Seminar, Brandeis Univorsity. April 23, 1958 Alteration of Gene action by Genetic Mechanisms. I, The Problem: what tyvoes of senetvic mechanisms bring about abrunt and C distinct chances in gene action in specifie cells during development. te chances occur ted with 2. why protlem arises: Recently become aware tnat fen to nuclei during development and are probably ass developmental processes. c |» | etl oC 3. Development of gene theory: First nalf of century: a)e Based mainiy on selected mutants b). Mutants segregated in clear-cut fasnion in herbdiby. c)}. Mutants -- inecnsequential tyes: Drosophila - white eves, voles, body color, curled wings, folked bristle ete, ze = Anthocranin cignenits in olent and kernel, starch tyves in kernel, cte,. ce), Arrangencnts of change in Linear order in chrcmoscne, d). Repeated occurrences of change at one locus -- same vhonotyne altered, e). Chre a me beravior -- reduplkcation - sister chromatids alike: sed on gorme line for continuation of mutant trme,. ft). Postulate: All nuclei of individual nave same renetic ecnstitvtion: axtrapolaticn, Not direct evidence, e). Effect on enbryology: Confusion, Weiss - 19) +: Clear statement of ccnfusion: Healized sone divferentiaticn related to chanre in votential of nucleus. tried to ask feneticists for a nechanism, wpled to find evidence in genetics for differentiation of nuclei, lie Waat was known of differe:tion of nuclei: a). Gorm line - sot aside early - vrotected from chang b). Somass Unromoso oe changes: Poly ploid nuclei Polytene nuclei Loss of ce tain ehromesomes in certain nuclei Non-disjunctions of certain chromcsomes at s ecific divisions Loss of whole set of chrovosoves in certain nuclet Loss of part of a chromosone - specific in csrtein division Serrersation of polvytene chromosomes -~ reduction somatic nesult: No difect effect on geneticists -- did not alter views, ce), Chenses in gene action know: Position effect | in Drosopiila - change in position of resnect to netoroe rovatin and euc vmmatin -- varies 8 individval -- differentisl action of genes in dif Varic geti LOD so-called mutable genes: “nown in all wide-spread prenomena, uxceedingly dif cells covld dixfer in tyve of control: LXAMDLes! (1) Cne - chenged rate of subsequent mutation - increased sister cell ~ decrensed rate, (2) Cne cell = mutation 0 © oo. é eister cell - chanced pate of mutati f). Cne basic pattern -- controlled turning on and off of gene action during development. Genetic mechanism pBsocnsible for the hanges in gene action, Basic pattern Por all cases, rerardicss of primary shenotype mene affected. @)e why was bosie pattern of sene beh vior so drasticea LLY wu many genes as a conger ucnce of an altevation at Pees: are of one che ™mesove? Oat condist ons were distrubed by this that alteved timing of mene action and for so many di Po ont genes? axtensive stud: of one s° stem of control oF gene action - The DS- Ac S¥SUcOM, a). wo elements, each disti nguisnable because of nn notroes each produces-- like any soe -callod sere mubtant-- control action of mene, b). Unlike the stationary genes -~ the DNA @arrving elements-- trese Glements do not remain in one »nositicns in the chro-osone commlement,. Can transvose from one location to another ing identity in process, Like senes but chanre baeir locations in the commlenente c)e Inheritance cen be followed as readily as any mutant, Linkares,y pos: tions in carcicse: 10S, CEC, vreansposition freauencic times and positions may be followed, d). Both elements can cause a change in the chrowosone - physical chens that may be observed, Like Phynchosciara - permant chanres,Class IT, ¢),. Transposition of Ds elen nt to locus of Imown mene -- cnanme in mene action results: 0 b CB =f. + + o. we to + 3 f), As long as Ac absent, c is a good recessive mutation, lio evicence of muvation to CO, As good as any known mutation in maice, e&). when Ac present -- mutations to C OCCU. Uceur at ces ain times in development and in certain cells, h). Control of time of mutation -~ depends on Ac, As a weole the nigner tne cose f Ac, tne later the time of occurrence of mut Controls pattern - wnen gene acts and in cells. ess = due to ch-nge in Ds element, not in genes at s soneti renoved waen cnange occurs, Wi). Becauce of teansposit’on, could set cases of Ds enébwing Bifferent kmown gene loci, Many obtained: C Sh Bzy wh 4A A Ba, S§ Sh B2y Wx l A, Bo U Chr.9 3: 5S 1 hh k}. The Alleles of Ac. and Ds. Different alleles (formerly called states) of both Ds and Ac can be recognized, bike alleles of known fenes in that tvey ave clear expressions but not related to one position in chr ~csome, -One allele of Ac? Pettern with all Ds mutants: Anke — axeedingly vrecise control, Very stable tyoe of ernression, fne ther allele - always produced cnanse of gene acticn in one rticular cell, Precise control of time and cdl in weich ehe mee would occur, VI, Investigation of another s*stem of elements -- Spm 1. History of detection: One of the early eo ses - luteus, yellow plant. chlororhyll.e a), lutation t-mes - many. One expression: Hecinrocal patterns: Sebo : 7 oak te? he ay ial? ” Sufa nr any ~ a 4 yt se / b). Inheritence behavior -- very confusing, ‘any chanees in plant to different expressions and controls. No clear cut inheritance behavior thet was readily analysible -- at that time, ce). In course of soudy == anpcarved anotner mutable in cultue mutasle lu -- A toa - mutable, Antnocranin in plant and kernel. ike ee Voor ¢ difficult to ecco~mrehend the sm rasvonsible, a). Study of a -m. uch chances in rene acu: sigh sbate of confusion, cr a O Ww B 3 2 ch 1 @ 3 eo) ° a i) i H VII. Ce . 3 * . ae s " e). In course of study of BouM, CPrOSS! Ay Ay XK ay D> — One kernel on ear = colorless with A_ spovws, Plant grown from it. Origin of a,™ Study of a,” - sirmle,. a). Assume clement entered Ay (evidence of this later), Chanre from A to a-m b) Mutations to A or alleles of A in presence of anotrcy element - ODM, ¢), Uriginal tyne of mutetion pattern produced br a4 -m Slide ae () }. Miesing kernel ~ apnnesrance. Slide (ie) © Sprl present = spots of A in colorless bacl:eround = karnel Streaks of A in green backsround - plant, Spr absent - deep color in kernel and plant. Gonstant in behavior, e). Spm = controls suppression of gene action and induces mutation, Mutants in germ line -- stable in system, some other f),/alleles of ap isolated.: Siia © © @)e Inhoritsnee of alleles: Combined: de (se) Al siide J) (D Slide G7 fr Same h). Allele of Spm - SPM-We seduced capacity for inhibiticn of gene action and for mutation: Plant colored - slowly. erynel colorless, few A specks ony. vocessive to Som=standard, Return to stud of Qorml, Prom wiich a =m arose, sane system? 1 m=] a). Found sane eenerasl system in sowe cultures of a4 and vory b). b). e). confused tyne of bennvior in others, Sori elenent present in the readily analysible cultures but did not is 1 oo KO OW What was present in obicrs, cS imto a =m of both types -- irmediatol+y introduced Spm from ag cul or Followed exactly that for ase clearcd up benunvi oO De a Bry a U Bo Proof of same spm element controlling mutations in both = aie *&5 or experiments, Whet abcut be! -- lons set xavier in aom cultuvs that were not analvsiole: ny? co f). Types of difficultics: Inheritance of variegaticn and expression 1 (1). Femele - colored, x ao® -- all kernels colored excent one op two -- make colortéss-backerotgd, few to “anny specks of color, Pollen = to ao - colorless beckground, many levee snots of color, (2). Hain ear on plant - no varieszation, Lillevs serrercated Gistinct ratios or peculiar vetios, (3) Two distinct classes of alleles. Sehavior diffs-ent VIIT, The solution of the a™ situetion: Q two classes of alleles of a.™@ The The Class I, Spm present = gene action turned on and off but no chanse in gene, When Spm absent or turned off A> ex -ression, Will peturn to this, Class ITI, In apsence of spm - pale color in plant and kemnel In presence of Spm = muitaticns to Ane Spm present -- its action crel&#e =» turned on and off in soples, Standard Spm - turned on in plant trreugnout grewth of “leant and formation of pametes = tur “f in some cells of endosperm, as 2 ™m vc, eo aa ry » * rea opm in an - cyele saifts: Off and on, lime of turnings off and on and time of mutation related, Sxample: Plant 7109B+1 Allele - Class IT Wx + / wx Spm hetrod of detecting presence of inactive Sym: 7 ‘Anke A yr SC baby were pu + “alge Hh: 1 Gehive 3 ~ “4A 6 b hae bo : * Wx + / wx Spm - active x a@ wx 1 Active Spm ; . : ‘ i a 2 "+ / wx Spm - inactive x rH on of Spm without chance in vosition, Proved cnangse in cvele act 4 ot seen in vleant or kernels, ie £ Froved oresence of inactive Sym when n YX, beaning of study == now heve know system - control of turning on and orf of pene action at svecifie tine and in specific cells = produces vooy specail patterns of cenavior of gene in ~lant and ke nel, Like Glass I chenre in Rhimnchosciara Same svstem can operate to control permanant chanves in gene acticn = like Vlass II of Rhynchosciara, Can get various t-pes cf control of sene action | of Spm to ang one trme -- like Standard Spm shab! Tizabi: ne - m . . . a? and a -- scowed seme be -svicr in dt... mt anu ero 2aneS of spm tenes from a control of seene action in bot Combiraticnae and permutations of alleles of two types of eontolling elements = can pet almost any time of comtrol of -one action divferentially in different tissucs of sane oreanisms. system of control of gene accion during develonment ma~ not be sco ak omplex to annreciate,