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9.19
o
9B
Geneson the sarnechromosome
tendto be inheritedtogether
jn 1908,British biologistslVilliam
Batesonand Reeinald
Punnett (originator ofthe Punnett square)discoveiedan
inheritancepattern that seemedtotally inconsistentwith
Mendelian principles. Bateson and punnett were working
with two characteristicsin sweet peas,flower color and
pollen shape.They crosseddoubly heterozygousplants
(PpLl) that exhibited the dominant traits: purple flowers
( ex pr es s io no f th e P a l l e l e ) a n d l o n g p o l l en grai ns (expr es s ion of th e I a l l e l e ). T h e c o rre s p o ndi ng recessi ve
traits are red florvers(in pp plants) and round pollen (in
Purplelong
284
tta
/ / plant s ) .
a1
Purpleround
71
The top part of Figure9.18iilustratesBatesonand punBed long
1l
71
nett's experiment.When they looked at just one of the two
^'
Heo round
characteristics(that is, either crossPp X Pp or crossIi X
LI),they found that the dominant and recessiveallelessegEXPLANATION:
LINKEDG E N E S
regated,producing a phenotypic ratio of approximately 3i1
/ PL
\
Parental
for the offspring, in agreementwith lv{endel'ssegregation
/o)
diploidcell
principle. However,when the biologists combined their
cf1-3
\
/
PpLt
data for the two characteristics,
\p/
/
they did not seethe 9:3:3:I
ratio they predicted for a dihybrid cross.Instead,as shown
Meiosis
in the table, they found a disproportionately large number
of plants (339 of 381 observedoffspring) r,vitheither purple florversand long pollen (284 of 381, almost 75o/ooithe
t ot al) or r e d fl o w e rsa n d ro u n d p o l l e n (55 of 3gl , about
I4o/oof the total). Theseresults were not explained until
severalyears later, when other studies r.,r.il.d that the
Fertilization
genesfor flower color and polien shape are on the same
chromosome.
Qnorm
The number of genesin a cell is far greater than the
number of chromosomes;in fact, each chromosome has
pl
thousandsof genes.Genesthat are iocated ciosetogether
Most
on the samechromosome,calledlinked genes,tenJto be
offspring
inherited together.As a result, they generailydo not follow
Mendel'sprinciple of independent assortment.As shown
in the "Explanation"part of the figure,meiosisin the heterozygous (PpLl)sweet-pea plant yields mostly two geno3 purplelong':1 red round
types of gametes(PL and pl) rather than equal numbers of
Not accountedfor:purpleroundand red long
the four types of gametesthat would result if the flowercolor and pollen-shapegeneswere not linked. The large
Figure9.18 Experiment
involvinglinkedgenesin the sweetpea
numbers of plants with purple long and red round traits in
the Bateson-Punnettexperiment resulted from fertiiization among the PI and pl gametes.Bnt what about the
Whatarelinkedgenes?
a
smaller numbers of plants with purple round and red iong
traits?As we seein the next module, the phenom..ron oi
auosouotql sues
aq] uo:eqtaSot asoll ale rlol rlaqt esne:aqraqla8otpalr:aqurJq o] puat
crossingover accountsfor theseoffspring.h.u,
tEq] sauag
?
9;19
o
9B
Crossing
overproducesnew combinatlons
of alleles
jn jvlodule8.18,we saw
that during meiosis,crossingover
between homoiogous chromosomesproduces nelv combinations of alielesin gametes.Figr.rre9.19A reviervsthis pro_
cess,showing that two linked genescan give rise to iou,
different gametegenotypes.Gameteswith genotypesAB
174
UN ITII
CELLULR
AR
E PR o D U CTION
A N DGE N E TIC S
and ab carry parental-type chromosomes that have not
been altered by crossing over. In contrast, gameteswith
genotypesAb and aB are recombinant gamet;s, They carry
new combinations of alleiesthat result from the exchange
of chromosome segmentsin crossingover.Crossingovir
FFi:
.-
(##) f-+4)
-*ffi--x Y'
GG
crossinsover
\_-/
\_-/
Gametes
Figure9.19A Review:Productionof recombinantgametes
EXPERIMENT
Blackbody,
vesrgrarwrngs
ggtt
Maie
The discoveryof how crossingover createsgametediversity confirmed the relationship between chromosome
behavior and inheritance. Some of the first experimentsto
demonstratethe effectsof crossingover were performed in
the laboratory of American embryologist Thomas Hunt
Morgan in the early 1900s.Morgan and his colleaguesused
the fruit fly Drosophila melanogasterin many of their experiments. Often seen flying around overripe fruit,
Drosophila is a good researchanimal for studies of inheritance. It can be grown in small containers on a mlxture of
cornmeal and molassesand will produce hundreds of offspring in a few weeks.Using fruit flies,geneticistscan trace
the inheritanceof a trait through severalgenerationsin a
matter of months.
Figure9.198showsone of Morgan'sexperiments,a cross
between a wild-type fruit fly (gray body and long rvings)
and a fly with a black body and undeveloped,or vestigial,
wings. Morgan knew the genotypesof theseflies from previous studies.Here we use the follorving genesymbols:
G : gray body (dominant)
g : black body (recessive)
I : Iong i vi ngs(domi nant)
/ : vestigialwings (recessive)
Blackvestigial. Grayvestigial
ffi
Blacklong
h cGld
\)r&/
w'
,ffi$)
\V7
944
185
Parent4l
types
Recombinants
frequency= 3gl reiombinants = 0,17or 17%
,,
: 2300t ot alof f s pr ing. . :
EXPLANATION
gl
ffiffii€Isr4
gL
^l
'lnt !
/ f o mrl o \
GD
@GD
%
gt
.<\>__\
GL\/
wrywry
I
G/\/
st\/
gr
^t
r_CD
@ED
nl
.
@€ED
(ffiED
(:-:EE
I
sL\
@GD
/
I
/--"--\g
t\
lcere/
\_-/
Sperm
at
gl
gt
gr
I
Eggs
'
Sgil
(mate)
@tr
nl
vL
gl
@EB
u r r s pnng
Figure
9.19B Fruitflyexperiment
theroleof crossing
demonstrating
overin inheritance
In mating a gray fly with long r,vings(genotvpe Ggl/ )
with a black fly with vestigialwings (genotypeggl/), NIorgan performed a testcross(seeModul e 9.6). If the ge nes
had not been linked, then independentassortmentrvould
have produced offspri ng i n a phenotypi c rati o of 1:1 : 1: 1
(f gruy body,long wings; I blact body, vestigialwings;
{
gray body, vestigialwings; and j black body*,long wings).
But becausethesegeneslverelinked, Morgan obtainedthe
resuitsshor,vnin Figure 9.198: tr{ost of the offspring had
parental phenotvpes,but 17o/oof the oftipring flies rvere
recombi nants.The percentageof recombi nantsi s called
the recombination frequenry.
When Morgan first obtained these results,he did not
know about crossing over. To explain the ratio of offspri ng, he hypothesi zedthat the genesrverel i nked and
that some mechanismoccasionallybrokethe linkage.Tests
of the hypothesi sproved hi m correct, establ i shi ngthat
crossing over lvas the mechanism that "breaks linkages"
betweengenes.
The lower part of Figure 9.198 explainsN{organ'sresults
in terms of crossingover.A crossoverbetween chromatids
of homoiogous chromosomesin parent Ggll broke linkagesbetween the G and I alielesand betrveenthe g and I
alleles,forming the recombinant chromosomesGl and gl,
Later stepsin meiosis distributed the recombinant chromosomesto gametes,and random fertilization produced
the four kinds of offspring lv{organobserved.{-'q,
3
a
recombines
linked genes into assortmentsof aileles not
tound in parents.
Returnto the datafor sweet-peaplantsin Figure9.1B.
frequencyfor the flower-color
Whatisthe recombination
genes?
and pollen-length
C h a p t e r9
P a t t e r n so f I n h e r i t a n c e
L75
9.20
o
9B
Geneticists
usecrossoverdatato nrapgenes
'..1=:orking
mostly-with Drosophila,T.H. Morgan and
his
students produced a virtual eipiosion in
our understand_
ing of genetics.Inthe.photo in Figure 9.2)A,Morgan
(back
far right), severalstudents,and a skeleton
1ow,
are cerebrating the return of Alfr.ed H. Sturteyant (left
foreground)
from World lVar I military service.Or,.
of Sturtevant,s
major contributions to genetics.wasan approach
for using
crossoverdata to map geneloci. Sturtevant
startedby asl
suming that the cha"ce of crossingo,r.r1,
upproximateiy
e.qualat all points on a chromoro-!. H. then
hlpothesized
that the farther apart two genesare on a chromosome,
the
higher the probability that a crossoverwould
occur be_
trveen them. His reasoning ,,vaselegantly
simple: The
greaterthe distancebetween two genes,
the moie points
there are betlveenthem where c.issing
over can occur.
Urith this principle in mind, Sturteva.,i
began using re_
combination data from fruit_fly crossesto
as'signto g"enes
relativepositions on chromosomes_that
is,to map genes.
Figure 9.20Brepresentsa part of the chromosome
that
carries
genes.for-black body (g) and vestigial
.the-linked
rvings (l) that we described in lvloduie gli9.
This same
chromosomealso carriesa genethat has a
recessiveajlele
(we'll call it c) determining cinnabar
eye color, a brighter
red than the wild-type coloi. Figure g.ZdBshows
the actual
crossover(recombination) frequenciesbetween
these alle_
les, taken two at a time: l7o/obeiween the g and
I alleles,go/o
behveen g and c, and 9.5o/obetween I and."c.Sturtevant
rea_
soned that theseyalues representthe relative
distancesbe_
tween the genes.Becausethe crossoverfrequencies
betlveen
g and c and betrveen I and c are approximaiely
half that be_
tween_gand l, gene c must iie rorighly midway
between g
and/. Thus, the sequenceof theseg.rr., on one
of the fruit_
fly chromosomesmust be g-c-l (oithe equivalent
l_c_g).
Yearslater it was learned that Sturtevant'sassumption
that crossoversare equally likely at all points on
a chromo_
some was not exactlycorrect. Still, his method of
mapping
genesworked, and it proved extremely valuable
in esiabl
Ii3- , $
:\.
'.1
.aF
- 1=r's.iZL\'
'---i
Chromosome
<_ 1 7 %+_
176
u N trl t
c E L L U L ARREp R o D U cl oN
A N DGE N E TTcs
_>
Recombination
frequencies
Figure9.208 Mappinggenesfromcrossoverdata
MUTANT
PHENOTYPES
Short
anstae
Black
(s)
Cinnabar Vestigial
eyes
wings
(c)
( /)
.\_\
.@t
)1i
.X.€:,6
"eJ
r.a
\
Brown
eyes
J'ry"
Fre ^JruD
'l \ / ) **r
\4
N
Longaristae Gray
(appendages body
on head)
(G)
Red
(c)
@
Normal
wings
(r)
\a
ru
Red
eyes
WILD-ryPEPHENOTYPES
Figure9.20C A partialgeneticmap of a f ruit_fly
chromosome
lishing th.erelativepositions of many other fruit_fly
gene
Eventually,enough data were accumulatedto reveal
tha
Drosophilahas four groups of genes,corresponding
to it
four pairs of chromosomes.Figure 9.20Cis a genetic
mal
showingjust five of the geneloci on part of one chromo
some:the loci we'vecalledg, c, and /, and two others.
No
tice that eyecolor is a characteristicaffectedby more
thar
one genelocus.Here we seethe cinnabar_eye
and brown.
eyegenes;still other eye-colorgenesare found elsewher
(seeModule 9.22).For all thesegenes,ho.rvever,
the wildtype allelespecifiesred eyes.
Todai',with DNA technology,geneticistscan determine
the actual distancesin nucleotidesbetweenlinked genes
Thesenewergeneticmaps generallyconfirm the relatiie
po_
sitions establishedby Sturtevant'smapping method.c\
6e
N
Figure9.20A A partyin Morgan,s
flyroom
9% -*1;9.5%
+
YoudesignDrosophila
crosses
to providerecombination
datafor a genenot includedin Figure9.20C.The
gene
hasrecombination
frequencies
of 5% with the veitiqial_
wing (/,)
locusand 5oowith the cinnabar-eye
(cllocui.
Whereis it locatedon the chromosome?
rlol J?qeuurtpuE
aq1uaanlaqden;leq lnoqy
IvrSrlsa,r
\t
22,
v:.--,
o
9C
genesexhibita uniquepatternof inheritance
Sex-linked
*es ides bea ri n g g e n e sth a t d e te rm i n e s e x,the so-cai l ed
sex chromosomesof many speciesalso contain genesfor
characteristicsunrelated to femalenessor maleness.Any
genelocated on a sex chrornosomeis called a sex-linked
gene. Sex-linked genesunrelated to sex determination are
most often found on X chromosomes.However, in some
animals, such as fruit flies and certain fishes,the Ychromosome does carry some genesunrelatedto sex determination. Such genesgive rise to traits appearing only in
niales and passedonly from father to son. In humans,
there is as yet no
conclusive evidence that the Y
c h r omosome carripc
Figure9.22A Fruit{lyeye color,a sex
linkedcharacteristic
P
-
r ar l- av a
qPncq
rrnrc-
l a ted to mal e sex
determination.
The figures here
illustrate inheritance patterns for
white eye color in
the fruit fly, an Xlinked recessive
trait. Wild-type
fruit flies have red
eyes; white eyes
are very rare (Figure 9.22A).We use
uppercaseietter R
for the dominant,
wild-type, red-eye
alleleand r for the
recessive, lvhiteeye allele.Because
these alleles are
carried on the X
chromosome,
we showthem assuperscripts
to the letter{.
Thus, red-eyedmale fruit flieshavethe genotypeXRy:
white-eyedmalesareX'I The Ychromosomedoesnot
havea genelocusfor eyecoior;therefore,
the maie'sphs_
notyperesultsentirelyfrom his singleX-linkedgene.In the
female,XRXRand XRX' flieshavered eyes,and X'X'flies
havervhiteeyes.
A white-e1'edmale (X'Y)wtlI transmit his X, to all of
his femaleoffspring, but to none of his male offspring.This
is because,to be female,his daughtersmust inherit his X
chromosome,but his sonsmust inherit his l'chromosome.
A s show n i n Fi gure 9.228, rvhen the fem ale par ent is a
dominant homozygote (XRXR) and the mrle parent is Xrf;
all the offspring have red eyes,but the t'emaleoffspring are
ali carriers of the allele for rvhite eyes.
In Figure 9.22C, we seethat when a heterozygousfemale (XRX') mates with a red-evedmale lXRY), half the
male offspring are white-e,vedand half are red-eyed.All the
female offspring of this crosshar,ered evesbecausethey
inherit at leastone dominant allele(from their father).Half
of the female offspring are homozvgous dominant because
they inherit their mother's R a1lele.The other half of the
femalesare heterozvgotes(X'XR; like their mother.
As Figure 9.22D indicates, if a heterozygousfemale
mateswith a rvhite-eyedmale, there is a 50% chancethat
each offspring will have r.r'hiteeyes(resulting from genotype X'X' or X'I), regardlessof sex.Daughterswith red
eyesare heterozygotes,whereasred-eyedmale offspring
completely lack the recessive3|lgls.au
Q
3
A white-eyedfemaleDrosophila
is matedwith a redeyed(wild-type)male.Whatresultdo you predictfor the
numerousoffsorino?
'l,irY-) pr.ir-atrqa 3q IIra
Suirdsgo aFu IIe.'(rxyyl sno8izo:ataqlnq paia-pa.rac 11u 8ur:dryo a1eual1ry
"lW."W
allala
r = white-eyeallele
Figure 9.22B Homozygous,
red-eyed
femaler white-eyedmale
178
uN trl t
Figure 9.22C Heterozygous
female;<
red-evedmale
CELLULR
AR
E p R o D U c loN
A N DGE N E Ttcs
Figure9.22D Heterozygous
femfe x
white-eved
male
,
..
l .'
, ,, ,,,, 1.
..=
r-.
Sex-linkeddisordersaffectmostlymales . '9i23
5
hastaughtusmuchabouthumaninheriFruit-flygenetics
includingred-green
humanconditions,
of
number
A
tance.
dystro- Victoria
type
of muscular
and
a
hemophilia,
blindness,
color
(X-linked)
that
alleles
recessive
sex-linked
from
phy,result
fruit
in
trait
white-eye
way
as
the
in
the
same
areinherited
sexwhy
recessive
us
shows
model
also
fruit-fly
flies.The
men
in
frequently
more
much
Iinkedtraitsareexpressed
thanin women.Likea malefruitfly,if a maninheritsonlyone
Alexandra
allele-fromhismother-theallelewill
recessive
sex-linked
N i c h o l a sI
a womanhasto inherittwo such
of Russia
In contrast,
beexpressed.
alleles-onefromeachparent-to exhibitthe trait.
discolorblindnessisa commonsex-linked
Red-green
cells
of
light-sensitive
by a malfunction
ordercharacterized
involving
in the eyes.lt is actuallya complexof disorders,
vision Figure9.238 Hemophiliain
color
A personwith normal
X-linkedgenes.
several
the royalfamilyol Russia
someonewith
canseemorethan I50 colors.ln contrast,
For
some
canseefewerthan25.
colorblindness
red-green
and the firstsymptomsappearin earlychildare males,
people,redhuesappeargray;othersseegrayinaffected
standing
up.
when
the childbeginsto havedifficulty
hood,
or red-weak,
steadof green;still othersaregreen-weak
he
12.
Eventually,
by
age
wheelchair-bound
inevitably
He
is
are
Mostlymales
of thesecolors.
shades
to confuse
tending
becomes
breathing
normal
and
(lf
wasted,
severely
becomes
femaleshavesomedefects'
but heterozygous
affected,
Deathusuallyoccursby age20'
you probablycannot difficult.
colorblindness,
youhavered-green
dystromuscular
Duchenne
a severedisease,
For
such
9.23A.)
7 in Figure
seethe numeral
population,
general
U.S.
In
the
phy
common.
is
relatively
traitwith a long,
recessive
Hemophiliais a sex-linked
andthe disease
bleedexcessively aboutonein 3500malebabiesis affected,
Hemophiliacs
history.
well-documented
populations.
In one
inbred
in
some
common
more
is
even
alan abnormal
theyhaveinherited
wheninjuredbecause
out
of
every
one
instance,
for
in
Indiana,
community
Amish
mostserilelefor a factorinvolvedin bloodclotting.The
disease.
the
with
is
born
100
males
maybleedto deathafterrelaouslyaffectedindividuals
(discussed
in Chapter
Withthe helpof DNAtechnology
or cuts.
tivelyminorbruises
muscauses
Duchenne
gene
defectiveness
whose
12),the
A h i g h i n c i d e n c eo f h e mo P h i l i ahas
point
particular
on
at
a
mapped
been
has
culardystrophy
pla g u e d th e ro y a l fa mi l i e so f Europe.
for
a
codes
allele
gene's
wild-type
the X chromosome.The
T h e fi rs t ro y a l h e mo p h i l i a c s e e m sto
present
musin
normal
is
protein
calleddystrophin,which
ha v e b e e n a s o n o f Qu e e n Vi c tori a
patients.r"a
in Duchenne
clebut missing
( 18 i 9 - 1 9 0 1 )o f En g l a n dl.t i s l i k e l ythat
I
u u EEl
t he h e m o p h i l i aa l l e l ea ro s eth ro ugh a
m u ta ti o ni n o n e o f th e g a m e te so f V i ct ori a ' smo th e r o r fa th e r,m a k i n gV i cto. emor ia a c a rri e ro f th e d e a d l ya l l e l e H
ph i l i a w a s e v e n tu a l l yi n tro d u c e d i nto
and
t he ro y a lfa m i l i e so f Pru s s i aR, u s si a,
S p a i nth ro u g h th e m a rri a g e so f tw o of
V i c to ri a ' d
s a u g h te rsw h o w e re c arri ers.
T h u s ,th e a g e -o l dp ra c ti c eo f s tre ngth-
i
i
i
I
i
i
I
I
I
i'
5
p
F
H
E.
eninginternational
spread
effectively
by marriage
alliances
hemophilia
nations.
throughthe royalfamiliesof several
Thephotographin Figure9.238showsQueenVictoria's
who was
herhusbandNicholas,
Alexandra,
Sranddaughter
the lastczarof Russ ia,
pedigree
andtheirsonAlexis.The
useshalf-colored
carriheterozygous
symbolsto represent
ersof the hemophilia
Asyoucanseein the pedigree,
allele.
Alexandra,
wasa carrier,
likehermotherandgrandmother,
andAlexis
hadthe disease.
musAnother
isDuchenne
disorder
recessive
sex-linked
culardystrophy,a conditioncharacterized
by a progressiveweakenino
Almostall cases
and lossof muscletissue.
fu**,
,
a
NeitherRudynor CarlahasDuchennemuscular
but theirfirstson doeshaveit. lf the couple
dystrophy,
hasa secondchild,what is the probabilitythat he or she
will alsohavethe disease?
P atruPqrC/I ) t/l
Ly lu?tnu aql llrequl I[s 3l?u e ]xql atuPqr Z/I x pJlqr alEu Jo
x
The discoveryof sex-linked genesand their pattern of
inheritance in fruit flies and humans was one of many
breakthroughs in understanding how genes are passed
fron one generation to the next. During the first half of
the twentieth century, Mendei's work rvasrediscovered,his
principleswere reinterpretedin light of chromosomalbehavioi during meiosis,and the chromosometheory of inheritance wai firmly established.The chromosome theory
set the stagefor another explosion of experimentalwork in
the secondhalf of the twentieth century. This work was
mostly in molecular genetics'an arearve explorein the next
three chapters.
C h a p t e r9
P a t t e r n so f l n h e r i t a n c e
179