactase persistence and living at high altitudes have
exhibited the stochastic nature of adaptive evolution.
Empirical studies have provided an enormous body of knowledge on the signatures of selection across the human genome. These inferences show, for example,
that negative selection has been weak but pervasive across much of the genome.
Balancing selection has proven to be an important force at a handful of loci, with its
complex interaction between hitchhiking and background selection leaving unique
and striking patterns in patterns of local genetic variation. The influence of positive
selection has significantly influenced patterns of human genetic variation, both
directly and indirectly through genetic hitchhiking. Targets of adaptive evolution
are scattered across the human genome, affecting many gene processes, pathways,
and networks. Thus, human populations have adapted to their environments in ways
numerous and diverse (Hahn 2008).
Even in the face of these vast new areas of scientific knowledge, the bulk
of our insight into these topics is yet to come. Advances in next-generation
sequencing technology have enabled the sequencing of hundreds of thousands of
human genomes from increasingly diverse worldwide populations. Advances in
statistical methods for detecting the signatures of selection will improve sensitivity
and specificity of “candidate selected loci.” Additionally, the development of more
realistic models of selection will account for epistatic effects between genes,
selection from standing variation, recurrent mutation, and selection at CNVs, indels,
microsatellites, and other structural variants. Finally, armed with a detailed map of
the signatures of selection across the human genome, we will be able to delineate
the phenotypic consequences of adaptive evolution, make more accurate predictions
of genetic risk for individuals, and gain insights into the connection between human
populations and their evolutionary environments.
References
1000 Genomes Project Consortium (2010) A map of human genome variation from population -
422 scale sequencing. Nature 467:1061–1073
Ahmed Z, Riazuddin S, Bernstein SL et al (2001) Mutations of the protocadherin gene PCDH15
cause Usher syndrome type 1F. Am J Hum Genet 69:25–34. https://doi.org/10.1086/321277