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INTRODUCCIÓN A lo largo de la historia el hombre siempre ha tratado de buscar la razn de por !u" las cosas son de esa manera # buscar resol$er los enigmas !ue lo rodean% &a estructura interna del ser humano # !u" la compone' no se ha sal$ado de esta curiosidad% Uno de los enigmas !ue se ten(a durante el siglo ))' *ue de cmo se traspasaba el material gen"tico de generacin en generacin' !u" lo hac(a # como lo hac(a% Al principio se cre(a !ue las prote(nas eran las !ue transportaban este material+ pero luego' gracias Castre5n 6abriell ,ar(a 7ernanda estudios #
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9IO&O6>A II: ?O&4DAD A6UI&AR RA9A?A
ADN0' con su experimento de los ra#os )' lograron descubrir la estructura interna del ADN /la doble h"lice0 # !ue el patr patrim imon onio io gen" gen"titico co del del ser ser humano se basa en 12 pares de cromosomas% Adem3s se comprob con esto' !ue las estructuras !ue tran ranspor portaban gen"tico
eran
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O9@4TIO 4n el siguiente traba5o # ma!ueta !ue se realiz' se intent representar al ADN # as(' tener una $isin m3s amplia de la estructura de este% De cmo est3n ubicadas las bases nitrogenadas /adenina' timina' citosina # guanina0' brindar in*ormacin acerca de la estructura # *uncionamiento del ADN # elaborar la estructura del ADN en la !ue se identi*i!uen las estructuras de este% 4l pro#ecto busca lograr conocimiento acerca del ADN apo#3ndose en el uso de material did3ctico !ue e5empli*i!ue la estructura # *uncionamiento del mismo%
ADN: ÁCIDO D4?O)IRRI9ONUC D4?O)IRRI9ONUC&4ICO &4ICO 4l 3cido desoxirribonu desoxirribonucleico cleico'' abre$iado abre$iado como ADN' ADN' es un 3cido nucleico nucleico !ue contiene contiene las instrucciones gen"ticas usadas en el desarrollo # *uncionamiento de todos los organis organismos mos $i$os $i$os # algunos algunos $irus% $irus% Respons Responsable able de su transm transmisi isin n heredit hereditari aria' a' su *unc *unci in n prin princi cipa pall cont contie iene ne las las inst instru rucc ccio ione ness nece necesa sari rias as para para cons constr trui uirr otro otross comp compon onent entes es de las las c"lul c"lulas as'' como como las las prot prote( e(na nass # las las mol" mol"cu cula lass de ARN% RN% &os &os segmentos de ADN !ue lle$an esta in*ormacin gen"tica son llamados genes% Desde el punto de $ista !u(mico' el ADN es un pol(mero de nucletidos' es decir' un polinucletido% Un pol(mero es un compuesto *ormado por muchas unidades simples conectadas entre s(' cada nucletido' # cada nucletido' a su $ez' est3 *ormado por un azBcar /la desoxirribosa0' una base nitrogenada /!ue puede ser adenina A' timina T' citosina C o guanina 60 # un grupo *os*ato !ue actBa como enganche de cada
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cadena de nucletidos' en la !ue las dos hebras est3n unidas entre s( por unas conexiones denominadas puentes de hidrgeno% ara !ue la in*ormacin !ue contiene el ADN pueda ser utilizada por la c"lula' debe copiarse en primer lugar en unas cadenas de nucletidos' m3s cortas # con unas unidades di*erentes' llamados ARN% &as mol"culas de ARN se copian exactamente del ADN mediante un proceso denominado transcripcin% transc ripcin% Una $ez procesadas en el nBcleo celular' celular' las mol"culas de ARN pueden salir al citoplasma para su utilizaci utilizacin n posterior% posterior% &a in*ormacin contenida en el ARN se interpreta usando el cdigo gen"tico' !ue espe especci*ic i*ica a la secu secuen enci cia a de los los amin amino3 o3ci cido doss de las prot prote( e(na nas' s' segB segBn n una una correspondenci correspondencia a de un triplete de nucletidos nucletidos /codn0 para cada amino3cido% amino3cido% 4sto es' la in*ormacin gen"tica /!u" prote(nas se $an a producir en cada momento del ciclo de $ida de una c"lula0 se halla codi*icada en las secuencias de nucletidos del ADN # debe debe traduc traducirse irse para para poder poder *uncio *uncionar nar%% Tal traducc traduccin in se realiz realiza a usando usando el cdigo cdigo gen"tico !ue permite el ensamblado de largas cadenas de amino3cidos /las prote(nas0 en el citoplasma de la c"lula% &as secuencias de ADN !ue constitu#en la unidad *undamental' *(sica # *uncional de la herencia se denominan genes% Cada gen contiene una parte !ue se transcribe a ARN # otra !ue se encarga de de*inir cu3ndo # dnde deben expresarse% &a in*ormacin contenida en los genes /gen"tica0 se emplea para generar ARN # prote(nas' !ue son los los comp compone onent ntes es b3si b3sicos cos de las c"lu c"lula las' s' mu# impor importa tant ntes es en la const construc rucci cin n de org3nulos u organelos celulares' entre otras *unciones% Dentro de las c"lulas' el ADN est3 organizado en estructuras llamadas cromosomas !ue' !ue' duran durante te el cicl ciclo o celu celula lar' r' se dupl duplic ican an ante antess de !ue !ue la c"lul c"lula a se di$i di$ida da%% &os &os organismos eucariontes /como animales' plantas # hongos0 almacenan la ma#or parte de su ADN dent dentro ro del del nBcle nBcleo o celu celula lar' r' una una m(ni m(nima ma part parte e en elem elemen ento toss celul celular ares es llamados mitocondrias+ en los plastos # los centros organizadores de microtBbulos o cent centr( r(ol olos os'' en caso caso de tene tenerl rlos% os% &os &os orga organi nism smos os proc procari ariont ontes es /como /como bact bacteri erias as #
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dot3ndolo de una estructura tridimensional determinada # regulando su expresin% &os *actores de transcripcin reconocen secuencias reguladoras del ADN # especi*ican la pauta de transcripcin de los genes% 4l material gen"tico completo de un con5unto cromosmico cromosmico se denomina denomina genoma #' con pe!ueFas pe!ueFas $ariaciones' $ariaciones' es caracter(sti caracter(stico co de cada especie%
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GI?TORIA 4l ADN lo aisl por primera $ez en =H;' el m"dico suizo 7riedrich 7riedr ich ,iesc ,iescher her mientras traba5aba en la Uni$ersidad de Tubi Tubing nga% a% ,iesc ,iescher her reali realiza zaba ba exper experim imen ento toss acer acerca ca de la comp compos osic ici in n !u( !u(mica mica del del pus de $end $endas as !uir !uirBr Brgi gica cass desechadas cuando not un precipitado de una sustancia desconocida !ue caracteriz !u(micamente m3s tarde% &o llam nucle(na' debido a !ue lo hab(a extra(do a partir de nBcleos celu elulares res% ?e necesi esitaron ron cas casi JK aFos Fos de in$estigacin para poder identi*icar los componentes # la estr estruc ucttura ura de los 3cid 3cidos os nucleicos% 4n == ho hoebus ebus &e$ &e$ene ene identi*ic !ue un nucletido est3 *ormado por una base nitrogenada' un azBcar # un *os*ato% &e$ene sugiri !ue el ADN generaba generaba una estructura con *orma de solenoide /muelle0 con unidades de nucletidos unidos a tra$"s de los grupos *os*ato%
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4n =2K &e$ene # su maestro Albrecht maestro Albrecht Lossel probaron Lossel probaron !ue la nucle( nucle(na na de ,iesch ,iescher er es un 3cido 3cido desoxir desoxirrib ribonu onucle cleico ico /ADN0 *ormado por cuatro bases nitrogenadas /citosina /C0' timina /T0' adenina /A0 # guanina /60' el azBcar desoxirribosa # un grupo rupo *os* os*ato' ato' # !ue' !ue' en su est estruct ructur ura a b3s b3sica' ica' el nucletido est3 compuesto por un azBcar unido a la base # al *os*ato% ?in embargo' &e$ene pensaba !ue la cadena era corta # !ue las las base basess se repe repet( t(an an en un orde orden n *i5o *i5o%% 4n =2J =2J -illiam Astbur# produ5o Astbur# produ5o el primer patrn de di*raccin de ra#os ) !ue mostraba !ue el ADN ten(a una estructura regular% &a *uncin biolgica del ADN comenz a aclararse en =1H' con con una una seri serie e b3si b3sica ca de expe experi rime ment ntos os de la gen" gen"titica ca mode modern rna a real realiz izad ados os por por 7rederi 7rederic. c. 6ri* 6ri**ith *ith'' !uie !uien n esta estaba ba trab traba5 a5an ando do con con cepa cepass Mlis Mlisas as /?0 o Mrug Mrugosa osas s /R0 /R0 de la bacteria neumococcus /causante de la neumon(a0' segBn la presencia /?0 o no /R0 de una c3psula azucarada' !ue es la !ue con*iere $irulencia /capacidad /capacidad de un microorganis microorganismo mo de producir en*ermedad0% &a in#eccin de neumococos ? $i$os en ratones produce produce la muerte de "stos' # 6ri**ith 6ri**ith obser$ !ue' si in#ectaba ratones con neumococos R $i$os o con neumococos ?
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Como las bacterias muertas no pudieron haberse multiplicado dentro del ratn' 6ri**ith razon razon !ue !ue deb( deb(a a produ produci cirs rse e algB algBn n tipo tipo de camb cambio io o tran trans* s*orm ormaci acin n de un tipo tipo bacteriano a otro por medio de una trans*erencia de alguna sustancia acti$a' !ue denomin principio trans*ormante% 4sta sustancia proporcionaba la capacidad a los neumococos
R de
produ produci cirr una una c3psula azuca azucara rada da #
Cepa:
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4n los siguie siguiente ntess = aFos' aFos' estos estos experi experimen mentos tos inicia iniciales les se replic replicaro aron n mezcla mezclando ndo distintos tipos de cepas bacterianas muertas por el calor con otras $i$as' tanto en ratones /in $i$o0 como en tubos de ensa#o /in $itro0%
In $i$o:
In $itro:
4xamen serolgico:
8ue 8ue ocur ocurre re o tien tiene e luga lugar r dentro de un organismoS% In $i$o' se re*iere a la expe experi rime ment ntac aciin hech hecha a dentro o en el te5ido te5ido $i$o de un organismo $i$o
/Del lat(n: dentro del $idrio0 ?e re*ier re*iere e a una una t"cni t"cnica ca para realizar un determinado determinado experimento experimento en un tubo de ensa#o' o generalmente en un ambiente controlado *uera de un organismo $i$o%
Tiene ene como como *in *in el conoc onocer er la exposicin o presencia pre$ia de un microo microorgan rganism ismo o patgen patgeno o en part partic icul ular ar'' # a part partir ir de ella ella la capaci acidad de res respuesta del indi$iduo a tal in*eccin% ara ello se debe ebe toma omar una mues muestr tra a de sang sangre re%% ?e pued puede e usar la sangre total o tomar solo el suero' el cual se obtiene luego de centri*ugar la sangre pre$ pre$ia iame ment nte e coag coagul ulad ada' a' para para eliminar las c"lulas sangu(neas de la reaccin% 4ste examen se realiza tambi"n para para descart descartar ar sospech sospechas as sobre sobre alguna in*eccin' si se encuentran razo razone ness para para pron pronos ostitica carr una una en*ermedad existente' el examen se puede repetir a las dos semanas de la primera toma de muestra sangu(nea% &a sero serolo log( g(a a perm permitite e dete detect ctar ar
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4stos in$estigadores extra5eron la *raccin acti$a /el *actor trans*ormante0 #' mediante an3lisis !u(micos' enzim3ticos # serolgicos' obser$aron !ue no conten(a prote(nas' ni l(pidos no ligados' ni polisac3ridos acti$os' sino !ue estaba constituido principalmente por Suna *orma $iscosa de 3cido desoxirribonucleico altamente polimerizadoS' es decir' ADN% 4l ADN extra(do de las cepas bacterianas ? muertas por el calor' lo mezclaron Sin $itroS con cepas R $i$as+ el resultado *ue !ue se *ormaron colonias bacterianas ?' por lo !ue se conclu# clu# !ue el *acto ctor o principio trans*ormante era el ADN% A pesar de !ue la identi*icacin del ADN como como prin princi cipi pio o tran trans* s*or orma mant nte e aBn aBn tard tard $arios aFos en ser uni$ersalmente aceptada% 4ste 4ste desc descub ubri rimi mien ento to *ue *ue deci decisi si$o $o en el conoc conocim imie ient nto o de la base base mole molecu cula larr de la herencia' # constitu#e el nacimiento de la gen"tica molecular% m olecular% 7inalmente' el papel exclusi$o del ADN en la heredabilidad *ue con*irmado en =1 medi median ante te los los expe experi rime ment ntos os de Al*red Gershe# # ,artha Chase Chase'' en los cua cuales comprobaron !ue el *ago T1 transmit(a su in*ormacin gen"tica en su ADN' pero no en su prote(na%
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4n cuanto a la caracterizacin !u(mica de la mol"cula' 4rQin Charga** realiz en =PK algunos experimentos !ue le sir$ieron para establecer las proporciones de las bases nitrogenadas en el ADN% Descubri !ue las proporciones de purinas eran id"nticas a las de pirimidinas' pirimidinas' la Me!uimolecu Me!uimolecularida laridad d de las bases /AVT' /AVT' 6VC0' 6VC0' el hecho de !ue la cantidad de 6WC en una determinada mol"cula de ADN no siempre es igual a la cantidad de AWT # puede $ariar desde el 2; hasta el JK por ciento del contenido total% Con toda oda est esta in* in*orma ormaccin in # 5unt 5unto o con con los dat datos de di* di*racc racci in n de ra# ra#os ) proporcionados por Rosalind 7ran.lin' @ames -atson # 7rancis Cric. propusieron en =2 el modelo de la doble h"lice de ADN para representar la estructura tridimensional
Di*racci Di*rac cin n de ra# ra#os os ) del ADN
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-atson' Cric. # -il.ins recibieron con5untamente' en =;1' despu"s de la muerte de Rosalind 7ran.lin' el remio Nobel en 7isiolog(a o ,edicina% ?in embargo' el debate continBa sobre !ui"n deber(a recibir cr"dito por el descubrimiento%
ROI4DAD4? 4l ADN es un largo pol(mero *ormado por unidades repetiti$as' los nucletidos% Aun!ue cada unidad indi$idual !ue se repite es mu# pe!ueFa' los pol(meros de ADN pueden ser mol"culas enormes !ue contienen millones de nucletidos% or e5emplo' el cromosoma humano m3s largo' el cromosoma nBmero =' tiene aproximadamente 11K millones de pares de bases% 4n
los
organismos
$i$os' el ADN
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como
i di id
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4l modelo de estructura en doble h"lice *ue propuesto en =2 por @ames -atson # 7rancis' despu"s de obtener una imagen de la estructura de doble h"lice gracias a la re*raccin por ra#os ) hecha por Rosalind 7ran.lin% 4l "xito de este modelo radicaba en su consistencia con las propiedades *(sicas # !u( !u(mica micass del del ADN% DN% 4l est estudio udio most mostra raba ba'' adem3s' !ue la complementariedad de bases pod(a ser rele$ante en su replicacin' # tambi"n la importancia de la secuencia de bases como portadora de in*ormacin gen"tica%
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4structura de soporte: &a soporte: &a estructura de soporte de una hebra de ADN est3 *ormada por unidades alternas de grupos *os*ato # azBcar /desoxirribosa0% 4l azBcar en el ADN es una pentosa' concretamente' la desoxirribosa% Ácido *os*rico:?u *os*rico:?u *rmula !u(mica es G2OP% Cada nucletido puede contener uno /mono*os*ato: A,0' dos /di*os*ato: AD0 o tres /tri*os*ato: AT0 grupos de 3cido *os*rico' aun!ue como monmeros constitu#entes de los 3cidos nucleicos solo aparecen en *orma de nuclesidos mono*os*ato /A,0% Desoxirribosa:4s Desoxirribosa: 4s un monosac3rido de 3tomos de carbono /una pentosa0 deri$ado de la ribosa' !ue *orma parte de la estructura de nucletidos del ADN% ?u *rmula es CG=KOP% Una de las principales di*erencias entre el ADN # el ARN es el azBcar' pues en el ARN la 1Xdesoxirribosa del ADN es reemplazada por una pentosa alternati$a' la ribosa%
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9ases nitrogenadas: &as cuatro bases nitrogenadas ma#oritarias !ue se encuentran en el ADN son la adenina /A0' la citosina /C0' la guanina /60 # la timina /T0% Cada una de estas cuatro bases est3 unida al armazn de azBcarX*os*ato a tra$"s del azBcar para *ormar el nucletido completo /baseXazBcarX*os*ato0% &as bases' se clasi*ican en dos grupos: las bases bases pBric pBricas as o puri purina nass /adeni /adenina na # guan guanin ina0 a0 # las las bases bases piri pirimi mid( d(ni nica cass o bases bases pirim(dicas o pirimidinas /citosina # timina0% 4n los 3cidos nucleicos existe una !uinta base pirimid(nica' denominada uracilo /U0' !ue normalmente ocupa el lugar de la timina en el ARN%
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Citosina: 4n el cdigo gen"tico gen"tico se representa con la letra C% &a citosina siempre se empare5a en el ADN con la guanina de la cadena complementaria mediante un triple enlace' CZ6% ?u *rmula !u(mica es CPGN2O% &a citosina se descubri en =HP' al aislarla del te5ido del timo de carnero%
7UNCION4? 9IO&Ó6ICA?
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Replicación del ADN
&a replicacin del ADN es el proceso por el cual se obtienen copias o r"plicas id"nticas de una mol"cula de ADN% &a replicacin es *undamental para la trans*erencia de la in*ormacin gen"tica de una generacin a la siguiente #' por ende' es la base de la herencia% 4l mecanismo consiste esencialmente en la separacin de las dos hebras de la doble h"lice' las cuales sir$en de molde para la posterior s(ntesis de cadenas complementarias a cada una de ellas' !ue lle$ar3 por nombre ARNm% 4l resultado *inal son son dos dos mol" mol"cu cula lass id"nt id"ntic icas as a la origi origina nal%l% 4ste 4ste tipo tipo de repli replica caci cin n se denom denomin ina a semiconser$ati$a debido a !ue cada una de las dos mol"culas resultantes de la duplicacin presenta una cadena procedente de la mol"cula SmadreS # otra reci"n
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Transcripción y traducción
4n un gen' la secuencia de nucletidos a lo largo de una hebra de ADN se transcribe a un ARN mensa5ero /ARNm0 # esta secuencia a su $ez se traduce a una prote(na !ue un organismo es capaz de sintetizar o SexpresarS en uno o $arios momentos de su $ida' usando la in*ormacin de dicha secuencia%
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mol" mol"ccula ula de ARN de trans rans*e *ere renc ncia ia /ARN /ARNtt o tRNA0 RNA0 !ue cont conten enga ga el trip triple lette complementario' denominado anticodn%
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Enzimas que modifican el ADN
Nucleasas # ligasas &as nucleasas' son enzimas !ue catalizan la ruptura de los enlaces *os*odi"ster' como
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gen"tica%
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necesarias para muchos procesos en los !ue inter$iene el ADN' como la replicacin del ADN # la transcripcin% &as helicasas son unas prote(nas !ue pertenecen al grupo de los motores moleculares%
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4n la replicacin del ADN' una ADN polimerasa dependiente de ADN realiza una copia de ADN a partir de una secuencia de ADN% &a precisin es $ital en este proceso' por lo !ue muchas de estas polimerasas tienen una acti$idad de $eri*icacin de la lectura
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