Naturalselectionleadstosurvivalofthefittest–which,incidentally,isnotatermDarwinhimselfused
– and to the elimination of individuals that cannot compete. As a consequence of this process, specific genetic changes accumulate in populations, resulting ultimately in enduring changes to the form and function of living species. It can explain how some beetles developed red-spotted wing cases, whilst otherslearnedtoswim,rollballsofdung,orglowinthedark.
Natural selection is a profound idea, which has significance beyond biology. It has both explanatory powerandpracticalutilityinseveralotherdisciplines,notleasteconomicsandcomputerscience.Today, for example, some aspects of software and some engineered components of machines, such as aircraft, areoptimizedbyalgorithmsthatmimicnaturalselection.
These products are evolved, rather than designed in the traditional sense. For evolution by natural selectiontotakeplace,livingorganismsmusthavethreecrucialcharacteristics.
First,theymustbeabletoreproduce.
Second, they must have a hereditary system, whereby information defining the characteristics of the organismiscopiedandinheritedduringtheirreproduction.
Third,thehereditarysystemmustexhibitvariability,andthisvariabilitymustbeinheritedduringthe reproductiveprocess.Itisthisvariabilitythatnaturalselectionoperatesupon.Ittransformsaslowand randomlygeneratedsourceofvariabilityintotheapparentlyboundlessandconstantlychangingrangeof lifeformsthatflourisharoundus.
Additionally, for this to work efficiently, living organisms must die. That way, the next generation, potentiallycontaininggeneticvariantsthatgivethemacompetitiveedge,canreplacethem.
Thethreenecessarycharacteristicsemergedirectlyfromtheideasofthecellandthegene.Allcells reproduceduringthecellcycleandallcellshaveahereditarysystemmadeupofgenes,whicharecopied and inherited on the chromosomes during mitosis and cell division. Variation is introduced by the appearanceofchancemutationsthatchangeDNAsequences–liketheonethatledmetodiscoverthe cdc2 gene – which result from either rare mistakes during the copying of the double helix, or environmentaldamagetotheDNA.Cellsrepairthesemutations,buttheyarenotcompletelysuccessful.
Iftheywere,allindividualsofaspecieswouldbeidenticalandevolutionwouldstop.Thismeanstheerror rate itself is subject to natural selection. If that error rate is too high the information stored by the genome will degenerate and become meaningless, and if errors are too rare, the possibility for evolutionary change is reduced. Over the long term, the most successful species will be those that can maintaintherightbalancebetweenconstancyandchange.
In complex eukaryote organisms, further variability is introduced during the process of sexual reproduction,whenpartsofchromosomesarereshuffledduringthecelldivisionsthatproducesexcells (also known as germ cells: sperm cells and egg cells in animals, and pollen and ovules in flowering plants), which are made by the process called meiosis. That is the main reason siblings are genetically differentfromeachother:iftheirparents’genesarelikeadeckofcards,theyareeachdealtadifferent genetic‘hand’.
Many other organisms introduce variation by exchanging DNA sequences directly, between different individuals.Thisiscommoninlesscomplexorganismslikebacteria,whichcanswapgenesbetweenone another,butalsowithmorecomplexorganisms.Thisprocessiscalledhorizontalgenetransfer.Itisoneof the reasons the genes that make certain bacteria resistant to antibiotics can spread rapidly through wholepopulationsofbacteria,andevenfromoneunrelatedspeciestoanother.Horizontalgenetransfer also makes it harder to trace some lineages back through evolutionary time, since it means that the inheritanceofgenescanflowfromonebranchofthetreeoflifeintoanother.
Whatever the source of genetic variability, to fuel evolutionary change it must persist during subsequent reproduction and generate populations of organisms that vary across every possible dimension, whether that’s subtle differences in disease resistance, attractiveness to mates, food tolerance, or any number of other characteristics. Natural selection can then act to sift the helpful variantsfromtheharmful.
Oneprofoundconsequenceofevolutionbynaturalselectionisthatalllifeisconnectedbydescent.This means that as the tree of life is traced backwards, the branches increasingly converge into bigger branchesandeventuallyintoasingletrunk.Theconclusiontherefore,isthatwehumansarerelatedto every other life form on the planet. To some, like the apes, we are closely related, because we are on adjacenttwigsattheedgeofthetree,andtoothers,likemyyeast,therelationshipismuchmoredistant, becauseweonlybecome‘joined’muchfurtherbackintime,closertothemaintrunkofthetreeoflife.
OurfundamentalconnectednesstootherlifewasbroughthometomewhenIwenttrekkingthrough the humid and verdant Ugandan rainforest, in search of mountain gorillas. Following my guide, we suddenly came upon a family group. I found myself sitting opposite a magnificent silverback, who was squattingunderneathatree,justtwoorthreemetresawayfromme.Ibrokeoutintoasweat,anditwas not just because it was hot and humid. As a geneticist, I knew that he and I shared about 96% of our genes,butthatbaldnumbercanonlytellpartofthestory.Ashisintelligent,deepbrowneyeslockedmy gaze,Isawmanyaspectsofmyhumanityreflectedbackatme.Thoseapeswerecloselyattunedtoeach other and also to us humans. Much of their behaviour was inescapably familiar; their empathy and curiosity obvious. The silverback and I contemplated each other for several minutes. It was like a conversation.Thenheputoutahand,bentdoubleafive-centimetrediametersapling(washetryingto tell me something?) and slowly climbed the tree, all the time holding me in his gaze with those penetrating eyes. This dramatic and moving encounter emphasized for me quite how closely we are relatedtothesemagnificentcreatures.Thatconnectednessextendsbeyondthegorillatootherapes,to mammalsandotheranimals,andeven,viamoreancientforksinlife’ssharedfamilytree,toplantsand microbes. This, to me, is one of the best arguments for why humanity should care about the entire biosphere;allthedifferentlifeformsthatshareourplanetareourrelatives.
IbecameawareofourdeeprelatednesstootherlivingthingsinanevenmoreunexpectedwaywhenI decidedtoaskwhetherfissionyeastandhumancellscontrolledtheircellcyclesinthesameway.Iasked this question during the 1980s, when I found myself working in a cancer research institute in London.
Sincecanceriscausedbyaberrantcelldivisionofhumancells,mostofmycolleagues,workinginother labs,veryunderstandably,weremuchmoreinterestedtoknowwhatcontrolledthecellcycleinhumans ratherthaninyeast.BythattimeIknewwhatcontrolledcelldivisioninyeast:itwasacellcyclecontrol mechanismwith cdc2,thatcrucialgenewiththeuninspiringname,atitsverycentre.
I wondered if it could possibly be the case that human cell division was also controlled by a human version of the same gene, cdc2? This seemed very unlikely, given that yeasts and humans are so very differentandlasthadanancestorincommon1.2to1.5billionyearsago(thatis,1,200to1,500million yearsago).Toputthathugeexpanseoftimeinperspective,dinosaursbecameextincta‘mere’65million
years ago, and the first simple animals appeared around 500–600 million years ago. If I’m completely honest, it was more than slightly preposterous to believe that such distant relatives could have cells whosereprod
uctionwascontrolledinthesameway.Nevertheless,wehadtofindout.
ThewayMelanieLeeinmylabtackledthisquestionwastotryandfindahumangenethatfunctioned thesamewayasdid cdc2infissionyeast.Todothis,shetookfissionyeastcellsthatweredefectivein cdc2 and so could not divide, and ‘sprinkled’ on them a gene ‘library’ that was made up of many thousands of pieces of human DNA. Each piece of DNA contained a single human gene. Melanie used conditionsthatensuredthatthemutantyeastcellwouldusuallyonlytakeuponeortwogenes. If it so happenedthatoneofthesegeneswasthehumanequivalentofthe cdc2geneand ifitfunctionedinthe samewayinbothhumanandyeastcells,and ifthehuman cdc2genecouldgetintotheyeastcells,then the cdc2 mutant cells might just regain the ability to divide. If all that went right, they should form coloniesthatMelaniecouldseeonaPetridish.Youmayhavenoticedtherewereseveral‘ifs’inthisplan.
Didwethinktheexperimentwouldwork?Probablynot,butitwasworthashot.
And,amazingly,itdidwork!ColoniesgrewonthePetridishandwewereabletoisolatethestretchof human DNA that had successfully stood in for the cdc2 gene that is so vital for yeast cell division. We sequencedthisunknowngeneandsawthatthesequenceoftheproteinitmadewasverysimilartothe yeastCdc2protein.Itwasobviousthatwewerelookingattwohighlyrelatedversionsofthesamegene.
Sosimilarweretheythatthe humangenecouldcontrolthe yeastcellcycle.
Thisunexpectedresultledustoafar-reachingconclusion.Giventhatfissionyeastandhumansareso distantlyrelatedinevolution,itwasverylikelythatcellsineveryanimal,fungusandplantontheplanet controlledtheircellcycleinthesameway.Theyalmostcertainlyalldependedontheactionofagenethat was very similar to yeast’s cdc2 gene. And, what is more, even as these different organisms gradually evolved over aeons of evolutionary time to take on countless different forms and lifestyles, the core controlsofthismostfundamentalprocesshadbarelychanged. Cdc2isaninnovationthathasenduredfor morethanonebillionyears.
Allofthisreinforcedmyconvictionthatunderstandinghowhumancellscontroltheirdivision,whichis crucial for understanding how our bodies change as we grow, develop, suffer diseases and degenerate acrossourlifespans,canbestudiedprofitablyinawiderangeoflivingorganisms,includingthesimple yeast.
Naturalselectionnotonlytakesplaceduringevolution;itisalsotakingplaceatthelevelofthecells insideourbodies.Cancerstartswhengenesimportantforcontrollingthegrowthanddivisionofcellsare damaged or rearranged, leading to cells that divide in uncontrolled ways. Just like evolution within a populationoforganisms,thesepre-cancerousorcancerouscellscan,iftheyevadethebody’sdefences, gradually overtake the population of unaltered cells that make up the tissue. As the population of damagedcellsgrows,thereisagreaterchanceoffurthergeneticchangestakingplacewithinthesecells, leading to an accumulation of genetic damage and the generation of increasingly aggressive cancerous cells.
Thissystemhasthethreecharacteristicsnecessaryforevolutionbynaturalselection:reproduction,a hereditarysystem,andtheabilityofthehereditarysystemtoexhibitvariability.Itisparadoxicalthatthe verycircumstancesthatallowedhumanlifetoevolveinthefirstplacearealsoresponsibleforoneofthe mostdeadlyhumandiseases.Morepractically,italsomeansthatpopulationandevolutionarybiologists shouldbeabletocontributesignificantlytoourunderstandingofcancer.
Evolution by natural selection can bring about great complexity and the apparent purposefulness of livingthings.Itdoesthiswithoutanycontrollingintellect,definedendgoal,orultimatedrivingforce.It sidestepscompletelytheargumentsinvokingadivineCreator,asmadebyPaleywithhisimaginedpocket watch,andmanyothersbeforeandsince.Anditleavesme,forone,inastateofconstantwonder.
Learningaboutevolutionalsohadaratherdramaticimpactonthecourseofmylife.Mygrandmother wasaBaptist,soweusedtogotothelocalBaptistchurcheverySunday.IknewtheBiblewell(stilldo), andevenhadthoughtsofbecomingaminister,perhapsevenamissionary!Then,aroundthetimeIsaw that brimstone butterfly in my garden, I was taught about evolution by natural selection at school. The scientificexplanationforlife’sabundantdiversitywasclearlyindirectconflictwiththebiblicalaccount.
Tryingtomakesenseofthisdiscrepancy,IwenttotalktomyBaptistminister.Isuggestedtohimthat when God was speaking about the Genesis account of creation, he was explaining what happened in termsthatwouldmakesensetoanuneducated,pastoralpopulationtwoorthreethousandyearsago.I saidthatweshouldperhapstreatitmorelikeamyth,butthat,inreality,Godhaddevisedanevenmore wonderfulmechanismforcreation,byinventingevolutionbynaturalselection.Unfortunatelymyminister didnotseeitlikethatatall.HetoldmeIhadtobelievetheliteraltruthofGenesisandsaidthathewould prayforme.
Thus began my gradual descent from religious belief to atheism, or to be more precise, sceptical agnosticism.Isawthatdifferentreligionscanhaveverydifferentbeliefs,andthatthosedifferentcreeds couldbeinconsistentwitheachother.Sciencegavemearoutetoamorerationalunderstandingofthe world. It gave me greater certainty too, stability even, and a better way to pursue truth; the ultimate objectiveofscience.
Evolutionbynaturalselectiondescribeshowdifferentlifeformscancomeaboutandattainpurpose.It isdrivenbychanceandsteeredbythenecessityofgeneratingincreasinglyeffectivelifeforms.However, itdoesnotgivemuchinsightintohowlivingorganismsactuallywork.Forthatwehavetoturntothenext twoideas,thefirstofwhichis lifeaschemistry.
4.LIFEASCHEMISTRY
OrderfromChaos
Most people would probably look at the world around them and divide it into two main types of thing: thosethatarealiveandthosethatareclearlynot.Livingorganismsstandoutbecausetheyarethingsof action; they behave with purpose, reacting to their surroundings and reproducing themselves. None of thesecharacteristicsapplytothingsthatarenotliving,likeapebble,amountain,orasandybeach,for example.Indeed,ifweweretostepbackintimeacoupleofhundredyears,beforethedevelopmentof theideasdescribedinthisbook,wemightwellhaveconcludedthatearthlylifeisdirectedbymysterious forcesthatareuniquetolivingthings.
Thiswayofthinkingiscalled‘vitalism’,anditsoriginstracebacktotheclassicalthinkersAristotleand Galen,andprobablyevenfurther.Evenforthemostrationalandscientificamongus,itishardtoentirely abandonsuchthinking.Ifyou’veeverseensomeonedie,youwillknowitcanseemverymuchasifsome inexplicablesparkoflifehasbeenabruptlyextinguished.
Vitalistexplanationsareappealingsincetheyseemtoprovideacomfortingsolutiontowhatourminds struggle to grasp. But we can in fact now be certain that we do not need to invoke any form of magic.
Most aspects of life can be understood rather well in terms of physics and chemistry, albeit an extraordinaryformofchemistrythatishighlyorderedandorganized,andofasophisticationthatcannot be matched by any inanimate process. For me, this explanation is more awe-inspiring than any kind of beliefthatlifeisdirectedbymysteriousforcesthatliebeyondthereachofscientificscrutiny.
Thisideathatlife ischemistryrathersurprisinglyhaditsoriginsinstudiesoffermentation,theprocess bywhichthesimplemicrobeyeastmakesalcoholduringtheproductionofbeerandwine.Thishasbeena long-standinginterestofhumanity.
Infact,myownlifehasbeeninfluencedquitealotbyfermentation,andnotjustbecauseIamrather fondofbeermyself;sittingaloneco
ntemplatingtheworldinanemptypubearlyintheeveningisareal pleasure.WhenIleftschoolatseventeenyearsofage,IknewIwantedtostudybiology,butIcouldn’tget aplaceatuniversity.Atthattimeabasicforeignlanguagequalification,achievedviaanexamknownas an O-level, was a compulsory entry requirement for all undergraduate degree programmes, but I managedtofailmyFrenchexamsixtimes,probablyaworldrecordinO-levelfailures!SoIdidn’tgoto university,butwenttoworkinsteadasatechnicianinamicrobiologylaboratorylinkedtoabrewery.
Partofmyjobeachdaywastomakeallthenutrient-containingconcoctionsthatthescientistsneeded to grow their microbes. I soon realized that they nearly always placed the same daily order, so I could makeitallupinabigbatchonMonday,whichwouldthenlastallweek.IwenttoseemybossVicKnivett (who, incidentally, was a Georgian dancer in his spare time, a fact I discovered when I found him one evening performing an energetic Cossack-like kicking dance on top of one of the laboratory benches!).
Generously,hesuggestedIcarryoutaresearchprojecton Salmonellainfectionsofhens’eggs.Iwasan eighteen-year-oldinheaven,doingexperimentseveryday,pretendingtobearealscientist.
At some point during that year in the brewery, a sympathetic professor at Birmingham University calledmeforaninterview,andeventuallypersuadedtheuniversitytooverlookmyweaknessesinforeign languages so I could start a biology degree in 1967. Ironically, considering my early struggles with the language,thirty-fiveyearslaterIwasgrantedanawardcalledtheLégiond’honneurbythePresidentof Franceformyresearchonyeast.IevenhadtogivemyacceptancespeechinFrench!However,despite studyingyeastformostofmylife,Ihavenevermadeadropofeitherwineorbeermyself.
Paul Nurse - What Is Life Page 5
