Diet shapes the human genome

Summaries of newsworthy papers include Adding a pinch of sugar, Watching protein-cutting enzymes in action, Muscle metabolism and human evolution, The political brain, Dialling up damage responders and Stem cells have nervous impulses


For papers that will be published online on 09 September 2007

This press release is copyrighted to the Nature journals mentioned below.

This press release contains:

· Summaries of newsworthy papers:

Adding a pinch of sugar – Nature Chemical Biology

Watching protein-cutting enzymes in action – Nature Chemical Biology

Diet shapes the human genome – Nature Genetics

Muscle metabolism and human evolution – Nature Genetics

The political brain – Nature Neuroscience

Dialling up damage responders – Nature Immunology

Stem cells have nervous impulses – Nature Immunology

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

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*************************************NATURE CHEMICAL BIOLOGY ***********************************


[1] Adding a pinch of sugar

DOI: 10.1038/nchembio.2007.28

Enzymes can be engineered to decorate small molecules with a wide variety of sugars, according to a paper in the October issue of Nature Chemical Biology. The biological activity of many natural products—small molecules that occur naturally and form the basis for many drugs—is influenced by the addition of a sugar molecule. Thus, varying these sugar molecules can be important when looking for new drug leads; however, altering these sugars can be challenging using glycosyltransferases (enzymes that transfer sugars) because they typically only function with a narrow range of sugars and small molecules.

Jon Thorson and colleagues used a process called directed evolution, in which random mutations are introduced at select positions in an enzyme and a large number of mutated enzymes are screened for the desired activity. They were able to engineer a glycosyltransferase that can transfer a wide range of sugar molecules onto a variety of therapeutically important small molecules. These ‘mutant’ enzymes can now be used in the search for new therapeutics.

Author contact:

Jon Thorson (University of Wisconsin, Madison, WI, USA)

Tel: +1 608 262 3829; E-mail: [email protected]

[2] Watching protein-cutting enzymes in action

DOI: 10.1038/nchembio.2007.26

The activity of proteases – enzymes that cut other proteins and are important in diseases such as AIDS and cancer - can be imaged in living animals with ‘smart probes’ using a method reported in the October issue of Nature Chemical Biology. Cathepsin proteases are specific protein-cleaving enzymes involved in tumour formation and metastasis, and are important targets for diagnosing and treating cancer.

Using probes that only fluoresce when they react with active proteases, Matthew Bogyo and colleagues have imaged cathepsin activity in the tumours of living mice. Because the probes form a covalent bond (a permanent connection) with cathepsin, in vitro experiments can directly follow in vivo imaging to provide a mechanistic explanation for what is observed. The authors demonstrate that these probes are useful for testing the effectiveness of potential drugs.

Author contact:

Matthew Bogyo (Stanford University, Stanford, CA, USA)

Tel: +1 650 725 4132; E-mail: [email protected]

***********************************************NATURE GENETICS **************************************


[3] Diet shapes the human genome

DOI: 10.1038/ng2123

Human populations that have high starch diets have an increase in the number of copies of a gene whose product breaks down starch, reports a study to be published online this week in Nature Genetics. Although copy number variation has attracted a lot of recent attention, this is one of the first documented examples of positive selection on gene copy number in humans.

Starch has become a prominent component of the human diet. It is metabolized in part by salivary amylase, and the gene encoding it, AMY1, shows extensive variation in copy number. George Perry and colleagues estimated AMY1 copy number in 50 European Americans and showed that the levels of salivary amylase protein are positively correlated with gene copy number. They went on to show that individuals from three populations with high-starch diets tend to have more copies of AMY1 than individuals from populations with low-starch diets. Finally, the authors compared the extent of variation across the genome between two Asian populations – Japanese (high-starch diet) and Yakut pastoralists (low-starch diet) – and found that variation at AMY1 exceeds that of more than 97% of the other sites in the genome that were assessed.

The authors conclude from this that natural selection favored increased AMY1 copy number in at least some populations with high-starch diets. Interestingly, humans have significantly more copies of AMY1 than chimpanzees, which ingest relatively little starch. Increased AMY1 expression would probably improve the digestion of starchy foods, and possibly maintain energy absorption in the face of intestinal disease.

Author contact:

Nathaniel Dominy (University of California, Santa Cruz, CA, USA)

Tel: +1 831 459 2541; E-mail: [email protected]

[4] Muscle metabolism and human evolution

DOI: 10.1038/ng2122

A variant of a gene associated with elite athletic performance has been subject to strong, recent positive selection in humans, according to a study published online this week in Nature Genetics. Experiments on mice suggest that this variant may promote more efficient muscle metabolism.

The gene ACTN3, encoding alpha-actinin-3, is specifically expressed in the fast-twitch muscle fibers that are responsible for generating force at high velocity. ACTN3 exists in a non-functional truncated form in more than a billion people worldwide, and is overrepresented in endurance athletes. By contrast, the functional form is overrepresented in elite sprinters. Kathryn North and colleagues examined the extent of genetic variation in the vicinity of ACTN3 in individuals with the truncated version. They found very little variation, which is consistent with the truncated version of the gene being under positive selection.

To understand better the effect of the truncation on muscle function, the authors generated a line of mice lacking ACTN3, and found that there is a shift in muscle metabolism toward the more efficient aerobic pathway. These mice were also able to run on average 33% further before reaching exhaustion than mice with normal ACTN3 function. The authors conclude that this increased metabolic efficiency could explain the overrepresentation of the truncated form of ACTN3 in endurance athletes.

Author contact:

Kathryn North (Children’s Hospital at Westmead, Sydney, Australia)

Tel: +61 2 9845 3011; E-mail: [email protected]

Other papers from Nature Genetics to be published online at the same time and with the same embargo:

[5] Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than Europeans

DOI: 10.1038/ng2116

[6] The spindle checkpoint rescues the meiotic segregation of chromosomes whose crossovers are far from the centromere

DOI: 10.1038/ng2120

*******************************************NATURE NEUROSCIENCE ***********************************


[7] The political brain

DOI: 10.1038/nn1979

People with a more liberal outlook may have a greater sensitivity to cues signalling the need to change a habitual response, suggests an article online in Nature Neuroscience this week. The study shows that self-rated liberalism is associated with a type of brain activity involved in regulating conflict between a habitual tendency and an alternative response.

Previous psychological work found that, on average, conservatives tend to be more persistent in their judgements and decision-making, while liberals are more likely to be open to new experiences. These differences are related to a process known as conflict monitoring, a mechanism for detecting when a habitual response is not appropriate for a new situation.

David Amodio and colleagues recorded electrical activity from the brain using electroencephalograms (EEGs) in people who rated themselves as either conservative or liberal. During these recordings, subjects had to quickly press a button when they saw a cue, which was presented often enough that the button-press became habitual. However, subjects occasionally saw another, infrequent cue signalling them to withhold their habitual button press. When such response inhibition was required, liberals had significantly greater neural activity originating in the anterior cingulate cortex – known to be involved in conflict monitoring. Liberals were also more successful at withholding their habitual response when they saw the infrequent cue. The findings support previous suggestions that political orientation may in part reflect differences in cognitive mechanisms.

Author contact:

David Amodio, (New York University, NY, USA)
Tel: +1 212 998 3875; E-mail: [email protected]

Other papers from Nature Neuroscience to be published online at the same time and with the same embargo:

[8] Sensors for impossible stimuli may solve the stereo correspondence problem
DOI: 10.1038/nn1951

[9] COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas
DOI: 10.1038/nn1958

[10] Different roles of ribbon-associated and ribbon-free active zones in retinal bipolar cells
DOI: 10.1038/nn1963

[11] Auditory sensitivity regulation via rapid changes in expression of surface AMPA receptors
DOI: 10.1038/nn1974

[12] Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity
DOI: 10.1038/nn1977

*******************************************NATURE IMMUNOLOGY ************************************


[13] Dialling up damage responders

DOI: 10.1038/ni1508

Certain cells of the immune system more readily tolerate damage to their genes than other cells, up to a point. New research in Nature Immunology shows the protein BCL6, expressed in antibody-producing B cells, senses how much DNA damage is occurring inside these cells and activates repair pathways when damage becomes excessive.

BCL6 is a repressor that blocks expression of DNA repair enzymes in the presence of small amounts of damage. This suppression is beneficial to the B cells as these cells can ‘fine-tune’ their antibody responses by mutating the antibody genes or undergoing what is called ‘class switch recombination’, a genetic rearrangement that allows different types of antibodies to be produced.

Riccardo Dalla-Favera and colleagues show excessive DNA damage in these B cells can be recognized by BCL6. BCL6 acts as a ‘damage-sensitive’ resistor that, once tipped beyond a threshold amount of accumulated DNA breaks, initiates a pathway that leads to its own destruction and turns on repair enzymes. These findings further our understanding of BCL6, which is commonly found to be mutated in forms of B cell cancers, and may thereby be instructive in designing therapies to blunt BCL6 activity in these cancers.

Author contact:

Riccardo Dalla-Favera (Columbia University, New York, NY, USA)

Tel: +1 212 851 5273; E-mail: [email protected]

[14] Stem cells have nervous impulses

DOI: 10.1038/ni1509

Blood stem cells become activated in response to signals released by nerve cells according to research published online this week in Nature Immunology.

Tsvee Lapidot and colleagues report bone marrow stem cells express dopamine receptors. Release of neurotransmitters, as occurs during times of stress, triggers the blood cells to divide and migrate from their protected bone marrow environment. Treatment of mice with dopamine or other neurotransmitters led to increased numbers of these stem cells in bone marrow and in the blood circulation. Neurotransmitter stimulation of human bone marrow cells likewise increased their engraftment potential upon transplantation into ‘humanized mouse’ recipients, whose immune system is reconstituted by the human cells. Such findings might translate to increased efficiency of therapies that require bone marrow transplantation.

Author contact:

Tsvee Lapidot (Weizmann Institute of Science, Rehovot, Israel)

Tel: +972 8 934 2481; E-mail: [email protected]

Other papers from Nature Immunology to be published online at the same time and with the same embargo:

[15] Germline-encoded recognition of diverse glycolipids by natural killer T cells

DOI: 10.1038/ni1510


Items from other Nature journals to be published online at the same time and with the same embargo:

Nature PHYSICS (

[16] Incoherent non-Fermi-liquid scattering in a Kondo lattice

DOI: 10.1038/nphys711

[17] A new method for generating ultraintense and ultrashort laser pulses

DOI: 10.1038/nphys717


[18] Substrate-induced bandgap opening in epitaxial graphene

DOI: 10.1038/nmat2003

[19] A new multifunctional 3.5 V iron-based phosphate cathode for rechargeable batteries

DOI: 10.1038/nmat2007


[20] Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche

DOI: 10.1038/nm1630

[21] Protein carbamylation links inflammation, smoking, uremia and atherogenesis

DOI: 10.1038/nm1637

[22] Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation

DOI: 10.1038/nm1651


[23] Motor-free mitochondrial presequence translocase drives membrane integration of preproteins

DOI: 10.1038/ncb1635

[24] Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum

DOI: 10.1038/ncb1636

[25] A proteomic screen reveals SCFGrr1 targets that regulate the glycolytic–gluconeogenic switch

DOI: 10.1038/ncb1639

[26] Polycomb response elements mediate the formation of chromosome higher-order structures in the bithorax complex

DOI: 10.1038/ncb1637


[27] Distinct domains of complexin I differentially regulate neurotransmitter release

DOI: 10.1038/nsmb1292

[28] Structure-function relationship of CAP-Gly domains

DOI: 10.1038/nsmb1291

[29] CLIP-170 autoinhibition mimics intermolecular interactions with p150glued or EB1

DOI: 10.1038/nsmb1299


[30] Three-dimensional preparation and imaging reveal intrinsic microtubule properties

DOI: 10.1038/nmeth1087

[31] A probability-based approach for the analysis of large-scale RNAi screens

DOI: 10.1038/nmeth1089



The following list of places refers to the whereabouts of authors on the papers numbered in this release. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

Canberra: 4
Clayton: 15
Parkville: 15
Sydney: 4

Edmonton: 22
Montreal: 22

Toronto: 29

Waterloo: 19


Oulu: 21


Gif-sur-Yvette: 23

Montpellier: 26


Freiburg: 23

Goettingen: 27

Heidelberg: 30

Hilden: 31


Jerusalem: 14

Rehovot: 14

Tel-Hashomer: 14

Tsrifin: 14

Naples: 9, 26

Turin: 9


Hyogo: 10

Tokyo: 10


Rotterdam: 28


Madrid: 18


Uppsala: 23


Villigen: 28

Zurich: 22, 28


Cambridge: 3

Newcastle upon Tyne: 8



Tempe: 3


Berkeley: 12, 18

La Jolla: 9, 16, 21, 24, 31

Los Angeles: 7, 20

San Diego: 21, 31

San Francisco: 25

Santa Cruz: 3, 18

Stanford: 2, 3


Denver: 15


Atlanta: 18


Baltimore: 20

Bethesda: 5, 8, 20


Boston: 3, 5, 11, 13, 18

Cambridge: 6

Worcester: 26

New York

New York: 7, 13

North Carolina

Durham: 10, 13


Cleveland: 21


Portland: 10


Dallas: 27

Houston: 27


Madison: 1


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Fabio Pulizzi

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Published: 09 Sep 2007

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