PERSPECTIVES
Prosser et al. propose that X-ROS signaling regulates Ca2+ signaling in the heart undernormal conditions; in contrast, it may trigger abnormal rhythms in an injured or diseased heart. Afuture challenge will be to test
whether the changes they observed in isolatedheart cells also occur in the beating heart.
References and Notes
1. R. Knöll et al., J. Mol. Med. (Berl.) 81, 750 (2003).
2. B. L. Prosser et al., Science 333, 1440 (2011).

3. I. A. Williams, D. G. Allen, Am. J. Physiol. Heart Circ.
Physiol. 293, H1969 (2007).
4. M. G. Petroff et al., Nat. Cell Biol. 3, 867 (2001).
5. G. Iribe, P. Kohl, Prog. Biophys. Mol. Biol. 97, 298 (2008).
6. G. Iribe et al., Circ. Res. 104, 787 (2009).
7. N. D. Ullrich, M. Fanchaouy, K. Gusev, N. Shirokova, E. Niggli, Am. J. Physiol. Heart Circ. Physiol. 297, H1992 (2009).
8. D. M. Bers, Nature 415, 198 (2002).
9. G. Meissner, Curr. Top Membr 66, 91 (2010).
10. S. Györke, D. Terentyev, Cardiovasc. Res. 77, 245 (2008).
11. B. L. Prosser et al. J. Gen. Physiol. 136, 135 (2010).
12. J. J. Marengo, C. Hidalgo, R. Bull, Biophys. J. 74, 1263
(1998).

13. G. Sánchez, Z. Pedrozo, R. J. Domenech, C. Hidalgo,
P. Donoso, J. Mol. Cell. Cardiol. 39, 982 (2005).
14. G. Sánchez et al., Cardiovasc. Res. 77, 380(2008).
15. C. I. Caldiz et al., J. Physiol. 584, 895 (2007).
16. H. E. Cingolani, I. L. Ennis, E. A. Aiello, N. G. Pérez,Pflugers Arch. 462, 29 (2011).
17. Research was supported by FONDECYT-FONDAP(grants 1501006 and BNI P-09-015F) and FONDECYT(grant 1110257).

10.1126/science.1212183

EVOLUTION

Mother Tongue and Y Chromosomes

A global picture is emerging of sex-specifictransmission of language change in quite
different regions and continents.

Peter Forster1,2 and Colin Renfrew3

Murray Edwards College, University of Cambridge, Cambridge CB3 0DF, UK. 2Institute of Forensic Genetics, 48161
Münster, Germany. 3McDonald Institute for ArchaeologicalResearch, University of Cambridge, Cambridge CB2 3ER, UK.
E-mail: pf223@cam.ac.uk

1390

graphy in Bantu-speaking areas.
Sex-specific transmission of languagechange may be a feature when the mechanismof change is by farming/language dispersal(6). This dispersal hypothesis describes how
language change can be linked to the early
spread of food—domesticated animals andplants—by farmers speaking a protolanguage.
In the Americas, language replacement in thecourse of postulated farming dispersal has
been found to correlate in the Uto-Aztecan
language family with Y-chromosomal DNA
variation but not with mtDNA variation (7).
As for the immigrant Indo-European andthe presumably indigenous Dravidian languages in India, there is one major candidate genetic marker for immigration fromthe northwest. It is a Y-chromosome DNA

Icelandic

Tibeto-Burman
Indo-European

Uto-Aztecan
Niger-Congo

Austroasiatic
Malayo-PolynesianDravidian“Melanesian”
Bantu

Language transmission. Glossogenetic studies relate Y-chromosome DNA types with language in the indicated regions. Such correlation is not observed for mtDNA, which is inherited from the mother. “Melanesian”
designates non–Malayo-Polynesian languages in New Guinea, where Malayo-Polynesian is spoken in coastal
pockets. The hatched region shows Bantu as a branch within the Niger-Congo language family.

9 SEPTEMBER 2011 VOL 333 SCIENCE www.sciencemag.org
Published by AAASCREDIT: B. STRAUCH/SCIENCE

1

who noted that in East Asia, a patrilocal residence pattern (where women rather thanmen change residence upon marriage) favors
geographic stability of the male lineage. This
may reflect the migration of men and women(and their language) to an already populatedarea, but once settled, the women intermarrywith men from neighboring populations andmove to their villages. In this scenario, theimmigrant men remain, and the language
therefore stays in the same place as theimmigrant Y chromosomes. And in Africa,
Wood et al. (4) and de Filippo et al. (5) foundthat Bantu and other Niger-Congo languages
correlate well with Y-chromosome types(indicating male lineages), whereas mtDNAtypes (associated with maternal descent)correlate not with language but with geo-

Downloaded from http://science.sciencemag.org/ on December 12, 2020S

ome 6000 different languages are spoken in the world today, and tracing theprehistory of languages and of language change by means of genetic markers
has long been a goal (1). However, this has
proven to be a more challenging task thansimply tracing colonizations. Nevertheless, anumber of genetic studies over the past few
years have started to address language andlanguage change before recorded history.
A correlation is emerging that suggests language change in an already-populated region
may require a minimum proportion of immigrant males, as reflected in Y-chromosome
DNA types. By contrast, the female lineages,
as indicated by mitochondrial DNA (mtDNA)
types, do not reflect the survivor language butrepresent more ancient settlement.
Chaubey et al. have found that in theIndian subcontinent, the Austroasiatic languages spoken by tribes such as the Munda
show a high proportion (75%) of immigrantY-chromosome DNA (a type called O2),
which is generally found among peoples ofEast Asia, but predominantly (75 to 100%)
local Indian mtDNA types (2) (in humans,
mtDNA is inherited from the mother) (seethe figure). Similarly, the study found that
another major language family, Tibeto-Burman in northeastern India, coincides witha high proportion of immigrant East Asian
Y-chromosome O3 types, which are generally found in populations of southeastern Asia. The East Asian mtDNA is rarer in
Tibeto-Burman speakers residing in India.
A compatible observation has recently
been made by Stoneking and Delfin (3),PERSPECTIVES
colonization of Iceland from 874 C.E. by
Scandinavian Vikings and abducted womenfrom the British Isles (10, 11). Icelandic
mtDNA today is mainly British, while the Y
chromosome is predominantly Scandinavian,as indeed is the Icelandic language. A contrasting case is found in Greenland, whereboth the mtDNA (12) and the language today
are nearly pure Eskimo, while half the Y chromosomes are European (13), evidently fromcontact with male European whalers over thecenturies. The Greenlandic and Dravidian
cases suggest that a Y-chromosomal signal
may be a necessary factor, but not a sufficient
one, as a predictor of language.
If the emerging correlation is confirmed,
there should be underlying causal factors ofa social nature. It may be that during colonization episodes by emigrating agriculturalists, men generally outnumbered women in
the pioneer colonizing groups and took wives
from the local community. When the parents
have different linguistic backgrounds, it may
often be the language of the father that is
dominant within the family group. It is also
relevant that men have a substantially morevariable number of offspring than do women,
as has been recorded both in prehistoric tribes
such as the 19th- and 20th-century Polar

Eskimo from Greenland (14) and in historic
figures such as Genghis Khan (1162 to 1227
C.E.), whose Y chromosome is presumed
to be widespread across his former Mongol
empire and is carried by 0.5% of the world’s
male population today (15). Prehistoric
women may more readily have adopted thelanguage of immigrant males, particularly ifthese newcomers brought with them militaryprowess or a perceived higher status associated with farming or metalworking.
References
1. L. L. Cavalli-Sforza et al., Proc. Natl. Acad. Sci. U.S.A. 85,6002 (1988).
2. G. Chaubey et al., Mol. Biol. Evol. 28, 1013 (2011).
3. M. Stoneking, F. Delfin, Curr. Biol. 20, R188 (2010).
4. E. T. Wood et al., Eur. J. Hum. Genet. 13, 867 (2005).
5. C. de Filippo et al., Mol. Biol. Evol. 28, 1255 (2011).
6. P. Bellwood, C. Renfrew, Examining the Farming/
Language Dispersal Hypothesis (McDonald Institute,Cambridge, 2002).
7. B. M. Kemp et al., Proc. Natl. Acad. Sci. U.S.A. 107,6759 (2010).
8. S. Sengupta et al., Am. J. Hum. Genet. 78, 202 (2006).
9. M. Kayser et al., Mol. Biol. Evol. 25, 1362 (2008).
10. A. Helgason et al., Am. J. Hum. Genet. 68, 723 (2001).
11. P. Forster et al., in Traces of Ancestry, M. Jones, Ed.
(McDonald Institute, Cambridge, 2004), pp. 99–111.
12. J. Saillard et al., Am. J. Hum. Genet. 67, 718 (2000).
13. E. Bosch et al., Hum. Genet. 112, 353 (2003).
14. S. Matsumura, P. Forster, Proc. Biol. Sci. 275, 1501 (2008).
15. T. Zerjal et al., Am. J. Hum. Genet. 72, 717 (2003).
10.1126/science.1205331

NEUROSCIENCE

How Many Cell Types DoesIt Take to Wire a Brain?

Microglia play an important role inthe maturation of synaptic circuits
in newborn mice.

Richard M. Ransohoff1 and Beth Stevens2

M

icroglia, highly mobile immune
cells that reside in the central nervous system, are traditionallyviewed as “barometers” of the brain because
they rapidly respond to cellular damage
caused by injury and disease by engulfing
and cleaning up debris (1). Imaging studies,
however, have revealed that microglia are alsoceaselessly active in healthy brains, and otherstudies have shown that this activity is often
associated with synapses, which move signals
between neurons (2–4). Despite these intriguing observations, the function of microglia athealthy synapses has been elusive. On page
1456 of this issue, Paolicelli et al. (5) help pin
it down. They demonstrate that microglia are
1

Neuroinflammation Research Center, Lerner ResearchInstitute, Cleveland Clinic, Cleveland, OH 44195, USA.
2
Department of Neurology, Children’s Hospital, Harvard
Medical School, Boston, MA 02115, USA. E-mail: ransohr@ccf.org; beth.stevens@childrens.harvard.edu

involved in the development of brain wiring in
newborn mice and that disrupting microgliasynapse interactions delays the maturation ofsynaptic circuits. The finding offers insight
into the mechanisms underlying synapse maturation and into brain diseases in which synaptic connectivity is altered.
In the brain, microglia are the only
cells that express the fractalkine receptor
CX3CR1; it specifically binds the chemokine
fractalkine CX3CL1, which is expressed byneurons (6). Fractalkine signaling often modulates the activation of microglia response to
injury or disease (7, 8). In genetically modified knockout (KO) mice unable to produce
the fractalkine receptor (Cx3cr1KO), there isa transient decrease in microglial density inseveral developing brain regions, including
the hippocampus, a region critical for learning and memory. To determine whether thisdecrease affects the development of hippo-campal synapses, the researchers comparedCx3cr1KO mice with age-matched controls,
looking for anatomical, electrophysiological,and behavioral abnormalities associated withdisrupted synaptic maturation.
They observed that newborn Cx3cr1KO
mice had an increased density of hippocampal spines, small protrusions from a neuron’sdendrite that receives synaptic input frompresynaptic axons. This observation is consistent with a role for microglia in “pruning”
of unneeded spines in normal mice during
brain development. Indeed, the researchers
observed postsynaptic-density (PSD) immunoreactivity within microglia cytoplasm,suggesting that microglia engulf and remove
spines during this period of synaptic remodeling. In addition, electrophysiological andbehavioral experiments demonstrated adelay in the maturation of hippocampal synapses in the KO mice. For example, elec-

www.sciencemag.org SCIENCE VOL 333 9 SEPTEMBER 2011
Published by AAAS

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type (J2a) rather than an mtDNA type, andits immigrant status is suggested by its presence at 10 to 20% frequency in high castes,
both in Indo-European speakers and farther
south among Dravidian speakers, and its
near-absence in lower castes or “tribals” (8).
Perhaps the most striking example of sexbiased language change comes from a genetic
study on the prehistoric encounter of expanding Malayo-Polynesians with resident Melanesians in New Guinea and the neighboring
Admiralty Islands (9). The New Guineancoast contains pockets of Malayo-Polynesian–speaking areas separated by Melanesianareas. The presence of Malayo-Polynesian
mtDNA (at local frequencies of 40 to 50%) issimilar in these areas regardless of language,
whereas the Malayo-Polynesian Y chromosome correlates strongly with the presenceof Malayo-Polynesian languages. Mirroring
the situation in the Indian upper castes, thepresence of immigrant Malayo-PolynesianY-chromosome DNA is modest, at frequencies of 10 to 20%, in the Malayo-Polynesian
pockets, but this figure is still an order ofmagnitude higher than in the non–MalayoPolynesian areas.
In Europe, a genetically researched protohistoric case of language dominance is the1391