Akey, Joshua M.

Shriver, Mark D.

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Joshua eAkey

Mark eShriver

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A grand challenge in evolutionary and population genetics: New paradigms for exploring the past and charting the future in the post-genomic era

Joshua M. Akey

Mark D. Shriver

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Although genome-wide scans for positive 
selection have now become routine in many 
organisms (Akey, 2009), these studies have 
yielded little information into the precise 
mechanistic basis of how natural and domes-
ticated populations evolve. Indeed, a recent 
study suggests that selection acting on newly 
arisen advantageous mutations has been sur-
prisingly rare in recent human evolutionary 
history (Hernandez et al., 2011). If selec-
tion in humans does not abide by this clas-
sic model of adaptive evolution, then what 
selective models are consistent with the data? 
Previous candidate gene analyses provide a 
glimpse into the types of complexity that 
await more detailed analyses, such as selec-
tion from standing variation (Enattah et al., 
2008; Magalon et al., 2008; Scheinfeldt et al., 
2009), evidence for both directional and bal-
ancing selection acting on the same locus 
(Tishkoff et al., 2001; Verrelli et al., 2002), 
and epistatic selection (Williams et al., 2005). 
Additionally, with the advent of growing 
databases of sex hormone enhancer elements 
perhaps we are finally poised to approach the 
role of sexual selection on the genomic level 
(e.g., McLean et al., 2011). Thus, an ongoing 
major challenge in evolutionary and popula-
tion genetics is to delineate more precisely 
the tempo and mode of adaptive evolution 
and to study the similarities and differences 
in adaptive trajectories between species and 
how these are influenced by population 
demographic history.
More fundamentally, new insights about 
basic biological mechanisms have provoked 
calls that the modern synthesis needs to be 
expanded (e.g., Kutschera and Niklas, 2004; 
Pigliucci, 2007 and references therein). For 
instance, how does the evolution of evolv-
ability, epigenetic inheritance, phenotypic 
plasticity, and the origins of complexity 
(reviewed in Pigliucci, 2007) fit, if at all, 
into the modern synthesis? Although the 
relevance of these ideas to the need for an 
A grand challenge in evolutionary and population genetics: 
new paradigms for exploring the past and charting the future 
in the post-genomic era
Joshua M. Akey1* and Mark D. Shriver 2*
1 Department of Genome Sciences, University of Washington, Seattle, WA, USA
2 Department of Anthropology, Pennsylvania State University, University Park, PA, USA
*Correspondence: akeyj@u.washington.edu; mds17@psu.edu
functional genomics technologies such as 
ChiP-SEQ and RNA-SEQ, and systematic 
catalogs of gene deletions in a variety of 
model organisms are examples of projects 
that can and should inform the study of 
evolutionary genetics broadly.
The future of evolutionary and popula-
tion genetics is simultaneously exciting and 
daunting. It is exciting because we are in the 
early stages of having massively large and 
powerful data sets to address fundamen-
tal questions about the forces that shape 
patterns of genetic variation within and 
between species. It is daunting because the 
methodological tools and theoretical mod-
els needed to interpret these data sets are 
still in their infancy. In the following, we 
articulate some of the most pressing chal-
lenges confronting evolutionary and popu-
lation genetics.
An obvious challenge is the analysis 
and interpretation of (the current) next- 
generation sequencing technologies, which 
have democratized whole-genome sequenc-
ing. At long last, individual laboratories can 
accomplish projects that were once the sole 
purview of large-scale sequencing centers 
(Shendure and Hanlee, 2008).Whole-
genome sequence data are now available 
for hundreds of species and are being gen-
erated in thousands of individuals from 
particular populations. Whole-genome 
sequence data can open new windows on 
the evolutionary process, such as descrip-
tions of sex-biased dispersal and mutation 
rate biases (e.g., Wilson Sayres et al., 2011). 
Not even extinction is a guarantee against 
having one’s genome sequenced or one’s 
mating habits analyzed (e.g., Green et al., 
2010; Reich et al., 2010). Nor is extinc-
tion necessarily a guarantee against being 
resurrected. Moreover, the hope that such 
sequencing projects might help forest all the 
extinction of endangered species also shines 
bright (e.g., Miller et al., 2011).
New doors to a deeper understanding of 
the evolutionary and population genetics 
of life have been opened through recent 
technological, informational, and compu-
tational advances. Over the past decade we 
have seen molecular biology and computa-
tional capacities increase by several orders 
of magnitude. In some important ways the 
science and study of evolutionary genet-
ics today is between paradigms. Like some 
100 years ago after the rediscovery and con-
firmation of Mendel’s genetics, but before 
the emergence of population genetics and 
the modern synthesis, today we are working 
in the immediate post-genomic time, find-
ing ourselves on the precipice of a mature 
or synthetic understanding of evolutionary 
genetics and genomics. Molecular and other 
technologies are being developed at an ever-
increasing rate, and it is hard to keep abreast 
of all the new methods. Likewise, databases 
and statistical methods are advancing and 
growing rapidly.
Approaches to evolutionary studies such 
as ancient DNA and single-cell molecu-
lar biology, which once held promise but 
had fallen by the wayside due to technical 
limitations, are being revitalized and are 
changing the way we think about what can 
be studied. For example, although genome-
wide association studies (GWAS) have not 
led to the identification of many genes of 
large effect, it has helped facilitate person-
alized disease-risk estimation through new 
methods focused on combining the smaller 
effects from many independent loci. These 
methods facilitate trait value prediction 
and represent a powerful tool for identify-
ing novel pathways of disease and pheno-
typic variation (de los Campos et al., 2010). 
Evolutionary and population geneticists 
also benefit from a growing understanding 
of the functional, phenotypic, and medi-
cal effects of genetic variation. GWAS on 
disease and non-disease traits, burgeoning 
www.frontiersin.org July 2011 | Volume 2 | Article 47 | 1
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Citation: Akey JM and Shriver MD (2011) A grand 
challenge in evolutionary and population genetics: new 
paradigms for exploring the past and charting the future 
in the post-genomic era. Front. Gene. 2:47. doi: 10.3389/
fgene.2011.00047
This article was submitted to Frontiers in Evolutionary and 
Population Genetics, a specialty of Frontiers in Genetics.
Copyright © 2011 Akey and Shriver. This is an open-access 
article subject to a non-exclusive license between the authors 
and Frontiers Media SA, which permits use, distribution 
and reproduction in other forums, provided the original 
authors and source are credited and other Frontiers condi-
tions are complied with.
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expanded modern synthesis is controversial 
(Pennisi, 2008), they should not be categori-
cally dismissed. Rather, such ideas should be 
subjected to rigorous and systematic study, 
and their contribution to evolutionary pro-
cesses and relationships with currently held 
evolutionary paradigms should be investi-
gated on a case-by-case basis.
Fulfilling the promise of evolution-
ary and population genetics will require 
approaches that increasingly leverage and 
apply knowledge gleaned across disciplines 
in novel, creative, and ultimately insight-
ful ways. Likewise, evolutionary genetic 
approaches can and should contribute to 
our general understanding of the life sci-
ences from anatomy to zoology. Finally, 
over the next few years, as the genealogical 
genetics, nutragenomics, and personalized 
disease-risk genotyping industries expand 
into a more mature era of personal genom-
ics, evolutionary, and population geneticists 
can and should help facilitate an informed 
interpretation of these data. Failing to do so, 
preferring “pure science” to public engage-
ment will be to our collective loss. Our goal is 
for Frontiers in Evolutionary and Population 
Genetics to be an interdisciplinary forum for 
addressing these issues and more.
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Akey and Shriver Evolution and population genetics
Frontiers in Genetics | Evolutionary and Population Genetics  July 2011 | Volume 2 | Article 47 | 2


A Grand Challenge in Evolutionary and Population Genetics: New Paradigms for Exploring the Past and Charting the Future in the Post-Genomic era

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A Grand Challenge in Evolutionary and Population Genetics: New Paradigms for Exploring the Past and Charting the Future in the Post-Genomic era

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