RESEARCH NEWS & VIEWS

Claudio Franco and Holger Gerhardt

are at the Vascular Biology Laboratory,
London Research Institute, Cancer Research
UK, Lincolns Inn Fields Laboratories,
London WC2A 3LY, UK. H.G. is also at
the Vascular Patterning Laboratory,

Vesalius Research Center, Leuven, Belgium.

e-mail: holger.gerhardt@cancer.org.uk
1. Carmeliet, P. Nature 438, 932936 (2005).
2. Zheng, Y. et al. Proc. Natl Acad. Sci. USA 109,
93429347 (2012).
3. van der Meer, A. D., Poot, A. A., Duits, M. H., Feijen, J.

& Vermes, I. J. Biomed. Biotechnol. 2009,

82318248 (2009).
4. Potente, M., Gerhardt, H. & Carmeliet, P. Cell 146,
873887 (2011).
5. Price, G. M. et al. Biomaterials 31, 61826189
(2010).
6. Tsai, M. et al. J. Clin. Invest. 122, 408418 (2012).

PL A N T N U TR I T I ON

Rooting for more

phosphorus
The identification of an enzyme in rice that confers improved plant yields on
phosphorus-deficient soils could open up new avenues for generating nutrientefficient crops that can thrive on marginally fertile soils. See Letter p.535
L E O N V. K O C H I A N

hosphorus is probably the most limiting

mineral nutrient for plants. Many of our
planets soils are low in the mineral, and
this includes approximately half of the worlds
agricultural lands1. Hence, there is considerable interest in developing plant varieties that
are more phosphorus efficient that is, crops
that can produce higher yields while using less
soil phosphorus. On page 535 of this issue,
Gamuyao et al.2 report the identification of
the first phosphorus-efficiency gene in plants.
The gene encodes a protein kinase enzyme that
significantly enhances grain yield from rice
plants grown on phosphorus-deficient soils.
Multiple factors contribute to the phosphorus
problem. A large fraction of soil phosphorus is held very tightly to the surface of soil

particles or is tied up (fixed) as organic phosphorus compounds, and is therefore relatively

unavailable for plant uptake (Fig.1). Furthermore, many low-phosphorus regions are in
developing countries, where soils are often
degraded and where many farmers lack the
financial resources to purchase phosphorus
fertilizers. Thus, plant access to the mineral
plays a part in the precarious food-security
situation in some of these regions. To further
exacerbate the problem, the phosphorus used
in fertilizers is obtained from rock phosphate,
which is a non-renewable resource that could
be depleted in 50100years3. Even for the highinput agriculture common in developed countries, much of the fertilizer-derived phosphorus
either becomes fixed (and therefore unavailable to plants) or is lost through leaching into
ground and surface waters, which is damaging
US DEPARTMENT OF AGRICULTURE

These simple results, although preliminary,

highlight the potential for microfluidic devices
to improve our knowledge of fundamental
aspects of blood-vessel physiology.
However, the remodelling of the microvascular network demonstrated by Zheng
et al. is still rudimentary, and does not fulfil
all of the requirements for the replacement
of in vivo models. Sprouting in their system,
and the additional remodelling of the vascular structures that occurs afterwards, remain
unsatisfactory, and improvements in culture
conditions will be required to emulate the
dynamic complexity seen in vivo. Yet the
authors report demonstrates the possibility of creating an open and flexible assay in
which blood, plasma or culture medium
flows through vessels that can be stimulated
and manipulated, and that allows real-time
observation of the dynamics of endothelialcell behaviour through the different phases
of angiogenesis. We envisage that improved
versions of Zheng and colleagues device will
permit quick and accurate manipulation of
plasma flow and composition, as well as the
delivery of experimental molecules to screen
their effects on endothelial function.
Today, the full pattern of vascular remodelling is still beyond the reach of existing
microfluidic devices. Moreover, achieving an
adequate flow in complex vascular networks in
vitro remains problematic; most current systems rely on gravity-driven flow, which provides insufficient shear forces to mimic in vivo
conditions. Looking ahead, from an experimentalists point of view, the ideal microfluidic
device should mimic conditions in living
organisms and be easy to assemble. It should
also enable the tight control and manipulation
of all parameters relevant to angiogenesis, be
scalable to high-throughput analysis, and
facilitate the application of standard methods
of molecular analysis and live imaging.
Developments such as the one reported by
Zheng and colleagues are closing the technological gaps, and we foresee a strengthening
of microfluidic devices as platforms to investigate blood-vessel function and the interaction
of blood vessels with tumours. Moreover, the
establishment of a functional, hierarchically
branched vascular network in vitro that could
support the formation of new tissues from
stem cells would be an extraordinary achievement that would boost the field of tissue
engineering. Time will tell whether the vessel
remodelling observed in the authors microfluidic chamber can be driven far enough to
develop systems conducive to large-scale tissue
engineering for transplantation.

Phosphorus-retention potential
Low
Moderate

High
Very high

Other regions
Dry
Cold

Ice/glacier

Figure 1 | The problem of phosphorus. Many of the worlds agricultural soils are in regions of high
or very high phosphorus-retention potential, which means that the phosphorus is tightly bound to soil
particles or fixed in phosphorus-containing organic compounds. High phosphorus retention leads to
low availability of phosphorus for plants in these regions. Gamuyao et al.2 have identified a rice enzyme
that enhances grain yield from plants grown on phosphorus-deficient soils.

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2012 Macmillan Publishers Limited. All rights reserved

NEWS & VIEWS RESEARCH

to the surrounding environment.
A possible way to circumvent these problems
is to generate plant varieties that simply need
less of the nutrient. This particular episode in
that quest began around 15 years ago, when
researchers from the group presenting the
current paper began to study a subpopulation
of rice plants called the aus varieties, which
originated from nutrient-poor soils in India.
There was a growing awareness that these traditional rice varieties were likely to be a rich
source of genes encoding tolerance to abiotic
stresses, such as prolonged flooding4. A genetic
screen of multiple rice varieties led to the
identification5 of Kasalath, an aus line that is
significantly more phosphorus efficient than
the varieties currently used for rice production. A subsequent genetic analysis of plants
generated from a cross between Kasalath and
a modern, phosphorus-inefficient rice variety
determined that several regions of the rice
genome are associated with improved phosphorus efficiency5,6. The phosphorus uptake
(PUP) genomic region that has the largest
effect is located on rice chromosome 12 and
has been named Pup1 (ref.7).
However, subsequent efforts to identify
the specific gene, or genes, responsible for
phosphorus efficiency in the Kasalath strain
were complicated by the fact that greater
phosphorus efficiency can arise from several
aspects of plant physiology. For example, moreactive root growth that positions roots closer
to where the soil phosphorus is located, or
greater root-mediated biological and chemical activity to solubilize and absorb fixed
phosphorus can both lead to more efficient
acquisition. In addition, more-efficient cellular
use of the mineral can contribute to enhanced
phosphorus efficiency.
To try to tease apart which of these processes
are influenced by Pup1, the researchers used
breeding techniques to introduce the Pup1containing region into modern rice lines that
are phosphorus inefficient. The offspring lines
had significantly higher grain and biomass
yields than the parent lines when grown on
phosphorus-deficient soils, and physiological analysis showed that this resulted from
significantly greater phosphorus uptake and
accumulation8.
The research group subsequently compared9 the DNA sequence containing the
Pup1 region in the Kasalath variety with
the reference genome sequence for rice, which
was generated from the modern variety,
Nipponbare. The sequences differed considerably, with the Kasalath sequence containing
several putative genes not present in Nipponbare. Gene-expression analysis allowed
the authors to single out one of these inserted
genes, which encodes a protein kinase. This
gene is expressed at high levels in the roots of
plants harbouring the Kasalath Pup1 region,
and expression of the gene is further enhanced
in phosphorus-deficient conditions.

In the current paper2, Gamuyao and colleagues further characterize this gene, which
they have named PSTOL1, for phosphorusstarvation tolerance 1. The authors demonstrate that modern rice lines that are genetically
engineered to overexpress PSTOL1 show significant increases in grain and biomass production compared with wild-type plants when
the plants are grown on phosphorus-deficient
soils. They also show that the PSTOL1 protein
belongs to the receptor-like cytoplasmic kinase
sub-group of protein kinases. This is interesting, because receptor-like kinases have been
implicated in plant responses to several types
of abiotic stress, including drought10.
By comparing the root architecture of rice
plants overexpressing PSTOL1 with that of
the corresponding lines lacking the kinase,
the authors found that PSTOL1 expression
resulted in increased early root growth and
root proliferation, suggesting that the kinase
enhances the plants ability to mine soil phosphorus. The proposal that PSTOL1 functions
in root development and growth was supported
by studies showing that PSTOL1 expression is
confined to specific tissue regions where crown
roots, which make up a substantial portion of
the mature rice root system, begin to emerge.
These findings have opened up new avenues
for improving crop plant phosphorus efficiency and possibly the efficiency of the
uptake of other nutrients as well. Considerable work remains to be done to elucidate the
molecular mechanisms and downstream targets of PSTOL1. But the researchers are already
attempting to translate their discoveries into

improved phosphorus efficiency in rice crops

by use of targeted inter-variety breeding. It will
be interesting to see how stable this trait is in
plant varieties from different genetic backgrounds and in different growth environments.
In addition, the authors earlier genetic screens
identified other genomic regions associated
with enhanced phosphorus efficiency, and it
will be exciting to watch for the identification
of specific genes within these regions, and for
the discovery of potential synergistic effects on
plant-nutrient efficiency when these genes or
regions are combined. Finally, Gamuyao and
colleagues research has highlighted the value
that lies in investigating traditional plant varieties for beneficial traits that might have been
lost during domestication.
Leon V. Kochian is at the US Department
of Agricultures Robert W. Holley Center for
Agriculture and Health, and the Department
of Plant Biology, Cornell University, Ithaca,
New York 14853, USA.
e-mail: leon.kochian@ars.usda.gov
1. Lynch, J. P. Plant Physiol. 156, 10411049 (2011).
2. Gamuyao, R. et al. Nature 488, 535539 (2012).
3. Cordell, D., Drangert, J.-O. & White, S. Glob. Environ.
Change 19, 292305 (2009).
4. Xu, K. et al. Nature 442, 705708 (2006).
5. Wissuwa, M. & Ae, N. Plant Breed. 120, 4348
(2001).
6. Wissuwa, M., Yano, M. & Ae, N. Theor. Appl. Genet.
97, 777783 (1998).
7. Wissuwa, M., Wegner, J., Ae, N. & Yano, M. Theor.
Appl. Genet. 105, 890897 (2002).
8. Wissuwa, M. Plant Soil 269, 5768 (2005).
9. Heuer, S. et al. Plant Biotechnol. J. 7, 456471 (2009).
10. Marshall, A. et al. Plant Cell 24, 22622278 (2012).

GEN ETI C S

The rate of human

mutation
A comprehensive analysis of human spontaneous mutation has revealed a strong
influence of paternal age, suggesting a link between an increasing number of
older fathers and the rise in disorders such as autism. See Article p.471
ALEXEY KONDRASHOV

utations are common on the scale of

whole genomes, but rare on the scale
of individual nucleotides. So until
large-scale DNA sequencing became practical, measuring the rate at which novel mutations accumulate in a genome was a daunting
task. Now, however, de novo mutations can be
detected by a straightforward comparison of
parent and offspring genotypes, making obsolete several ingenious methods that were previously used for this purpose. Such comparisons
will rapidly produce reliable estimates of the

parameters of spontaneous mutation in many

species. On page 471 of this issue, Kong et al.1
report these figures for humans. They show
that a newborns genome sequence contains,
on average, 60 new small-scale mutations, and
that this number depends strongly on the age
of the father at the time of conception.
Kong and colleagues study is by far the
largest of its kind yet conducted, involving
78 Icelandic parentoffspring trios. Their estimate of 60 new mutations per generation is
in agreement with previous calculations2, but
their data also reveal that, although a 20-yearold father transmits, on average, approximately

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2012 Macmillan Publishers Limited. All rights reserved