SummaryA new study identifies gene duplication of a salivary enzyme as a recent adaptation to changes in diet among human populations, highlighting the diverse ways that gene regulation can evolve

Coyne, Jerry A.

Hoekstra, Hopi E.

Elsevier - Publisher Connector 

it! This has challenged our
predictions of how sexual conflict
could influence the evolution of
genital morphology — until now.
The new study of the African bed
bug, Afrocimex constrictus
(Cimicidae) by Reinhardt et al. [3],
exemplifies the extreme and
somewhat bizarre consequences
of arms races between males and
females.
In A. constrictus, as in all
Cimicids, females have responded
to traumatic insemination from
males by evolving ‘paragenitalia
sinuses’. These are structural
modifications of the abdominal
cavity, which develop in addition to
their ‘normal’ genitalia [11]. These
paragenitalia sinuses guide the
male intromittent organ into an
organ called the mesospermalege,
which is packed with immune
cells or haemocytes. The whole
structure functions to localize the
site of insemination and reduce the
physical trauma of insemination.
Interestingly, in A. constrictus,
males mimic females by also
having paragenitalia sinuses,
although the male form is slightly
different to that of the female,
with a more open morphology
that exposes the site of piercing.
To further confuse the issue, some
females in this species appear to
mimic the male expression of the
paragenitalia sinuses by exhibiting
the male open-form.
To gain insight into the selection
for paragenitalia in males and
polymorphic paragenitalia in
females in A. constrictus,
Reinhardt et al. [3] measured the
intensity of the scarring of
paragenital sinuses in males and
‘open’ and ‘closed’ morphs in
females. Males were found to
have fewer scars than females,
irrespective of morph. Cimicids
only appear to recognise gender
after genital contact, thus
Reinhardt et al. [3] suggest that
the distinct form of the male
paragenitalia (open) signals their
gender to other males and thereby
reduces the incidence of
male–male traumatic insemination.
In addition, females of the ‘open’
morph had fewer scars than
females of the ‘closed’ morph,
so that by mimicking males,
females appear to suffer less
male-induced harm.
The expression of sex-limited
traits in both sexes, more
commonly known as
cross-sexual transfer, is an
unusual but relatively widespread
phenomenon. However, the
revelation that A. constrictus are
polymorphic in both the form
(open or closed) and number of
their paragenitalia sinuses, is the
first documented account of
polymorphic female genitalia
within a species. The authors [3]
suggest that such genetic
differentiation in both male and
female traits has the potential to
result in speciation via sexual
conflict, as predicted by
recent theoretical
models [13,14].
Males emulating females, and
females emulating males: this
exciting new study blurs the battle
lines between the sexes in the
sexual competition arena.
Reinhardt et al. [3] show us that
genital evolution via sexual
conflict is more than a theoretical
possibility. The bottom line is that
the interactions between males
and females under sexual
conflict are likely to be as
important as male or female
biased processes — sperm
competition or cryptic female
choice — in shaping genital
morphology. Anyone for sexual
equality?
References
1. Hosken, D.J., and Stockley, P. (2004).
Sexual selection and genital evolution.
Trends Ecol. Evol. 19, 87–93.
2. Arnqvist, G. (1998). Comparative
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Gorb, S., and Siva-Jothy, M.T. (2007).
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12. Stutt, A.D., and Siva-Jothy, M.T. (2001).
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13. Gavrilets, S., and Waxman, D. (2002).
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Centre for Ecology and Conservation,
School of Biosciences, University of
Exeter, Cornwall Campus, Penryn
Cornwall, TR10 9EZ, UK.
E-mail: Z.Lewis@exeter.ac.uk
DOI: 10.1016/j.cub.2007.09.052
Current Biology Vol 17 No 23
R1014Evolution of Protein Expression:
New Genes for a New Diet
A new study identifies gene duplication of a salivary enzyme as a recent
adaptation to changes in diet among human populations, highlighting
the diverse ways that gene regulation can evolve.Jerry A. Coyne1
and Hopi E. Hoekstra2
Evolution is a contingent process,
dependent on the vagaries of the
environment, history, and whatever
mutations happen to appear.Consequently, there are few strict
‘laws’ of evolution; ours is instead
a science of generalizations. One
search for regularities has focused
on the molecular basis of
adaptation. A widespread but
somewhat controversial view is
Dispatch
R1015that important adaptations may
be due largely to changes in the
expression of rather than the
sequences of genes themselves
[1–3]. This idea was first proposed
by King and Wilson [4] to explain
large morphological changes
(but low divergence in protein
sequence) between humans and
chimpanzees.
With the rise of genomics and
its vast storehouse of DNA
sequences, work has intensified
to determine what sorts of
mutations cause adaptive
change. Much effort has been
focused on identifying mutations
that make us uniquely human (for
example [5,6]), or those that
differentiate human populations
from each other. A recent study by
Perry et al. [7] describes a novel
case of altered gene expression
that has evolved in response to
changes in human diet. This
result is exciting because it
identifies one of only a handful of
known genes whose differentiation
among populations of our species
was driven by natural selection.
The study also highlights the
diverse and unpredictable ways
that evolution can alter gene
expression.
In principle, changes in gene
regulation — which we define as
mutations that alter the amount,
timing, or location of a gene’s
expression — can occur in several
ways. These include changes in
amino-acid coding sequence of
genes, changes in the noncoding
sequences, or duplication/loss
of genes (Figure 1). While
speculation about the genetics of
adaptation has centered on the
relative importance of ‘structural’
mutations — those affecting
amino acid sequence of
proteins — versus cis-regulatory
mutations [1–3,8], the categories
shown in Figure 1 imply that this
dichotomy is too simplistic:
changes in protein sequence and
gene number can affect gene
expression as well. Indeed, the
work of Perry et al. [7] shows
that adaptive change in gene
expression was achieved by
repeated duplication of an
enzyme–coding locus.
One of the many differences
between humans and chimps is our
diet (we are far more omnivorous),cis-regulatory
elements
Promotor
Coding exon Intron Coding exon
D Gene duplication/deletion
*
C cis-regulatory mutation
*
*
trans-factor
B trans-regulatory mutation*
Target site
* A Protein-coding mutation
Deletion
*
*
miRNA
Current Biology
Figure 1. A diversity of mutations can cause changes in gene expression.
A schematic of gene structure showing: protein-coding exons (blue); 30 untranslated
region with miRNA target site (orange); cis-regulatory elements, such as enhancers
(green) and a promotor (arrow). Trans-acting factors, such as transcription factors
(yellow) and miRNAs (orange), are shown. Possible mutations include single-nucleotide
changes (red asterisk), deletions (white box) and whole-gene duplications. Changes in
gene regulation fall into four main categories: (A) Changes in amino-acid sequences.
These can change expression of the protein itself. This has been shown for both
nonsynonymous mutations (for example [13]) and deletions (for example, deletion of
a sequence motif can change the localization of the gene product [14]). (B) Trans-
regulatory mutations. Mutations in ‘regulatory proteins’, such as transcription factors,
can cause cascading effects on gene expression downstream in the pathway. (Some
transcription factors are known to evolve rapidly in the human lineage [15].) Mutations
in miRNAs, short, single-stranded RNAs, may have similar regulatory effects [16].
(C) Cis-regulatory mutations. We know that about 98.5% of our genome is non-coding,
but mutations in these regions, including silent substitutions in exons [17], can change
expression patterns. Most research has focused on changes in cis-regulatory elements
of genes (promotors and enhancers) as primary sources of variation in gene expression
[1]. But evolution may bemore opportunistic: recent work has suggested that mutations
in miRNA target sites can also alter protein expression [16,18]. (D) Gene duplication. Al-
though per-gene-duplication rates are low, these rates become appreciable when we
consider the entire genome [19]. Duplications can potentially play an important role in
gene regulation by increasing the amount of protein produced, a change that can have
important fitness consequences (for example, duplication of an esterase gene in aphids
confers resistance to insecticide [20]).but diets also vary among human
populations, as does the amount
of starch we consume. Perry et al.
[7] found that variation among
human populations in the number
of copies of the human salivary
amylase gene (AMY1) is
correlated with starch
consumption. Amylase is an
enzyme that breaks down starch tosimple sugars in our mouths.
Testing undergraduates
at Arizona State University, Perry
et al. [7] first found that the amount
of salivary amylase was highly
correlated with gene copy
number — the more gene copies,
the more protein. They then
extended their study to seven
human groups characterized by
Current Biology Vol 17 No 23
R1016either ‘high-starch’ diets
(populations depending on
agriculture: Japanese, Hadza, and
European Americans) or ‘low
starch’ diets (hunter-gather or
pastoral populations: Biaki,
Matubit, Datag, and Yakut). The
two groups showed a significant
difference in mean number of
amylase copies in the expected
direction (6.7 versus 5.4,
respectively). It is clear that copy
number has increased in the
human lineage as compared to our
more frugivorous cousins (chimps
have only one copy), but it is not
yet known whether differences
among human populations reflect
the gain or loss of ancestral
human gene copies. In one
comparison, that of Japanese to
Yakut populations, positive
selection may have increased
copy number: relative to other
genes having multiple copies,
AMY1 has duplicated much
faster.
What type of selection could
have acted here? Perry et al. [7]
suggest that copy number rose in
the starch-eating populations, and
did so for two reasons: a general
increase in fitness due to greater
efficiency of starch digestion, and
greater oral digestion of starch
that could provide nutrients
during episodes of diarrhea,
a historically significant cause of
human mortality. This hypothesis
is difficult to test directly because
we are unable to do controlled
crosses, in vivo studies, or
transgenics in humans. But DNA
sequencing of the multiple AMY1
copies could answer several
critical questions. Is the pattern
of nucleotide variation among
homologous gene copies
consistent with the action of
natural selection? Were the
duplication events coincident with
changes in foraging behavior
and/or the consumption of
domesticated grains? And did
increases in copy number occur
independently in these (and other)
high-starch populations, or did
gene flow distribute new copies
widely?
Compared to single nucleotide
changes in individual genes or the
regulatory elements that control
them, the loss and duplication of
genes has been less appreciatedas a source of adaptive novelty in
humans. Yet differences in the
number (or presence) of gene
copies between even closely
related species are striking: at
least 6.4% of genes in the human
genome are not found in
chimpanzees [9]. Moreover,
humans show substantial
polymorphism in gene copy
number [10].
The amylase results follow a
related study on the genetics of
human dietary differences. In
2006, Tishkoff and colleagues [11]
identified a mutation in the
upstream regulatory region of the
gene for lactase, an enzyme
important for digesting milk, in
pastoral African populations. Using
an in vitro system, they showed
that this mutation could increase
gene expression. The relevant
mutation, however, is not
a duplication, but probably
a change in cis-regulation. (An
independent cis-regulatory
mutation at this locus, also
conferring lactose tolerance, was
identified earlier in European
populations [12].)
Even in the simplest cases of
adaptation, then — increased
enzyme production to handle
new diets — evolution works in
multiple ways. Obviously, no
amount of a priori speculation will
tell us which sorts of mutations
will be important; the answer,
unfortunately, requires meticulous,
case-by-case analysis of putative
adaptations.
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1Department of Ecology and Evolution,
The University of Chicago, 1102 E. 57
St., Chicago, Illinois 60637, USA.
2Department of Organismic and
Evolutionary Biology, Museum of
Comparative Zoology, Harvard
University, 26 Oxford Street, Cambridge,
Massachusetts 02138, USA.
E-mail: j-coyne@uchicago.edu,
hoekstra@oeb.harvard.edu
DOI: 10.1016/j.cub.2007.10.009


Evolution of Protein Expression: New Genes for a New Diet 

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Evolution of Protein Expression: New Genes for a New Diet

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