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THE EFFECTS OF UNEQUAL CROSSING OVER ATTHE BAR LOCUS I N DROSOPHILA'A. H. STURTEVANT

Colu?itbiaUlzizwsily, New York Ci tyReceived September 10, 1924TAB LE O F CONTENTS

PAGEINTRODUCTION. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Historical. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117Mutations and crossing over. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121Frequency of bar mutation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131The crossover values for forked, bar and fused. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132Facet number.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133Are mutations in general due to unequal crossing over?.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140"Presence and absence" and quantitative view of mutation. . . . . . . . . . . . . . . . . . . . . . . . . . . 143Are deficiencies due to unequal crossing over?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143Unequal crossing over and the exact nature of synapsis.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145SWYARY 145LITERATUREITED... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46

INTRODUCTIONIf one thinks of mutations as being simply inherited changes, it becomes

necessary to distinguish changes that involve whole chromosomes (e.g.,non-disjunction or tetraploidy), changes that involve several adjacentgenes (deficiencies and duplications), and what have been called "point-mutations" or "gene-mutations." Probably this last type includes quitediverse processes. I t is therefore important to collect information as to thenature of specific examples of mutation. For this purpose i t will commonlybe necessary to work with a frequently recurring mutat ion. Only onefrequently mutating gene has hitherto been discovered in Drosophila,namely, bar. Crossing over has proved to be the key to the mutationbehavior of bar, as will be shown in the present paper. The case appearsnot to be, strictly speaking, a point-mutation after all, but a new kind ofsection-mutation, in which the section concerned is so short as to includeonly a single known gene, and in which unequal crossing over furnishesthe mechanism for bringing about the new types.

H ISTOR ICALIn 1914TICE 1914) found a single male of Drosophila melanogasler that

had narrow eyes (see figures 1 and 2) . The new type, called bar (or "barred"Contribution from the CARNEGIENSTITUTIONF WASHINGTON.

GENETICS 0: 117 Mr 1925

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FIGURE .-Homozygous bar female.FIGURE .-Bar male.FIGURE .-Bar-over-round female.FIGURE .-Female homozygous for round, that was obtained by reversion.FIGURE .-Male that carries round, obtained by reversion.FIGURE .-Double-bar male.FIGURE .-Homozygous infrabar female.FIGURE .-Infrabar male.FIGURE .-Infrabar-over-round female.FIGURE 0.-Double-infrabar male.

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STURTEVANT,. H., UNEQUALROSSING OVER IN DROSOPHILA PLATE

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in the earlier literature), was found to depend on a sex-linked gene located at57.0 in the X chromosome. I t was further found that the bar character isdominant, in the sense that females carrying one bar gene have eyesdistinctly different from the wild-type or "round" eye (figure 3 ) . Becauseof this dominance the type has been extensively used in linkage experi-ments. MAY(1917) reported that the bar gene occasionally reverts tonormal (figures 4 and 5)-a process that has more recently been exten-sively studied by ZELEXY 1919, 1920, 1921). ZELENY ound tha t thefrequency of reversion is variable, but in many stocks is such that about1 in 1600 offspring from a pure bar stock receives a not-bar, or round,allelomorph. ZELENY lso concluded that the reversion probably occurschiefly (or perhaps exclusively) in females. His argument, based on thesex ratio found among reverted individuals, is not as convincing as thedirect tests that will be described in this paper, and which verify hisconclusion. ZELENY lso found that homozygous bar gives rise to a newand more extreme allelomorph of bar, that he has called "ultra-bar."For reasons that will be developed in this paper, I prefer to call i t "double-bar." The eyes of double-bar are distinctly smaller than those of bar(figure 6). ZELEKY as shown that the type is more strongly dominantover round than is bar, and also that double-bar is largely dominant overbar.

ZELENY ikewise found that homozygous double-bar stocks revert toround with a frequency not very different from that of homozygous barstocks, and that double-bar occasionally mutates to bar; that is. it cango all the way back to round a t one step, or it can give bar, which, in tu rn ,is capable of reverting to round. ZELENY as argued that the three types.round, bar, and double-bar, have the same characteristic properties,regardless of their origin. The round eye of reverted bar is indistinguish-able from wild-type; bar derived from double-bar does not differ from theoriginal bar, etc. This point will be considered in more detail in a latersection.

STURTEVANTnd MORGAN1923) showed that double-bar over bar2also gives rise to round-eyed individuals. They reported three reversionsfrom this combination and three from homozygous bar. In all cases themothers had been heterozygous for f ~ r k e d , ~hich lies 0.2 units to the left

In this paper the constitution of heterozygotes will be expressed as above in order to avoidcircumlocution or indefinitcness. "Double-bar over bar" is to be understood a s: "carryingdouble-bar in one X chromosome and bar in the other X chromosome."

3 Forked is a recessive bristle modification. Locus 56.8 in the X chromosome (we MORGANand BRIDGES916).

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UNEQUAL CROSSING OVER A T THE BAR LOCUS 121of bar, and for fused4 which lies 2.5 units to the right of bar. All sixreversions represented crossovers between forked and fused, though thetotal forked fused crossovers constituted less than 3 percent of the numberof individuals examined. STURTEVANTnd MORGANlso reported thatexperiments in which bar entered only through the males had failed togive any reversions, though no numerical da ta were reported. The presentpaper is based on the results of a more detailed study of the relationsfirst shown by STURTEVANTnd MORGAN1923).

MUTATIONS A N D CROSSING O V E RThe results from homozygous bar females, that were reported by STURTE-

+B j uV A N T and MORGAN,ere from females of the constitution -. A morefB+efficient type of experiment is that in which females of the constitution+B+- re mated to forked bar fused males. Table 1 (first row) shows thef Bfuresults obtained from an extensive series of this type. In the second rowof table 1 are given the results from mating a few females of the aboveconstitution to forked fused males.

TABLEB- X f B fu 3 (1st row ) or f fu 3 (2nd row) .f B f uTYPE OF YALE B ARUSED -----O---- 3

fBfu 5413 3749 94 140 5218 4160 93 124f f u 374 359 6 6 352 324 10 7To t a l . . . . . 5787 4108 100 146 5570 4484 103 131

I ROUND D OU B L E -BA R9 13

* In this and the following tables "0" signifies non-crossover classes; "1," classes resultingfrom crossing over in th e first region, etc.The mutant females that appeared in these experiments were, of course,all heterozygous for whichever allelomorph (bar or round) they receivedfrom their fathers, but in tables 1 to 18 this paternal gene is ignored and

the females classified according to the maternal gene. I n all doubtfulcases (including both double-bars), the classification was checked byraising offspring from the mutants, since there is sometimes difficulty inFused is a recessive venation character. It s locus is a t 59.5 in the X chromosome (seeMORGANnd BRIDGES916, LYNCH 919).

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classifying single individuals, a difficulty that can be removed by examina-tion of a series of specimens of a given constitution.

It will be observed that seven of the eight reversions, and also both ofthe double-bars, occurred in gametes that came from crossing over betweenforked and fused, though the total forked fused crossovers constitutedonly 2.4 percent of the population. The one exceptional case, a wild-typemale, is not above suspicion of having arisen through contaminationrather than reversion of bar. That he was really round-eyed was provenby tests. Only 4 other exceptions to the rule that mutation in this locusis accompanied by forked-fused crossing over have been met with in thework here reported. These will be discussed separately later.

On the basis of these results we may formulate the working hypothesisthat both reversion and the production of double-bar are due to unequal+.B +crossing over. If we suppose that, in a female -, crossing over occursfBfu

in such a way that the respective points of interchange lie to the left of thebar locus in one chromosome, but to the right of it in the other one, therewill result chromosomes of the constitution fBB+ and f f, , (or f+ and+BBf,). The hypothesis is that reverted round is simply no-bar, and thatdouble-bar is BB,-this being the reason for abandoning ZELENY'Same,ultra-bar.

This hypothesis makes reverted round and double-bar complementarycrossovers, and they should accordingly be prociuced with equal frequency.Table 1 agrees with ZELENY'S ore extensive data in showing that roundis apparently far more frequent than double-bar; but such a result was tobe expected for two reasons. Double-bar is not as viable as round, sothat fewer of the double-bar mutant individuals would be expected tosurvive; and double-bar is not always clearly distinguishable from bar,so that some mutant individuals are probably overlooked, while it is notlikely that any reversion is overlooked through difficulty of classification.

The double-bar over bar experiments reported by STTJRTEVANTndMORGAN1923) can be interpreted in the same way: the reversion ishere due to unequal crossing over just as in homozygous bar. I n the earliercultures of the experiments previously reported, only the reversions wereclassified for forked and for fused. Two of the reversions were in suchincompletely classified cultures. Table 2 , including all the double-barover bar data for which complete counts are available. contains one of thepreviously reported reversions and one new one. This table includesonly the male ofispring, since the BB derived from the fathers renderedthe classification of the females uncertain.

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UNEQUAL CROSSING OVER A T THE BAR LOCUS 123The process of unequal crossing over might be expected to give rise to

triple-bar from the females that are double-bar over bar. No individualthat could be so identified was obtained, though several specimens withvery small eyes were tested. All those tha t were fertile proved to bedouble-bar. Apparently triple-bar is either inviable or sterile. Thisproblem will be discussed again below.

TABLEB- x B B f " 3 .f B B f u

My own experiments with homozygous double-bar have not yieldedany mutations, probably because I have found this type hard to breedand have therefore not obtained large numbers of offspring. It may berecalled that ZELENYhas obtained both bar and round from such females,but not in experiments in which forked and fused were present. I n table 3 ,showing the data I have obtained, only males are recorded, for the samereason as in table 2, and also because the females could not be classifiedfor fused.

ROUND $

---- f2

TABLE-B B 9 X J B B $.BB fu

TOTAL

6809

B O R B B ~

0--+ I // "--

3933 1 2741

I n the case of double-bar over round, bar should be produced by anycrossover between the two bars of the double-bar chromosome. Thisevent might seem less unlikely to occur than the type of unequal crossingover invoked in the preceding experiments; and both of the chromosomesresulting from such crossing over should yield bar, whereas in the precedingcases, a given crossing over must always have yielded chromosomesbearing two different kinds of bar allelomorphs. I t is accordingly inGENETICS 0: MI 925

--1---

f--2 1 73TOTAL

BB 13

f" f +627 1 956 37 1644

----a 0 --1

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agreement with the hypothesis that tables 1 ant1 5 show a higher pcr-centage of mutation than d o tables 1 and 2. Two non-disjunctionalindividuals ia f:f,,gand a + + + Q ) have hem omitted from table 5 ..f RRfu

BB- X f " d l .f f uD O U B L E - B 4 R A N D R 0 I l . W i

, BA R0 1

P

No mutations are to be expected from females that are heterozygousfor bar and for round , since crossing over can not produce any new(4)combination. The results of the tests are shown in tables 6 and 7 , andare in agreement with this expectation. One non-tlisjunctional femalr(*) was also produced in this series.'

DO1:BI.E-BAR AN D ROUN D------ - - B i R

S E X 1 0 1 2 ! I, TOTaL / I---+ J I B / I n / ] . ! I J u ~ J-- -- -- -.- - - --- _ _ _ _ _ _ / /____.P 464 392 894 1 00 1 1 14406 1 0 ; 0 6 1I~ .. - -L. V. MORGAN1922 ) has described a race of D. melunogaster in which

the two X chromosomes of the female are attached t o each other, so th atsuch a female gives 100 percent non-disjunction. This race, and othersThis series also produced one female tha t was wild-type in appearance. Such a female would

be ei ther a double crossover-which is not at all probable in such a short chromosome section,or a non-crossover reversion of bar. This female was mated to an unrelated bar male, and pro-duced 124 bar-over-round daughters and 96 round-eyed sons; bu t none of the sons showedeither forked or fused. This result must mean that the exceptional female was due t o contamina-tion.

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U N EQ U A L C R O S S I N G O V ER A T TH E BAR LOCUS 125separate in origin but having the same peculiarity of attached X's, havebeen used to test the mutability of bar in the male. If a round-eyed femalewith attached X's is crossed to a bar male, all the sons get their X chromo-somes from the bar father and accordingly furnish a direct test of the

TABLE6-OXff" 3.fBfU--p- - -BAR

SEX I 1 1 2 TOTAL

mutability of bar in males.6 A total of 10,079 bar males has been observedfrom such matings, with no rounds or double-bars. There was, however,one other male that had an eye intermediate between bar and round.This new type, called infrabar (figures 7,8,9) has been shown to representa new allelomorph of bar. I ts somatic appearance will be described inmore detail later in this paper.

TABLEB- Xff" 3 .

f f u

I BARSEX 0 I 1 I 2 --I m'

Tests soon showed that infrabar behaved as a single unit in inheritance.Bar can not be recovered from it, and i t shows the samelinkage relationsas bar. The convincing proof that i t represents a modification of the bargene will appear below.Homozygous infrabar behaves like bar in that i t reverts to normal, andalso produces a new and more extreme type, double-infrabar (figure lo),

6 Occasionally the attached X 's sep arate, and a regular son carrying a maternal X i s produced.I n the pres ent series of exp erimen ts this source of error was eliminated by hav ing the two m aternalX's differ from th e paternal one in a t least one other mu tan t gene besides bar.

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126 A. H. STURTEVAKT

analogous to double-bar. As shown in table 8, both these events are againassociated with forked-fused crossing over.

Of the three double-infrabar individuals, one was sterile, and one wasaccidentally lost, but the constitution of the other was established bybreeding tests. The type was also obtained in another experiment; andits appearance and mutation behavior will be described later. This seriesshows the same excess of rounds over double forms as did the bar series,and the explanation is doubtless the same. The difficulty of separationis even greater here, owing to a greater variability in eye size (see below).

I N F R \ B A R / ROUND B ~ B ~0 1

Total jJ" 1 f fu lI i - 1

i 4607 3606 94 1 142 8449 0 5 )-0 13 1 4341 1 3905 ( 97 106 8449 1! i 2 ' 1 1 / 2 1 0Bar-over-infrabar females of three different constitutions have beentested. They have produced rounds, and also a new double type that had

eyes only very slightly larger than those of double-bar. These mustevidently have bar and infrabar in the same chromosomc. Tables 9,10 and11 show these results. I n most cases the fathers of these cultures did not

f B~- X various 8 3 .B f u

B A R A N D I N F B A B A B M A L ES 1 D O U B L E TYPE

carry fused; for this reason the females, among which no mutants weredetected, are not listed. The forked fused mutant male was sterile, bu t theconstitution of the other was tested. All the experiments here described,on "bar-infrabar" (figure lo), concern this mutant gene. The stability ofthis new type in the male has also been tested. Matings of bar-infrabarmales to attached-X females (also differing in a t least one other sex-linked

0---A-fu I f

1 c?1 Toll,+ I I J u I I + I f l u

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UNE()UAI, CROSSING OVEK AT THE BAR LOCUS 127gene) ha ve produce d 9042 non-disjun ctional sons,-all of them bar-infrabar.

TABLE0

SEX

B A R A N D I N F B A B A R -- I0 1 I -1 MUTANTS

T he doub le-type male of tab le 11, which resembled those from table 9,was tested. H is descendants are discussed below und er the nam e "infrabar-bar."

-+497505

--J Ju--415476

These new double types have made i t possible to devise crucial tests

---Ju1015

SEX

0d

of th e th eor y of unequ al crossing over, which m ay now be described.

Total

9401012

f1816

T h e first test m ade was th at of bar-infrabar over round. Tables 12 and13 show the resul ts obtained. I n add it ion one culture of this series gavetwo w ild-type females, one in th e first count and anoth er in the la st cou nt ,

00I

B AR A N D I N F R A B A R

SEX---8

D O U B L ET Y P E

----- --J---01

R O U N D- --Ju01+24452365 - - -----f--10Total-7814847/ f u-2032347 -- -----' B A R -I N F R A B A R A N D R O U N D

/u-964BA R

/Ju-

--J7471

l N P R A B A R

+1

1 1

---

fu303321

Total

723641

f B B ~

394308

-------

BB{40

--2

f j ,02

+----47 --/BB"/,83

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ten clays 1,tter. 'I'hcse fem ales give rise to th e sa m e difiiculties a:, t l i c l thcwild-type obtained in the series reported in table 7. On e of t he m wastested, and gave unexpected resul t s . The mother had carr ied vermi l ionin he r fo rked fused X , an d th e father had also been vermilion forked fused.The tested exceptional iemale was found to carry one wild-type X anclone forked fused S , bu t d id not carry vermil ion a t a ll . Under the c i rcum-stances i t is open to quest ion whether these two exceptional individualswere no t due to contam inat ion . T he y wil l be discussed again late r .

BB"- X f j U 3.j .f"I iB A R - I h T R A B A R A X D R O U N D / B A R I I N F E A P I R

Tables 1 2 an d 13 show t h a t bar and infrabar can bo th be recoveredfrom bar- infrabar . I t appears then th a t in the double form the individuale lements mainta in the i r ident i ty . Ev en more im po rtant , however, i s theindicat ion t h at they m aintain their sequence in the chromosome. ,4sshown in table 9, the bar-infrabar f i rst came from the combinat ionf R i-, as a not-forked not-fused male. If th e two eleme nts of d oub le form sBfuar e arranged in the same l inear series as the rest of th e genes, this resu l tmu st m ean t ha t the bar now lies to the le f t of th e infrabar . Th is supposi -t ion i s ent i re ly borne out by tables 1 2 an d 13, which are ex per imen ts ofth e usual typ e used to establish sequence of genes. All th e 9 single typesrecovered agree with th e suppo sed sequence.

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Bar-infrabar has also been tested against infrabar (table 14).Here again there is an opportunity for the production of a triple form,-

but since the corresponding round did not appear, its absence is not signi-ficant. The one double-infrabar confirms the sequence of the componentparts of bar-infrabar. I t was tested, and all the results from double-infrabar reported below were obtained from flies descended from it.

Examination of the data in table 11 shows that the double form obtainedthere must have had infrabar to the left of bar; that is, i t was infrabar-barinstead of bar-infrabar. The tests made with i t appear in table 15.

SEX

08'

These results show, in fact , that the sequence is infrabar-bar as supposed.Except for this difference the mating is the same as in table 12. I t will be

IN F R A BA R

f f "-otalINFRABAR-BAR AND ROUNDobserved that the two not-forked not-fused single types in that tablewere both infrabar, while the two obtained here were bar; the one forked

BA R

+

fused there was bar, here it was infrabar. There is a total of 13 single-typemutants in tables 12 to 15, all of them agreeing in indicating that the two

- --- 2elements of double types maintain not only their individuality but their

-- --1

fu483478

+1517

sequence.

B ~ BB % B469408

/ B ' B / ,1515

The double-infrabar obtained in table 14 has been tested against round(tables 16 and 17).

f f ,-----1

1 9

SEX

03

B i g i A X D R O U N D / ~i-0

h538574

1 2Total -11981101

----/ ~ i ~ i-----29505 -i g ;11 +1213 +02-- f f u11 f B ~ B ~ ~ ~177

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The results in these tables show that double-infrabar was correctlyidentified, and that it behaves as was to be expected, giving infrabar byboth kinds of crossing over,-just as double-bar gives bar in both cases.

Double-infrabar over infrabar has also been tested, in the hope ofobtaining triple-infrabar (table 18).

No triple-infrabar was detected; but its absence is not surprising, sincethe corresponding round occurred only once, and since i t is not a t all surethat the triple form could be distinguished from the double one.

IDOUBLE I N F RABAR AND I N F R . ~ H A R * 1 ROUND

SLY 1 0 1--- II___-___ I Totd 1/ + i f l u I A' i f I

Q 851 I 777 2.5 31 18' 665 750 26 29 1470 01

* The double-infrabar and infrabar flies are not entered separately. In the original countsthey were separated; but the classification is uncertain at times.

One further type of female was tested, namely, bar-infrabar overinfrabar-bar (table 19).

The one mutant infrabar obtained in the series is in agreement withthe sequence in which bar and infrabar were supposed to lie in the twoX chromosomes of the mother; and this mutant is also the only one yetobtained from a mother carrying a double-type allelomorph in each X,where forked and fused were heterozygous. I t therefore serves to completethe demonstration of the relation of crossing over (between forked andfused) to mutation in the bar locus.

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 131The experiment of table 19 was, however, planned for another purpose.B B "I t will be seen that in the mother, which was- qual crossing overB ~ B '

might give rise to new types, namely, double-bar and double-infrabar.

0 1 0 1-- -- --- --- -- Total+ f fu fu f + flu fu f--- ---* . . . . . . . . 95 74 3 4 1762 428 335 8 15 341 319 7 16 1469* Females not counted in the mating to BiBmale.The first could not be distinguished, in somatic appearance, from theunmutated double types (BBi and BiB); but the double-infrabar shouldbe readily detected. Such an individual would be forked. I t may accord-ingly be concluded that none of the 35 forked (not-fused) offspring repre-sented equal crossing over between the halves of the two double-type barallelomorphs present. I t therefore seems probable that crossing over ofthis kind is not much, if any, more frequent than is tha t between the twoelements of a double-type allelomorph when the other chromosome carriesround (tables 4, 5, 12, 13, 15, 16).

Several of the above tables agree with a small series of infrabar overround, heterozygous for forked and for fused, in showing that infrabarlies between forked and fused. It must clearly be either an allelomorph ofbar, or bar plus a modifier that lies near bar.

The experiments with bar-infrabar and with infrabar-bar show thatthese two types both contain infrabar as a unit distinct from bar.

Since bar-infrabar was produced by an unequal crossover that occurredvery close to the left of infrabar, i t becomes unlikely that a modifier canlie on that side of the bax locus; infrabar-bar furnishes similar evidencethat there is no modifier to the right. All the evidence thus indicatesclearly that the infrabar gene is really a modification of the bar gene itself.

F R E Q U E N C Y O F BAR M U T A T I O N SThe data presented in tables 1 to 19 have been examined in an attempt

to formulate some general statements as to the relative frequency of theGENETICS0: M I 1925

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various tyl)cs of mu tat ion in the bar locus . I t i s probal) le th a t homozygou\double types, and double over s ingle show the lowest frequencies ofmu ta t ion , and th a t double typ e over round shows the h ighest . Boththese results might ha ve been expected. Th ere is , however. so muchvariability am on g crosses of t he sam e general na tu re t h a t these conclusionsm ust be accepted with caution. Fo r example, the two largest series arc.those from homozygous bar (20,438 offspring) an d from h oi no zy go u~infrabar (1 6,9t 8 off spring). T h e mechanical con ditions should be alikein the two cases, s ince bo th represent homozygous s ingle type s. Y ctfrom th e first the re ap pe are d0 .03 pe rce nt of reversions, or 1 in each 2020offspring; from th e second there were 0.11 percent , or 1 in 940 offspring.I n view of such unexplained differences as this, an d in view of th e statis ti-cal difficulty of determ ining pro bable errors for such small percen tages,i t does no t seem profitable to discuss fur the r this aspect of th e d at a , exceptto note th a t mu tat ion f requency does no t appear to be corre lated wi thfrequency of forked-fused crossing over.

THE C R O S S O V E R VALUES FOR FORKED, BA R A N D PUSEL)The experiments recorded in tables 1 to 19 include by far the largest

series of d a ta ye t accum ulated for the crossover values of th e thr ee loci,forked, bar and fused. These are summarized in tables 20 and 21. Inthese tables a ll the m ut an t individuals have been omit ted. Their inc lus ionwould n ot hav e affected an y of the values appreciably. I n table 22 the

f B f. crossing over.CROSSOVERS

TYPE OF FEUALE TESTED I NON-CRO>SU\rERS TOTAL/ - - - & r l - - - ' Keyion 2 ,ISingle type over round I18 185 1 7,396Double type over round 52 1 603 23,592Double type over single 12 1 90 i 3,381i ITotal. . . . . . . . . . . . . . . . 33,409 , 82 878 34,369Percentage. . . . . . . . . . 97.21 0.24 1 2.55i I

da ta a l ready publ ished on these loci are included wi th the above, in orderto arriv e a t final "m ap values" for the thre e loci.On t he basis of these da ta , i t seems best t o m ap forked 0.2 uni t to theleft of ba r, t h at is , a t 56.8; an d fused 2.5 units t o th e r ight of ba r, at 59.5.thu s m aking the forked-fused interval 2.7 uni ts .

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UNEQUAL CKOSSING OVEK AT 1'HE BAR LOCUS 133FACET NUMBER

I t has been shown by ZELENY nd MATTOON1915), M A Y 1917) andZELE NY 1922) th a t selection for num ber of facets is effective in isolatinglines of b ar flies with high facet n um be rs or with low. Th ou gh no detailedgenetic analysis has yet been reported, there is abundant' evidence in

TABLE21f f, nossing over.

T Y PE OF FE M A L E T E S T E D / NON-CROSSOVERS I CROSSOVERS I TOTAL. . .ingle type over single. 48,966Double type over single. . . 9,717Double type over double. . 3,175 -Total. . . . . . . . . . . . . . . . . . . 61,858Percentage.. . . . . . . . . . . . . . 97.40

these papers th a t ordina ry ba r stocks are heterogeneous for modifiers (n otin th e bar locus) tha t affect facet num ber. This is also th e impression Ihave gained from extensive but less exact studies, with numerouscrosses involving bar.TABLE 2

Tolal linkage data.

1 Total 1 9 5 1 3 7 , 0 5 5 / 0.26WEINSTEIN 918 1 20 "29" 2.4able 21 63, 508 2.6

LOCI

fB

--otal "lxirnary" data 1 1850 1 71,806 1 2.58SOURCE OF DATA-ORGANnd BRIDGES 916BRIDGES 917Table 20

MORGANnd BRIDGES 916 1,201Table 20 1 9 1 34,369 I i::

P E R C E N T-0.50.50.2

CROSSOVERS-8582

TOTAL-1,70698034,369

Bfu

GENETICS10 : MI 1925

Grand totalMORGANnd BRIDGES 916BRIDGES917Table 20Total

2847

222468781146

107,376

8,7681,40134,36944,538

2.65

2.53.32.52.57

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Ano ther source of variabi l i ty in facet num ber is tem peratu re. I t wasshown b y SEYSTER1919) th a t h igh temp era ture decreases the face t nu m-ber of bar , and th is re la t ion has been s tud ied in grea t de ta i l by KRAFKA(1920), ZELENY 1923), A. H. HERSH1924) and K . K. HERSH1924).These observers hav e shown th a t the effec t i s present , thou gh in varyingdegree, in double-bar, round, and in various heterozygotes, as well as inbar . Al though these s tudies furnish essent ia l da t a for any comple teana lysis of th e mod e of ac tion of t h e ba r series of allelomo rphs up ondevelopment, they need not be further discussed here.

T h e evidence just reviewed indicated t h at i t would be necessary toget sto cks as nearly uniform for modifiers a s possible , an d also to controlthe tempera ture , i f any re l iable d a t a were to b e collec ted as to the re la t iveeffectiveness on facet-nu mb er of t h e various com bination s of b ar an di n fr a bar . Ac co rd ingly , a f en la le t h a t w a s f s ' was mated to a round-eyed~BB 'vermi lion fem ale f rom vermi lion s tock. T h e descendants f rom this m at ingwere inbred (brother-sister pair matings) for seven generat ions. I n eachgenerat ion a female heterozygous for two of the three ba r al lelomorphsconcerned was m ated to a male carrying the third al lelomorph. T h e l inewas m ade homozygous for forked; b u t both vermi lion an d fus ed wereel iminated. N o other selection was practiced. A female of th e third inbr edgenera tion was mated to a n infrabar male , and a d aughter th a t was infra-bar over round was mated to a male f rom the four th genera tion. Fo rthree more generat ions the infrabar series was crossed to the inbred l ine.After the eighth generat ion the pedigrees are somewhat more complex,but as close inbreeding as was compatible with maintaining four al lelo-morphic sex-linked genes was continued for six more generations beforethe face t counts were begun. T h e other types s tudied (bar- infrabar ,reverted bar, e tc .) were al l crossed to the inbred stock just described, atleast f ive times (most ly using females t o allow crossing ov er a nd get a sm uc h of t he X's uniform a s possible) before being used in th e co un ts.Th is procedure should have resulted in m aking th e var ious s tock s prac t i -cal ly al ike with respect to modifying genes. and the resul ts obtainedare sufficient ly consistent to indicate that there was no heterogeneity inmajor modifiers, thoug h i t is st i l l possible t o interp ret some of the minortli iferences observed as being du e t o unelim inated divers ity in modifiers.

be riv ed from the experim ents of table 1, s o t h a t t h e BB of t h e following discussion is knownlo h a w com e from the BB male of th a t tab le , and to have been der ived from homozygous barby forked-fused crossing wer .

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 135The temperature control used was not very exact, but maximum-minimum daily records show that 25C was maintained to within about

& 1C, and even these deviations were probably of short duration. For themain body of the experiments it has not proved possible to detect anysystematic effect of the fluctuations in temperature that did occur. Thefew experiments in which such an effect is perhaps present will be specifiedwhen described.The facets of the smaller eyes,-up to and including homozygous bar,-were counted directly under the binocular microscope, usually on etherizedflies, but in some cases on alcoholic specimens. The eyes larger than thiswere not found to be workable by this method. Such specimens were killedand cleared in KOH. The surface of each eye was then removed andmounted on a slide. By the aid of a camera lucida a drawing was made,representing each facet by a dot, and these dots were then counted, eachdot being marked by a check as counted. I n all cases the right eye alonewas used.The main series of data is shown in table 23.The table shows that homozygous infrabar is about like bar over roundin facet number, but the two types can be separated by a pecdiaritycommon to all the larger infrabar and double-infrabar types, namely, aroughened appearance of the eye, due to irregularities in the rows offacets. This peculiarity is not present in bar eyes, and is almost completelyrecessive in bar over infrabar. I n infrabar over round (which is not farfrom round in facet number) the roughness is variable in extent, and maybe not a t all evident,-in which case the type can not be distinguishedwith certainty from homozygous round. I n other stocks, where themodifiers are different, it often happens that infrabar over round isregularly conspicuously roughened and is easily distinguishable fromround. This roughness of the eyes may be taken as evidence that theinfrabar gene is qualitatively different from bar, rather than being merelya fraction of bar.

The table shows that in general when bar and infrabar are both presentin an individual, the infrabar produces almost as great an effect in reducingfacet number as would another bar, though in the absence of bar the

B B Binfrabar is far less effective. For example,- 68, - 348; but- =74.B B" B"And in general, BBi is practically as effective asBB throughout the table.In two cases the observed differences, though surely not significant,indicate that BBi is more effective than BB (that is, the combinations

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136 A. 11. S T U R T E Y A N Twith BB and wi th B " . Similar relat ions are shown in other p ar ts of th etable .

TABLE3Fnret nzmzbers of Pies iar ryi ng variozis comb natiorz~ J bar al le lov~o rphs.

T h e most s t r ik ing re lat ion shown by table 23 is th a t th e relat ive posi t ionof identical genes affects their action on facet num ber. Th ere ar e threesimilar comparisons to be made:

B BB- = 68.1 versus - = 45.4B +B BB-= 73.5 versus- 50.5B +B B"B"- 292.68 versus- 200.2B +

B8 This value for- s different fro m the one of t ab le 23 . I t is based on a series reared a t theB1

~ " isame t ime as the- ith which i t is here compared. Th e difference between this value and t ha t-4-of the table is probably due t o temperature.

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UNEQUAL CROSSING OVER AT THE BA R LOCUS 137Since the bar allelomorphs are to be thought of as inhibitors of facet

development, it will be seen that this comparison indicates that two barallelomorphs l yin g in the same chromosome are more ejective than are thesame two allelomorphs whe n they lie in opposite chromosomes.

Such an unexpected result must of course be checked up carefully.Only two possibilities of avoiding the above conclusion seem open. Theresults are due to (1) accidental differences in temperature or modifiers;or (2) the round allelomorph of bar brings about a reduction in facetnumber just as does bar. Both of these possibilities can be eliminated, asthe following paragraphs will show.

There is no temperature effect, since in each case the cultures wereB BBreared side by side; and in the case of - ersus -, several different testsB +

all gave the same type of result.If the results are due to accidental modifiers it is scarcely conceivabletha t these should lie anywhere but near the bar locus, because of theinbreeding to which the stocks have been subjected. As will be shown

below, another bar chromosome (derived by mutation from the inbred BBof this strain) has been found to give results sufficiently close to the barused here so that the conclusions as to the effect of position must apply alsoto the new bar. And two other not-bar ("round") chromosomes have beenfound to give substantially the same result as the one employed here (seebelow). These facts eliminate the possibility of explaining the result asdue to accidental genetic or environmental differences.

The second possible escape from the conclusion as to the effect ofposition lies in the assumption of an effect produced by the round allelo-morph. This has been tested by determining the effect on facet number ofreverted bar and reverted infrabar. Round obtained by reversion fromhomozygous bar or infrabar stocks cannot carry a normal allelomorphon the view advanced in this paper, unless such an allelomorph is alreadypresent in the parent stocks. But such a gene is, almost by definition, notan allelomorph of bar; and in any case cannot be supposed to produce the

B BBeffects here under discussion, since the - and the- ould both carry it.B +Two different rounds by reversion have been introduced into the inbredstocks, by the same method as used for BB%nd BiB< Care was takennever to use flies carrying one of these reverted rounds in the same culturewith the old round of the inbred stock, so that i t is certain tha t these newrounds are really due to reversion,-if not from the supposed source,then from some of the allelomorphs within the inbred stock, since a new

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reversion may have occurred during the process of gett ing the desiredmodifiers in to the rever ted round s tocks. One of the rev er ted rounds,called "rev. B ," cam e from th e hom ozygous bar experim ents of tab le 1 ;the other, cal led "rev. B7," ame from the homozygous infrahar esperi-m en ts of tab le 8. T h e resul ts of these tests are shown in table 21 .

TABLE41;acef ( o w n i s t o t e s t ltntrrre of reuersio~ls.

- - . -~I CHROUO5OYP TESTED AC..ZINhT1I BH I B B ~ I T ci .e . ,c?),--- _ _ . - - - - . - I _ _ -.-I____ __

Wild-type (control) ( 45.42 1 . 2 4 I 50.46+ .40 1 7 3 8 .8 j ~6 .5Rev. U . . . . . . . . . . . . 45.631- .45I i 4 5 . 4 8 ~ 1 1 1 . . . . . . . . . .~ e v . i. . . . . . . . . . 43.92 1- .26 , 46.132.36 704.4k8.0

Th ese d at a suggest th at the reversions,-especially th e mo re thoro ugh lytested one from infrabar,-may give sl ight ly smaller eyes th a n does th ewild-type allelomorph. Certainly they do no t give larger eyes. An d st i l lmore certainly, with B.B or B.Bt they do no t g ive as la rge eyes as do th e

6: ncorresponding types - n d -. These d a ta el iminate th e second possibleB B zm eth od of ex plaining awa y the effect of t he position of th e b ar a llelom orp hs

on face t number . T h e conclusion mu st s tan d as s ta ted on p . 137.It seems prob able t h a t such an influence of th e relative position of g enes

on their effect iveness in development may be interpreted in terms ofdiffusion an d localized regions of ac tiv ity in th e cell. Th is idea is, however ,scarcely wo rth e labora ting unt i l more evidence i s obta ined. I t m ay ,however, be pointed ou t th a t there is another possible applicat ion of th ehypothesis of a position effect.I t ha s bee n shown by BRIDGE S 1921) tha t in t r ip loid individuals therecessive genes brown, p lexus a nd speck do n ot become dom inan t to the i rnormal al lelomorphs even when two recessive al lelomorphs and onedo m inan t a re present . Unpubl ished d a t a collec ted by BRIDGES in p ar tverified in an independently arisen series of triploids in my own experi-ments) show th a t th is re la t ion i s a genera l one for a l le lomorphs tha t d ono t produce a n obviously in termedia te d iploid he terozygote . B u t BRIDGES(BRIDGES nd MORGAK 923) has shown that a different relat ion mayoccur, even for some of the sam e genes t h a t show th e former relat ion i ntr iploids. I n the example referred to, a port ion of the second chromos ome,carry ing the nor ma l al lelomorph of plexus (am ong oth er genes) ha s becomeat tach ed to a chromosome 111. It is possible, the refore, to ob tai n indivicl-

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 139uals with two complete second chromosomes, each of these carrying theplexus gene, while a normal allelomorph of plexus is present in the sectionattached to a chromosome 111. Such individuals are plexus in appearance,-not as extreme as those in a pure plexus stock, but far more like such astock than like the ordinary triploids carrying two plexus and one not-plexus allelomorphs. While it is possible that the difference here is due to adifferent "balance" of modifying genes in the extra section of chromosome11,i t seems likely that the effective agent is a difference in position. It isto be remembered that in Drosophila the homologous chromosomes lieclosely apposed in somatic divisions (see METZ 1916), so that there isprobably a real difference in relative positions in the two cases.

Besides the comparison of round (ultimately from vermilion stock)with round obtained by reversion from bar and from infrabar, two otherderived types have been compared (as to facet number) with' the corre-sponding original types.

An infrabar from bar-infrabar over round (table 13) was introduced intothe inbred strain by six successive backcrosses, and was then comparedwith the old inbred infrabar, both types being made heterozygous foidouble-bar. The control (old infrabar) value is rather lower than thevalue given in table 23, probably because the temperature ran slightlyhigher.

Since the difference between the two means is about 4.5 times i ts ownprobable error, it is probably significant, but more extensive data will berequired to establish this point.

A female of the inbred series that was double-bar over round, matedto a round male, gave rise to one bar male by mutation. This male wasmated to double-bar-over-round females, and the resulting double-bar-over-bar daughters were compared with double-bar over the old inbredbar, derived from cultures made up a t the same time and put side by side.Here again there is a slight difference from the value of table 23, perhapsdue to a temperature difference.

The difference between the means is slightly over 3 times its probableerror, and may be considered as doubtfully significant. Here again, moredata are needed.It may be pointed out that in tables 25 and 26 the derived type ispresumably the larger in both cases. I t is possible that this result is to becorrelated with that recorded in table 24, namely, that round by reversionis perhaps smaller than wild-type. Both relations are consistent with theview that there exists a normal allelomorph of bar that has an effect onfacet number opposite to, but much weaker than, tha t of bar; for bothGENETICS0: MI 1925

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140 A. H. STURTEVANTof the derived single types tested were from double type over round, sothat these derived forms may really be single type plus normal allelo-morph. This possibility requires further experimental investigation.

TABLE5BBFacet counts jrom F .

1 DIFFERENCE OFMEANS

TABLE6 BBFacet counts jrom -.B

Old B'. . . . . . . . . 3 4 . 7 3 + .3 5 3 . 2 4 k . 2 4New B ~ .. . . . . . 3 6 . 7 9 k . 3 1 2 . 7 6 r t . 2 2 2 . 0 5 k . 4 6

ARE MUTATIONS IN GENERAL DUE TO UNEQUAL CROSSING OVER ?

Old BNew B . . . . . . . . .

One of the first problems raised by the discovery of the nature of barreversion is as to how widespread may be the phenomenon of unequalcrossing over. One direct test has been attempted, making use of MUL-LER'S method of testing for the frequency of occurrence of new lethalmutations. Females were made up that carried one wild-type X chromo-some and one X with the mutant genes scute (locus 0.0), echinus (5.9,crossveinless (13.7), cut (20.0), vermilion (33.0), garnet (44.4), and forked(56.8). Such females were mated to males carrying all the mutant genesnamed. I n such matings it is possible to detect practically all the crossing

NUMBER

3 130

over that occurs in the X chromosome, except that to the right of forked(about 13 units). Counts were made from individual females, in order tomake sure that they carried no lethals. Forty-one wild-type daughters(non-crossovers) were tested from such matings, to see if the non-crossoverX chromosomes carried new lethals. The only lethal that occurred wasin a paternal (i.e., scute echinus crossveinless cut vermilion garnet forked)chromosome. Thirty-eight double-crossover daughters and one triple-crossover (i.e., a total of 79 crossings over) were also tested; and again nolethds occurred in any of the maternally derived chromosomes, thoughthere Rae two doubtful cases of new lethals in the chromosomes derivedfrom the dt iple-recessive fathers. While this experiment was done on a

MEAN---3 . 1 0 k . 3 3

3 4 . 8 7 + . 4 5

U

2 . 7 6 k . 2 4

DIFFERENCE OFMEANS

3 . 6 5 5 . 3 2 1 . 7 7 k . 5 6I

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 141

small scale, it furnishes no indication that crossover chromosomes aremore likely to contain new lethals than are non-crossovers.

There is, however, another kind of evidence that argues against anygeneral applicability of the unequal-crossing-over explanation of mutation,namely, the cases in which mutations can be shown to have occurred inthe X chromosomes of males, since it may be taken as established tha tcrossing over does not occur between the X and the Y of a male.

We have seen earlier in this paper that infrabar arose from bar in amale, and that its later behavior was not in agreement with the view thati t represented a quantitative change in the bar gene, as it should if due tounequal crossing over. I have also obtained yellow, a fused allelomorph,and a lozenge allelomorph under the same circumstances, namely, frommothers with attached X's and in experiments where known sex-linkedgenes were present, so that breaking apart of the attached X's was knownnot to have occurred.

Unpublished data are available for 5 other cases of the same sort,either from attached-X or from "high-non-disjunction" mothers, asfollows: rudimentary (C. B. BRIDGES),a dusky allelomorph (C. B.BRIDGES), sable allelomorph (E. M. WALLACE),hite (L. V. MORGAN),and a new lozenge allelomorph from lozenge (C. B. BRIDGES). In dl ofthese cases, as in that of infrabar, the mutant type first appeared as asingle male.

MULLER 1920) reported the occurrence of white as a "somatic"mutation in a male. From a stock in which white was not present heobtained a male with one wild-type eye and one white eye. This male alsotransmitted white to some (all that were tested) of his daughters. I n the-same paper MULLER escribed briefly a mosaic male that was pay'&-yellow, and transmitted the new character to his offspring. Dwtor-BRIDGESnforms me that he has a similar (unpublished) record for yellow.MOHR(1923 a) reports a similar case for a singed allelomorph, though,here some of the X-bearing sperms carried singed, while others did not.-I have observed two other such cases,-both in D. simulans. The mu&pt.types dusky and fused (both corresponding to the types of tJwwmnames in D. melanogaster) each appeared first in an individual that showedthe new character in only one wing; and in each case tests showed thatsome of the X-bearing sperms carried the new gene, while others did not,In all cases discussed in the last two paragraphs, genetic tests haveestablished the allelomorphism of the new mutant genes to the old oneswhose names they bear.

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142 A. H. STURTEVANT

There is thus clear evidence that mutations have arisen in the followingsex-linked loci in the germ-cells of males: yellow (3 times), white (twice),lozenge (twice), dusky (twice), fused (twice), singed (once), bar (once).It should be noted that all these loci are among the more mutable ones ofDrosophila.

Another class of cases to which the unequal-crossing-over hypothesisis probably not applicable is that in which mutation can be shown to haveoccurred a t some stage other than maturation. A number of such in-stances are on record for Drosophila. The mosaic males described aboveare examples, and a longer list of cases for autosomal mutant types andfor sex-linked mutations in females could easily be compiled. But sincethere is evidence that crossing over does very rarely occur a t somaticdivisions, this evidence can hardly be considered decisive. In the case ofcertain types of frequently recurring somatic mutations in plants, how-ever, the mutation occurs far too often to make an appeal to somaticcrossing over seem plausible. The clearest example of this sort is thevariegated pericarp of maize studied by EMERSON1917) and others, inwhich a given gene mutates many separate times in a single individualplant.

Mutations are known in which there appeared to be no crossing overin the region concerned,-both in females and in males where crossing overdoes not normally occur a t all. The previously cited cases of mutationsin the X chromosomes of males are examples. These may seem to furnishconclusive evidence that mutation need not be accompanied by crossingover. There is, however, one possibility that needs to be considered in thisconnection.

Recent results (not yet published, but soon to appear) obtained withtriploid females (BRIDGES nd ANDERSON) nd with females havingunlike attached X's (ANDERSON,. V. MORGAN,nd STURTEVANT)aveshown that crossing over must normally occur when the homologous chro-mosomes are doubled: that is, in a "four-strand stage" (in diploid females).These results show also that crossing over may occur between only twoof the strands a t a given level. Now, if it be supposed that sister strandsmay cross over with each other, there will result chromosomes in which norearrangement of mutant genes has occurred, since sister strands comefrom the division of one chromosome and will be identical in the genesth at they carry. Yet i t is conceivable th at such crossing over might beunequal, and in such a case might lead to the production of a new mutationthat did not appear to be due to crossing over.

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 143The data presented in this paper show that such an event must be

extremely rare in the case of bar, since no clear case was found of barmutation (in a female) unaccompanied by evident crossing over betweenforked and fused. The few exceptional cases may be accounted for in thisway; but, as pointed out when they were described, it seems at leastequally probable that all of them are due to experimental errors. We mustconclude that sister strands do not cross over with each other; or, if theydo, that the crossing over is rarely, if ever, unequal.

It is therefore unlikely that apparent non-crossover mutations in otherloci are to be referred to crossing over between sister strands.

"PRESENCE AND ABSENCE" AND QUANTITATIVE VIEW OF MUTATIONIt will be observed that the hypothesis advocated in this paper makes

bar, double-bar and round by reversion (or infrabar, double-infrabarand round by reversion) represent quantitative variations of the samesubstance. I n the case of bar and round, the hypothesis is the same asthe original and most special type of quantitative view, the "presence andabsence" hypothesis. But the present scheme differs from the earlier onesin that i t is based on definite evidence for the occurrence of unequalcrossing over. That is, the mechanism whereby the quantitative differ-ences are brought about is an essential part of the hypothesis. I n thepreceding section we have seen that there is definite evidence to show thatunequal crossing over is not usual in the production of new mutant types.It is especially noteworthy that this evidence was derived in part fromthe white locus of Drosophila and the variegated locus of maize,-twoof the best-known examples of loci that have produced large series ofmultiple allelomorphs. It is clear, therefore, that the bar case does notfurnish support to the idea that mutations in general are quantitativein nature. Even with respect to multiple allelomorphs, where the quanti-tative view has often been urged, i t is obvious that , a t least in the cases ofwhite and variegated, the bar evidence does not in any way support thatview.

ARE DEFICIENCIES DUE TO UNEQUAL CROSSING OVER ?The "section-deficiencies" described by BRIDGES 1917, 1919) and by

MOHR 1919, 1923 b) are probably to be interpreted as due to losses ofdefinite sections of chromosomes. It will be observed that bar reversionhas here been treated as due to the loss of a very short section; it mayaccordingly be described as a deficiency that is too short to show thelethal effect and other properties of the previously described deficiencies.GENETICS 0: Mr 1925

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144 A. H. TURTEVANT

When the case is stated in this way, the queston at once arises: is itprobable that notch and other deficiencies have also arisen throughunequal crossing over? If so, the contrary crossover should be a chromo-some that was double for a region corresponding to the deficient section.Such a chromosome has never been identified, bu t i t may be doubted if i twould be detected even if present. Furthermore, i t might well be lethaleven in heterozygous females, in which case it would not be capable ofdetection.

There is evidence that deficiencies may arise in other ways than byunequal crossing over. In a t least one case (BRIDGESnd MORGAN923)the section missing from a second chromosome was found to be present,bu t attached to a third chromosome. I n this case, then, the deficiencycan not have been due to unequal crossing over. The first deficiencydescribed, that for forked and bar (BRIDGES 917), occurred first as asingle female that had obtained the deficient X from her father. Herethe deficiency arose (either in a male or very early in the cleavage of afemale zygote) at a time when crossing over (and bar reversion) does notnormally occur. I n the case of notch, also, there is evidence that thedeficiency may originate a t stages other than maturation. LANCEFIELD(1922) records the occurrence of a notch (probably corresponding to thatof D . melanogaster) in Drosophila obscura; the mutation was first detectedas two females from a pair mating that gave numerous offspring. I n thiscase the deficiency must have originated in the gonial cells of one parent,unless the two notch females received their notch chromosomes from thefather, in which case it is just possible that they came from two spermsderived from a single spermatocyte. But in this case the hypothesis ofunequal crossing over remains as improbable as before. I have observedtwo cases in D. melanogaster that represent "somatic" (i.e., not occurringat the maturation divisions) occurrences of notch. I n one case three notchfemales were produced from a single mother. The X's of the mother wereattached, and the notch daughters, like all their sisters, did not carry apaternal X. These three females were all sterile, so here it was not possibleto demonstrate that the new type was actually notch; but the numerouscharacters of notch make the identification very probable. The othercase also occurred in a line in which the females all had attached X's. Afemale, from a line with no notch ancestry, was notch in the left wing b utnot in the right. The offspring showed tha t this female was, like hermother, heterozygous for several sex-linked genes. These included scute,3 units to the left of notch, and crossveinless, 10 units to the right of it .Some of the eggs of the mosaic carried notch, but many of them did not.

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 145Furthermore, tests showed that scute and crossveinless were in oppositechromosomes in both types d eggs; that is, the mutation to notchoccurred at a cleavage division, and was not accompanied by crossing overbetween s a t e and crossveinless. From these three instances we mayconclude that the notch deficiency may arise at stages in the life cycle atwhich crossing over and bar reversion do no,t normally occur, and, in thethird case, there is definite evidence that crossing over did not occur.While it may still be supposed that unequal crossing over will sometimesgive rise to section deficiencies, the evidence indicates that the threebest-known exampIes of section deficiencies in Drosophila have not arisenin that way.

UNEQUAL CROS S I NG OVER AND THE EXACT NATURE OF S YNAPS I SThe data on crossing over have all indicated consistently that when two

chromosomes cross over they do so at exactly corresponding levels. Thecase of bar is the first one in which any inequality of crossing-over levelshas been detected; and we have seen in the preceding sections that ananalysis of other possible instances of such an occurrence makes it probablethat they must be explained in some other way. The case of bar is clearlyquite exceptional. But it does serve to suggest that the exact correspon-dence of crossover levels, that is so constant, is not to be referred to aproperty common to all the genes. For unequal crossing over occurs infemales that are homozygous for bar or for infrabar, and in such femalesthese loci are alike in the two X chromosomes that cross over unequally.I t is difficult to imagine how the chromosomes can pair so extremelyexactly as they must do, unless in some way like genes come to lie sideby side. But the present case indicates that this interpretation will haveto be applied with some caution.

SUMMARY1. Sixteen different kinds of changes at the bar locus are shown to occur

exclusively, or nearly so, in eggs that undergo crossing over a t or near thebar locus.

2 . This result can be explained if it is supposed that such crossovers areunequal, so that one daughter chromosome gets two representatives of thebar locus while the other receives none.

3. Only one mutation in this locus has been shown to have occurredin the germ track of a male. This one gave rise (from bar) to a new andless extreme allelomorph called infrabar.

4. Infrabar does not appear to represent a quantitative change in thebar gene.GENETICS 0: M I 925

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146 A. H. S T U RT E V A N T5 . When, by unequal crossing over, bar and infrabar come to lie in the

same chromosome, they maintain their separate identities, and may berecovered again.

6. In such double forms the two elem,ents also maintain their sequencein the same linear series as the rest of the genes. I t is thus possible toobtain bar-infrabar and also infrabar-bar. These two types look alike, butcan be distinguished by their origin and by the usual tests for determiningthe sequence of genes.

7. Facet counts are given for all the possible combinations of thefollowing members of the bar series: round, infrabar, bar, double-infrabar,bar-infrabar, double-bar.

8. Analysis of these data shows that two genes lying in the same chro-mosome are more effective on development than are the same two geneswhen they lie in different chromosomes.

9. A general survey makes it seem improbable that many mutationsin other loci are to be explained as due to unequal crossing over.

LITERATURE C ITEDBRIDG ES, . B., 1917 Deficiency. G enetic s 2: 445-465.1919 Vermilion deficiency. J our. Gen. Physiol. 1: 645-656.

1921 Triploid intersexes in Drosophila melanogaster. Science N. S. 54: 252-254.BRIDGES,C. B., and MORGAN, . H., 1923 T he third chromosome group of m ut an t charactersof Drosophila melanogaster. Carnegie In st . Wa shington Publ. 327. 251 pp.EMERSON,R. A., 1917 Gen etical stu die s of variegate d pericarp in maize. Genetics 2: 1-35.HERSH,A. H., 1924 T he effect of te mp eratu re upon th e heterozygotes in th e bar series ofDrosophila. Jour. Exper. Zool. 39: 55-71.HERSH,R. K., 1924 T he effect of temp eratu re upon the full-eyed race of D rosophila. Jour.Exper. Zool. 39: 43-53.KRAFKA,., 1920 The effect of temperature upon facet number in the bar-eyed mutant ofDrosophila. Jour. Gen. Physiol. 2: 409-464.LANCEFIEW, . E ., 1922 Link age relatio ns of t he sex-linked char ac ters of Drosophila obscura.Genetics 4: 335-384.MAY,H. G., 1917 Selection for higher an d lower facet num bers i n th e bar-eyed race of Dro-sophila an d the appe aranc e of reverse m utatio ns. Biol. Bull. 33: 361-39.5.METZ,C. W., 1916 Chromosome studies in th e Diptera . 11. Th e paired a ssocia tion of chromo-somes in the Di pte ra and its significance. Jour. Ex per. 2001.21: 213-279.M O H R ,0 .L., 1919 Ch arac ter changes caused by m utatio n of a n entire region of a chromosomein Drosophila. Genetics 4: 275-282.1923 a A somatic m utatio n in the singed locus of t he X chromosome of Drosophila melano-gaster. Hereditas 4: 142-160.1923 b A gene tic and cytological an alysis of a sec tion deficiency involving four units of th eX chromosome in Drosophda melanogaster. Zeitschr. indukt. Abstamm. u. Vererb. 32:108-232.N O R G A N ,. V., 1922 Non-criss-cross inheritance in Drosophila melanogaster. Biol. Bull. 42:267-274.MORGAN, . H., and BRIDGES,C. B., 1916 Sex-linked inheritance in Drosophila. CarnegieIns t. Wa shington Publ. 237. 87 pp. 2 pls.

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UNEQUAL CROSSING OVER AT THE BAR LOCUS 147MULLER,H. J., 1920 Further changes in the white-eye series of Drosophila and their bearing

on the manner of occurrence of mutation. Jour. Exper. Zoo1.31: 443-473.SEYSTER, . W., 1919 Eye facet number as influenced by temperature in the bar-eyed mutant

of Drosophila melanogaster. Biol. Bull. 37: 168-182.STURTEVANT,. H., and MORGAN, . H., 1923 Reverse mutation of the bar gene correlatedwith crossing over. Science N. S. 57: 746-747.TICE, S. C., 1914 A new sex-linked character in Drosophila. Biol. Bull. 26: 221-230.WEINSTEIN,A., 1918 Coincidence of crossing over in Lkosophila melanogaster. Genetics 3:

135-173.ZELENY, ., 1919 A change in the bar gene of Drosophila involving further decrease in facet

number and increase in dominance. Jour. Gen. Physiol. 2: 69-71.1921 The direction and frequency of mutation in the bar-eye series of multiple allelomorphs

of Drosophila. Jour. Exper. 2001. 34: 203-233.1922 The effect of selection for eye facet number in the white bar-eye race of Drosophilamelamgaster. Genetics 7: 1-115.1923 The temperature coefficient of a heterozygote with an expression for the value of a

germinal difference in terms of an environmental one. Biol. Bull. 44: 105-112.ZELENY, ., and MATTOON,. W., 1915 The effect of selection upon the "bar-eye" mutant of

Drosophila. Jour. Exper. Zool. 19: 515-529.