Several recent studies suggestthat transcriptional rewiring similarto that seen in the catabolism ofgalactose in yeasts is a recurrentevolutionary theme observed ingenetic pathways across life’skingdoms [16]. Interestingly,several such rewirings — of themating circuit [17], of the ribosomaltranscriptional module [18], or ofthe mitochondrial ribosomal genes[19] — have been identified incomparisons between C. albicansand S. cerevisiae. The most strikingdifferences between the twoorganisms are the conditionsunder which they ferment.C. albicans — like mostyeasts — prefers to respire,whereas S. cerevisiae prefers toferment (even in the presence ofoxygen), an adaptation linked tothe whole-genome duplication andthe emergence of the fruit-bearingangiosperms [11,20]. Could muchof this rewiring have been triggeredby these extraordinary evolutionaryevents? Food for thought, at least,and hopefully an appetizer forcontinued research.

References1. Bell, G. (1997). The Basics of Selection

(Chapman & Hall).2. Rubio-Texeira, M. (2005). A comparative

analysis of the GAL genetic switchbetween not-so-distant cousins:Saccharomyces cerevisiae versusKluyveromyces lactis. FEMS Yeast Res. 5,1115–1128.

3. Hittinger, C.T., Rokas, A., and Carroll, S.B.(2004). Parallel inactivation of multiple

GAL pathway genes and ecologicaldiversification in yeasts. Proc. Natl. Acad.Sci. USA 101, 14144–14149.

4. Martchenko, M., Levitin, A., Hogues, H.,Nantel, A., and Whiteway, M. (2007).Transcriptional rewiring of fungalgalactose metabolism circuitry. Curr.Biol. 17, 1007–1013.

5. Johnston, M. (1987). A model fungal generegulatory mechanism: the GAL genes ofSaccharomyces cerevisiae. Microbiol.Rev. 51, 458–476.

6. Bhat, P.J., and Murthy, T.V. (2001).Transcriptional control of the GAL/MELregulon of yeast Saccharomycescerevisiae: mechanism of galactose-mediated signal transduction. Mol.Microbiol. 40, 1059–1066.

7. Peng, G., and Hopper, J.E. (2002). Geneactivation by interaction of an inhibitorwith a cytoplasmic signaling protein.Proc. Natl. Acad. Sci. USA 99,8548–8553.

8. Mortimer, R.K., Romano, P., Suzzi, G.,and Polsinelli, M. (1994). Genomerenewal: a new phenomenon revealedfrom a genetic study of 43 strains ofSaccharomyces cerevisiae derived fromnatural fermentation of grape musts.Yeast 10, 1543–1552.

9. Meyer, J., Walker-Jonah, A., andHollenberg, C.P. (1991). Galactokinaseencoded by GAL1 is a bifunctional proteinrequired for induction of the GAL genes inKluyveromyces lactis and is able tosuppress the gal3 phenotype inSaccharomyces cerevisiae. Mol. Cell Biol.11, 5454–5461.

10. Braun, B.R., van Het Hoog, M.,d’Enfert, C., Martchenko, M., Dungan, J.,Kuo, A., Inglis, D.O., Uhl, M.A.,Hogues, H., et al. (2005). A human-curatedannotation of the Candida albicansgenome. PLoS Genet. 1, 36–57.

11. Wolfe, K.H., and Shields, D.C. (1997).Molecular evidence for an ancientduplication of the entire yeast genome.Nature 387, 708–713.

12. Scannell, D.R., Frank, A.C., Conant, G.C.,Byrne, K.P., Woolfit, M., and Wolfe, K.H.(2007). Independent sorting-out ofthousands of duplicated gene pairs in twoyeast species descended from a whole-genome duplication. Proc. Natl. Acad. Sci.USA 104, 8397–8402.

13. van Het Hoog, M., Rast, T.J.,Martchenko, M., Grindle, S., Dignard, D.,Hogues, H., Cuomo, C., Berriman, M.,Scherer, S., Magee, B., et al. (2007).Assembly of the Candida albicansgenome into sixteen supercontigs alignedon the eight chromosomes. Genome Biol.8, R52.

14. Cliften, P.F., Fulton, R.S., Wilson, R.K.,and Johnston, M. (2006). After theduplication: gene loss and adaptation inSaccharomyces genomes. Genetics 172,863–872.

15. Johnston, M. (1999). Feasting, fasting andfermenting. Glucose sensing in yeast andother cells. Trends Genet. 15, 29–33.

16. Rokas, A. (2006). Evolution: differentpaths to the same end. Nature 443,401–402.

17. Tsong, A.E., Tuch, B.B., Li, H., andJohnson, A.D. (2006). Evolution ofalternate transcriptional circuits withidentical logic. Nature 443, 415–420.

18. Tanay, A., Regev, A., and Shamir, R.(2005). Conservation and evolvability inregulatory networks: the evolution ofribosomal regulation in yeast. Proc. Natl.Acad. Sci. USA 102, 7203–7208.

19. Ihmels, J., Bergmann, S., Gerami-Nejad, M., Yanai, I., McClellan, M.,Berman, J., and Barkai, N. (2005).Rewiring of the yeast transcriptionalnetwork through the evolution of motifusage. Science 309, 938–940.

20. Merico, A., Sulo, P., Piskur, J., andCompagno, C. (2007). Fermentativelifestyle in yeasts belonging to theSaccharomyces complex. FEBS J. 274,976–989.

1Vanderbilt University, Department ofBiological Sciences, VU Station B351634, Nashville, Tennessee 37235,USA. 2Washington University inSt. Louis, Center for Genome Sciences,School of Medicine, St. Louis, Missouri63108, USA.E-mail: antonis.rokas@vanderbilt.edu;cthittinger@genetics.wustl.edu

DOI: 10.1016/j.cub.2007.06.025

Current Biology Vol 17 No 16R628

Language Acquisition: When Doesthe Learning Begin?

Language acquisition is quite sophisticated by four months of age. Twocues that babies use to discriminate their language from another arethe stress patterns of words and visual cues inherent in languageproduction.

Susan J. Hespos

Benjamin Franklin is credited withthe invention of bifocal glasses,Franklin said he found themparticularly useful at dinner inFrance, where he could see thefood he was eating and watch thefacial expressions of those seatedat the table with him, which helped

interpret the words being said. Hewrote: ‘‘I understand French betterby the help of my Spectacles.’’Language is a multimodalexperience; we obtain linguisticinformation through hearing,seeing people’s lips move, readingand interpreting the context thatsurrounds the linguistic input. Itis an impressive accomplishment

that children synthesize all thisinput into meaningful ideas andthat they acquire language ina short amount of time with noformal training. Even moreastonishingly, every typicallydeveloping child manages toaccomplish this feat. The questionasked by parents and scientistsalike is: how do they do it?

Part of the answer is that thereappears to be a language-dedicated system from the outset[1,2]. Evidence in support of thisview comes from studies showingthat newborns prefer to listen tospeech compared to non-speechstimuli [3,4] and that differentareas of the brain activate forspeech and non-speech stimuli

DispatchR629

[5,6]. Behavioral studies indicatethat newborns are sensitive to theintonational pattern of their nativelanguage [7] and that infants haveheightened sensitivity to acousticdifferences that are important tolanguage [8]. However, flexibilitymust be built into the system toenable an infant to learn thelanguage that surrounds them,be it English, French or Swahili.Language acquisition hascomponents of both innateconstraints and environmentalinfluences which make it afascinating and contentiousdomain of inquiry.

Research on phonologicaldevelopment has revealeda striking developmental trajectoryin infants’ abilities to discriminatethe sounds of native languages[9,10]. Phonemes are theelementary units of meaningfulsound used to produce languages.Languages employ different setsof phonemes; English employs45 of the roughly 200 sounds usedin the world’s languages. Infantsare born with universal phoneticsensitivity: to a first approximation,they can discriminate phoneticdifferences in any of the world’slanguages. The ability to makethese perceptual discriminationsmay provide the base featuresout of which categories areconstructed. Through multimodalexperience — auditory, visual andproprioceptive — children developperceptual feature spaces wheredistinctions that signal phonemiccontrasts are perceived as distinct,whereas differences within a singlephonemic category are not [8,9].

Some of these perceptualdiscriminations have been shownto be shared with other species,particularly non-human primatesbut even chinchillas [11–13],suggesting that there may beuniversal phonetic sensitivity butonly humans go on to developlanguage skills. Over the first yearof life, human infants reveala decline in sensitivity to manynon-native phonemic distinctions,so that adults are differentiallysensitive to the phoneticdifferences marked by theirlanguage [14]. These findings havebeen used to suggest thatlanguage experience is necessaryfor the maintenance, but not for the

initial emergence, of phonemiccategories [10]. We do not knowhow general this developmentaltrajectory is across other levelsof language, for example semanticor syntactic levels [15].

A paper by Friederici et al. [16],published recently in CurrentBiology, has demonstrateddifferential brain responses basedon stress patterns that arelanguage specific. The participantswere four-month-old infants frommonolingual German or Frenchfamilies. German and French havedifferent rhythmic structures. InGerman, two-syllable words tendto be stressed on the first syllable(baba) whereas in French the sameword (when presented in isolation)is stressed on the second syllable(baba). The question was whetherfour months of listening to theirnative language would giveinfants enough experience todetect an unusual stress patternwhen presented with thepseudoword baba. The answeris a resounding yes!

Friederici et al. [16] found thatinfants responded to the samestimuli in opposite ways consistentwith the rhythmic pattern inherentin their mother tongue. The Germanbabies detected the baba stresspattern as odd, and the Frenchinfants detected the baba stresspattern as odd. The researchersused an event-related brainpotential showing a signature brainwave pattern when a deviantpattern is presented in a series ofstandard stimuli. These findingsprovide the first evidence of alanguage-specific brain responsefor the stress pattern of individualwords in four-month-old infants.They challenge current theories ofphonological development byproviding evidence that tuningspecific to infants’ native languageis already getting off the ground inthe first six months of life whereasprevious research depicted a laterdevelopmental trajectory.

Another recent article [17]reports converging evidence forinfants’ amazing language abilitiesin the first few months of life.Weikum et al. [17] found that, byfour months of age, infants can tellwhether someone is speaking intheir native tongue or a differentlanguage just by watching a silent

movie of their speech. Infants wereable to detect a different languagebased on the shapes and rhythmof the speaker’s mouth and facemovements. Whereas it is wellknown that infants have thecapacity to discriminate betweentheir own and another language onthe basis of auditory cues [7,18,19],this is the first study to show thatinfants can distinguish languagesusing only visual information. Theability to discriminate the twolanguages disappears by eightmonths of age unless the infant is ina bilingual environment providingenvironmental support formaintaining the ability.

Infants start out equally capableof learning any of the world’slanguages; then throughexperience they becomespecialists in the specific attributesof their ambient language.Together these studies show howfindings from biology interact withfindings from cognitive sciencedemonstrating that geneticpre-wiring and experience-drivenlearning interact to produce rapidlanguage acquisition skills in younginfants [20].

References1. Pinker, S. (1994). The Language Instinct

(New York: William Morrow & Co).2. Mehler, J., Dupoux, E., and Southgate, P.

(1994). What Infants Know: The NewCognitive Science of Early Development(Malden, Massachusetts: BlackwellPublishing).

3. Vouloumanos, A., and Werker, J.F. (2007).Listening to language at birth: Evidencefor a bias for speech in neonates. Dev.Science 10, 159–164.

4. Butterfield, E.C., and Siperstein, G.N.(1970). Influence of contingent auditorystimulation upon non-nutritional suckle. InThird Symposium on Oral Sensation andPerception: The Mouth of the Infant,J.F. Bosma, ed. (Springfield, Illinois:Charles C. Thomas), pp. 313–334.

5. Pena, M., Maki, A., Kovacic, D., Dehaene-Lambertz, G., Koizumi, H., Bouquet, F.,and Mehler, J. (2003). Sounds and silence:An optical topography study of languagerecognition at birth. Proc. Natl. Acad. Sci.USA 100, 11702–11705.

6. Dehaene-Lambertz, G., Dehaene, S., andHertz-Pannier, L. (2002). Functionalneuroimaging of speech perception ininfants. Science 298, 2013–2015.

7. Mehler, J., Jusczyk, P., Lambertz, G.,Halsted, N., Bertoncini, J., and Amiel-Tison, C. (1988). A precursor of languageacquisition in young infants. Cognition 29,143–178.

8. Eimas, P.D., Siqueland, E.R., Jusczyk, P.,and Vigorito, J. (1971). Speech perceptionin infants. Science 171, 303–306.

9. Jusczyk, P.W. (1997). The Discovery ofSpoken Language (Cambridge,Massachusetts: The MIT Press).

10. Werker, J.F. (1989). Becoming a nativelistener. Am. Scientist 77, 113–118.

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11. Kuhl, P.K., and Padden, D.M. (1982).Enhanced discriminability at the phoneticboundaries for the voicing feature inmacaques. Percept. Psychophys. 32,542–550.

12. Kuhl, P.K., and Miller, J.D. (1975).Speech perception by the chinchilla:Voiced-voiceless distinction in alveolarplosive consonants. Science 190,69–72.

13. Ramus, F., Hauser, M.D., Miller, C.,Morris, D., and Mehler, J. (2000).Language discrimination by humannewborns and by cotton-top tamarinmonkeys. Science 288, 349–351.

14. Werker, J.F., and Tees, R.C. (1984).Cross-language speech perception:Evidence for perceptual reorganization

Replication LicensI Did It Again

All eukaryotes use multiple controlsper cell cycle. Nevertheless, inactivamassive re-replication in Caenorhabdthis dramatic phenotype by demonstsimultaneously controls two critical l

Jerome Korzeliusand Sander van den Heuvel

One of the most fascinatingchallenges that all life forms faceis the need to maintain an intactgenome over many rounds of celldivision. Every newly formed celldemands an accurate copy of thegenome; how can this beachieved? DNA synthesis startsfrom several hundred (in yeast) toseveral hundred-thousand(Xenopus embryos) independentsites, known as ‘origins’, andcheckpoints that sense ongoingreplication can delay cell-cycleprogression to assure completion[1–3]. Replication must happenonly once, as re-firing of evena single origin may lead to geneamplification and have dramaticconsequences. Hence, alleukaryotes use multiple levels ofcontrol to prevent more than oneround of DNA synthesis withina single S phase. Despite all checksand balances, certain single genemutations lead to substantialre-replication. A recent paper inCurrent Biology [4] exposes onesuch gene as a true Achilles’ heelof re-replication control: the cul-4gene of Caenorhabditis elegansregulates two key replicationlicensing factors concurrently by

during the first year of life. Infant Behav.Devel. 7, 49–63.

15. Hespos, S.J., and Spelke, E.S. (2004).Conceptual precursors to language.Nature 430, 453–456.

16. Friederici, A., Friedrich, M., andChristophe, A. (2007). Brain responsesin 4-month-old infants are alreadylanguge-specific. Curr. Biol. 17,1208–1211.

17. Weikum, W.M., Vouloumanos, A.,Navarra, J., Soto-Faraco, S., Sebastian-Galles, N., and Werker, J.F. (2007). Visuallanguage discrimination in infancy.Science 316, 1159.

18. Nazzi, T., Bertoncini, J., and Mehler, J.(1998). Language discrimination bynewborns: Toward an understanding of

ing: Oops! .

to restrict DNA replication to oncetion of a single gene, cul-4, causesitis elegans. A novel study explainsrating that the CUL-4 E3 ligaseicensing factors: CDT-1 and CDC-6.

targeting CDT-1 for degradationand indirectly promoting CDC-6nuclear export.

The major strategy to restrictDNA replication to once per cellcycle is the temporal separation oftwo critical events: the licensing ofreplication and actual initiationof DNA synthesis [2,3,5]. The orderof these events is largely controlledby cyclin-dependent kinases(CDKs). CDK activity is low whenthe anaphase-promoting complex(APC) is active, between latemitosis and late G1. Within this timewindow, several proteins canassemble on origins to form a ‘pre-replication complex’ (Figure 1). Asa critical step in pre-replicationcomplex formation, the licensingfactors CDT-1 and CDC-6 (forsimplicity, C. elegans names,which include a dash, are also usedhere for orthologues in otherspecies) bind to origins throughassociation with the originrecognition complex (ORC). In turn,the presence of CDT-1 and CDC-6allows recruitment of a replicationhelicase, the MCM2–7 complex,onto the pre-replication complex(Figure 1). The localized presenceof MCM helicases licenses theorigin for replication. For initiationof replication, however, these MCMhelicases need to be activated,

the role of rhythm. J. Exp. Psychol. Hum.Percept. Perf. 24, 756–766.

19. Ramus, F., Nespor, M., and Mehler, J.(1999). Correlates of linguistic rhythm inthe speech signal. Cognition 73, 265–292.

20. Ramus, F. (2006). Genes, brain, andcognition: A roadmap for the cognitivescientist. Cognition 101, 247–269.

Dept. of Psychology, NorthwesternUniversity, 2029 Sheridan Road,Evanston, Illinois 60208-2710, USA.E-mail: hespos@northwestern.edu

DOI: 10.1016/j.cub.2007.06.032

which requires other kinases andadditional factors. Local unwindingof the duplex DNA by the helicaseprovides access for DNApolymerases and allows initiation.Importantly, pre-replicationcomplexes disassemble uponreplication initiation and cannotre-form till after the next anaphase.

Are all licensing componentsregulated equally, or are somemore equal? Differences exist atthis level, despite the fact thatvarious eukaryotes largely usethe same players. CDKphosphorylation of pre-replicationcomplex components is critical inall species and, at least in some,CDK inactivation can lead tore-replication [1]. CDKphosphorylation of CDC-6 triggersexport from the nucleus invertebrates [6–8]. But interferencewith this process alone does notcause re-replication. In contrast,re-replication can be triggered bymutation of CDT-1 or disruption ofits inhibitory mechanisms(reviewed in [1]). One of thenegative regulators of CDT-1is CUL-4, as was first indicatedby a previous study from theKipreos group [9]. CUL-4 is thecore-subunit of a class of‘cullin-based’ or ‘SCF-like’ E3ubiquitin ligases that targetsubstrate proteins forubiquitination and degradation. Incul-4 mutants, CDT-1 accumulatesin S phase nuclei, which pointed toCDT-1 as a potential target ofa CUL-4 E3 ligase [9]. Indeed,studies in other systems showedthat CUL-4 in association with DNAdamage binding protein 1 (DDB-1)recognizes CDT-1 as a substrate[10]. Importantly, the degradation