!
-56FALCONER: Yes, I think if I understood you right, that is a good
point.
The graph that you saw for litter size of the growth rate selected
mice were the litter sizes of those animals actually selected, of the parent
animals that were selected for their high growth rate, and I do not want
you to take that experiment too seriously for that reason, because the basis
of that c_mparison between the lines selected for litter size itself and
the lines selected for growth rate is a litte_ different, because in the one
case you havethe
progeny of the selected individuals and in the other case
you have the selected individuals themselves, and I think that is one of the
reasons why the gene l_vel is different.
:
You see, the level was higher all through for the correlated responses
than for the direct responses.
I think that is the main reason for it.
I
think one can only look at the general slope of these lines.
YO_:
Thank you, Dr. Falconer.
I think we will take a short recess now.
(Recess)
PART II
YOHE:
SECTION 2
Our next speaker is also from Edinburgh, Dr. Alan Robertson.
Dr. Robertson did work at Cambridge, he is now with the Institute of Animal
Genetics in Edinburgh.
He tells me that hehad
considerable training in
chemistry, but thathls major field at present is population genetics, and
its application to livestock breeding, particularly dairy catt la.
He has
also done work with Drosophila.
Like Dr. Falconer, he is in this country to appear at the Symposlam
to be held shortly on quantitative genetics.
I think it is very interesting that Dr. Robertson serves very much
in the same capacity as Dr. Lush does to this organization, except
Dr. Robertson serves for a group of cattle breeders, the Dairy Cattle Club
in Cambridge.
I think it is also interesting that when Dr. Lush visited
-57Britain, that he appeared before that group and today we are very happy that
Dr. Robertson returned and can appear before th2s group.
Dr. Alan Robertson.
_
ROBERTSON:
Mr. Chairman, it is indeed a great honor and a pleasure
to be able to talk to such an influential group.
I am rather afraid though
that from your point of view I shall get more out of you than you will get
out of me, but after all, that is what I came for, so why should I worry.
Now, first of all, I am not responsible for my title.
I think the
man who wrote my title must have thought I was running for office.
He says,
"A theoretical and practical consideration of ceilings and plateaus."
Well,
it is very much a.point of view whether it is a ceiling or whether it is a
plateau.
However, I suppose it is Mike Lerner who brought this word plat_e_u
into the subject when people were talking about cei_lings.
_at
I am going to talk about or use as sort oftext
is a selection
program with Drosophila and tie things up with that selection _rogram.
is described on this sheet which is being handed out.
It
The actual wrlte-up
was wrlt_en while I was listening to the election results last Thursday
night, so it is not perhaps as coherent as it might have been.
We took a large population of Drosophila which we had had in the lab
for a while, a large random breeding population of about five thousand
flies and selected for a character which is of very little intrinsic importance to the animal.
abdomen.
It is the number of bristles on particular parts of the
A fly cares very little whether it has the bristles or whether it
has not, at least that is my guess, the fly may think differently.
little relation to reproductive fitness.
It has
We then took this basic population
to pieces genetically.
We got herltability estimates by all the means we could and then we
settled down and selected, different sorts of selection, mass selection
and family selections just to see whether the basic ideas worked.
-58-
(The following are mimeographed sheets handed out by Dr. Alan Robertson.)
The discussion of selection limits will be centered on a selection
experiment using Drosphila.
The character s_lected was a count of abdominal
bristles which is probably of little importance to the animal and not affected
by natural selection.
Different methods of measuring heritability agreed that
it was in the neighborhood of 50%. Different programs of selection were used
for up to seven generations.
These included three different intensities of
mass selection and also half-sib and full-sib family selection.
are given over leaf.
The results
The agreement with prediction is reasonably good except
that the response to full-sib family selection is less than expected.
However,
within each experiment there was definite divergences between replicates.
The iO lines at thehighest intensity of mass selection were carried on for
30 generations.
variation.
Each line developed its own behavior, both as to mean and
Some lines continued to respond to selection throughout while some
responded very little in the later generations.
A notable feature of these
latter lines was that in many of them, a great deal of genetic variation re_
mained.
Detailed analysis of lethal genes was possible and many of the lines
proved to be carrying lethals at high frequencies.
This suggests that the
heterozygotes were being selected.
Four cases were dealt with in more detail
and this proved to be true in all.
However, these were by no means all the
story.
Heritability analyses proved _ow to be valueless in predicting gain
due to selection. _ Two lines are presented on the sheet.
The character has altered from one of no importance to the animal to an
important part of fitness.
pondingly.
The genetic situation has also been altered corres-
The relevance of these results to the problem of selection limits
will be discussed.
-59Initial Population.
standard deviation 3.4
Mean 35.4
Heritability estimates.
Offspring -dam regression
Half-sib correlation
Full-sib correlation
0.51_0.07
0.46_0.11
0.52_0.07
Response to selection.
Heritability of 0.50 assumed.
Individual,
Upwards
After _ _eneratlons.
20/100
20/75
49.9
45.2
46.3
46.4
47.0
44.0
20/50
41.9
40.5
41.7
Downwards 20"100
44.0
Av___t Pred.
48.6
47?2
45.2
41.4
26.4
26.9
47.3
45.6
43.5
27.3
25.1
27.6
26.7
25.5
20/75
28.1
27.2
28.6
28.o
2502
20/50
29.2
30.3
30.4
50.0
27.5
40.4
30.5
43.0
31.0
43.8
30.0
42.4
30.5
41,7
29,1
42.8
29.1
44.2
29.7
43.5
28.5
43.5
29.1
46.5
24.5
Half-sib
20/family
2/10
Upwards
Downwards
Full-sib
6/family
4/20
Upwards
Downwards
Lines after many generations of selection
_
70.7
S.D.
_
9.8
84.6
Av.
77-7
i1.9
Heritability.
Half-sib correlation
Full-sib correlation
0.23
0.22
Two-way selection.
Upwards
Downwards
Parents
0ffsoring
S.D.
89.2
64.2
78.5
65.0
lO.1
4,9
The upward response had been 5 in the last 12 generations.
L/5/30
_
S.D.
17.1
2.5
_,
3.7
5.1
Heritability
Half-sib correlation
0.80 in _
Full-sib correlation
0'.71in _
Daughter-dam regression
0.90 in (_
0.63 in
0.ii
The downward response had been i.O in (#and 2.5 in T in the last 12 generations
-60-
On the whole, on this population which had not been previously selected,
I
they did work.
You will see the basic results on:the reverse side Of this
sheet, which first of all Just describeathe
Standard Deviation of 3.4 and a Mean of 35.4.
original population with a
Theusual
ways of measuring
heritability are to look at the correlation between daughter and dam, to
look at the similarity between offspring from the same father and also to
look atthe
and father.
agreement.
similarity between full sibs which have both the same mother
These three heritability estimates were all almost too much in
Daughter-dam was .51.
The half-sibcorrelation
of 0_46 and
the full-sib correlation gave us an answer of 0.52, so everything was fine.
Then, we selected; first, mass selection or individual selection with
three different intensities of selection, both upwards and downwards.
To take that first line on the sheet,,individual selection upwards,
_20 out of i00 means that the extreme 20 flies out of i00 were chosen as
parents ofjthe next generation and there were five lines.
the score after five generations, 49.9, 46.3 and so on.
this in detail at the moment.
I have given
I am going into
I will not bother with the others.
age over the five lines was 47.2 and downwardswe
The aver_
got a considerab_l_
response with an average of 26.7.
Now, it was noticeable in that early experiment that all the lines
did not do the same thing.
Very soon they established for themselves a
definite position among the group of lines.
There was one llne which was the best high llne, another line which
was the worst high line, and the final differences after the five gener__
ations you will see;
there was one line which got to 49.9,_which is &n
improvement of 14, and there was another line Which only got to 4_, which
is an improvement of 9.
So, the different lines did_not all do the same thing, but on the
average they did more or less the right.thing.
The last two columns show
-61-
the average of all the lines and the predictedresponse
calculated from
the proportion selected, the amount of variation wehad
present and the
heritability, so the five up lines, 20 out of lO0, averaged47.2,
dicted, 47.3.
Not too bad. Well,
that is somewhatof
pre-
an understatement
shall we say.
It shows how useful it is to be able to average five results when
they deviate from 50 to 44 and then get Just the right average.
The down lines went down to 26.7 and We predicted they would go down
to 23.5, so they did not go down as far as we predicted.
Now, again, we did individual selection with two other intensities,
20 out of 75 and 20 out of 50.
tween
You will see there again a difference be-
the individual lines, but reasonably good agreement betweenthe
average of all the lines and prediction in the upward direction.
the downward direction
we did not get as far as we expected.
20 out of 75 instead of 25.2 expected.
Again in
28.0 in the
30.0 in the less intense against
27.3 expected, so it looked as though the herltability fell off in the
downward direction pretty rapidly within five generations.
We got some corroborative evidence as to that from the other means
of s_lection.
Let us look at those.
The half-sib selection, we have ten families of twenty individuals.
We count the twenty individuals and we pick out the best two families out
of the ten or the worse two families out of the ten and from those we
choose males and females which had not themselves been scored for the next
generation and so on.
We went upwards and downwards again, and you see
that with half-sib selection we got reasonably good agreement between prediction and expectation.
It did not go as fast as the individual selec-
tion, but with a character of such high heritability in which the performance tells you so much about breeding value, you would expect individual
selection to be faster than family selection, eapecially as in this
-62-
character, you can look at both sexes, which makes a lot of dl_ference.
Nowever, again we dld not go down as quickly as we thought we should.
In this experiment we can _ollow in detail what is going on as we go
down, because within each generation we have a structure, we have ten families in each of thethree
lines _nd from the variation between families
we can see what is happening to the genetic variation.
We did find that
genetic variation fell off very rapidly in the low lines.
The difference
between the families over the same slre was definitely less in three generations than it had been at the start.
The full-sib selection, four out of twenty, that is to say twenty
familie% with the same sire and dam, six animals measured in each family
and the best four families out of the twenty chosen to breed the next
generation.
This was deliberately chosen to keep the in-breeding the same as in
the half-sib selection.
Again reasonably good agreement between what we got and what we predicted, but in both cases at this tlme we did not get as far as we expected.
Going upwards, we expected to go up to 46.3, we got up to 43.5.
Going
downwards we expected to get to 24.5, and we got to 29.1.
So, for some reason the full-sib family selection did not give us
quite the response that we expected, but from a practical point of view, I
think if one had been trying to increase the milkyield of cows or increasing the egg production of hens, one would not have been disappointed, from
a practical point of view I think one is highly delighted to get even half
of what one expects.
think in all cases we got at least three quarters of what we expected.
So, the taking to piece_ of the initial population gave us results reasonably in expectation with theory.
We got our estimates of heritability, we used them to predict what
-63shouldhappen and it did happen close to what we predicted, so that was
reasonably satisfactory.
The complications were that the different lines did not all do the
same thing.
This may be due to the fact that we are dealing with Dros-
ophila, which only has effectively three chromosomes and has no crossing
over in one sex, so that the genetic material cannot get disentangled quite
as well as it can in an animal with a larger number of chromosomes.
Your
trouble may be that you are dealing with perhaps a smaller number of units. •
I might Just put in here that in many of these lines we relaxed selectionafter
the five generations, Just to see what would happen, and we
Just let them go for another five generations without doing anything to
them at all.
This bears on the problem o_ homeostasis, which I think will
be discussed later in the meeting.
It was rather surprising to find that very little happened.
We had
selected them pretty hard and pulled the mean quite a long wa_ from that
of the original population and it Just sat there and did not return to any
extent back to the original mean.
The population apparently did not mind
very much having its bristles changed.
Well, perhaps that is all right, at
least there wasn't this rapid return one might expect if the situation
was to any extent homeostatic.
However, we can discuss that more later
perhaps.
Then we stopped most of these populations, we stopped all the family
selections and we stopped all the intensities of individual selection,_
except the more intense, and we went on with the 20 out of i00 for thirty
generations and then interesting things began to happen.
Each llne rapidly
got its own individual characteristics, in such Characteristics as the
mean as I mentioned beforehand, definite omder became
established between the different lines selected in one direction.
particular line would also be rather more variable than others.
One
In some
-6_•
lines
....
on
the ratio of coun_males
got its own
individual
or so generations
selection.
to females
characteristics
most
was ratherpeculiar.
and eventualiy
of the lines had more
Some had not,
Each
after
about
or less ceased
some even at thlrty-five
line
thirty
to resp6nd
generations
to
were still
going on quite happily.
From
general
the later responses
predict
reason
is going to happen
at a high
speed
time
that I wouid bring
and then suddenly
in a bottle
H-1 got there,
whether
difficult
what
we expected
to count
was striking
it, then
There was another
Just keeping
when we measured
would
no
a fly which
which
stopped
had
generation
lines,
almost
the second
deal
and refused
depended
to respond
the response
lines
shall we keep,
which
stopped
0fthe
lines
it was not going
it was Still
going
generalization,
to decide
on it.
gotten
there
much
further.
and it tapered
off.
high lines,
it was
after
twenty-
about
shall we throw
very
fast,
but at the
on and it had beatenanyof
as to what was going
gave you the wrong
and a hundred
operation
and we had to make a decision
so any prediction
invariably
a great
it, this line
bristles
and it was a major
was the lowest
so we kept this line because
thlrty'fifth
I_expected
was that this llne having
line which
on gradually
generations
Now,
to
not a bet, at least a promise,
the fly had a hundred
It was going fast and then suddenly
race
groupj
of whiskey
it had or it had not, because
previous
some iines
stop for apparently
about _two months before
I must admit
are very
However,
away,
future,
difficult
bristles.
Now, this happene4
bristles
.........
_
Whatsoever.
a hundred
it is exceedingly
in the immediate
There was a bet in my particular
five
I think, _everal
"
that at any particular
What
on merely
before
one can make,
points.
Firstly,
go
to selection
to happen
the
in this
answer.
that almost
without
exception
in these
"65ten lines, five up and five down, when we did reach some sort of a plateau
or ceiling there was a considerable amount of genetic variation, a very
considerable amount, so that the population in some cases was a good deal
more variable than it had been when we started ....
""
We had started at about _0, we had gotten up to a level of 60 to 70,
in fact in some cases over 80.
The lines had stopped responding, but they
\
were fantastically variable.
produce uniformity.
There was no doubt that selection did not
We got our high lines, but lines in which some indi-
viduals are high and some are only mediocre.
In some cases we could take this situation to pieces in rather more
detail.
That is the advantage of'workingwith
Drosophila, if something
peculiar happens, you can utilize all the trick stocks and take out
chromosomes•and make them homozygous and see if they carry lethals and
so on.
You can take it to Pieces and see what is going wrong.
Now, out
of these ten.lines about eight of them turned eut to be carrying lethal
genes at high Trequencies.
When I say high frequencies, I mean that per-
haps thirty per cent of the chromosomes we took out would contain•a lethal
and
when we went Into it into more detail we would find that all these
would be carrying,the same lethal .
•
"
.C_.
_
0
/
• That would suggest that we were picking out the heterozygotes the
_ _'IV
_
.12!
whole
time
together.were
and mating
them
Of c°urse'
the
lethals
were dying_!_
and then
w_picking
out
the heterozygotes
again in
the
next generation.
,'_ !i
Ii_
5
In four of the lines we actually put our fingers on the individual genes,
produced heterozygous flies and saw how much they exceeded or were less
than flies without this lethal gene and our expectations were justified.
We found that the heterozygote was very definitely superior in high lines
or inferior in the low l_hes to animals which did not have the lethal gene.
It was really rather surprising that in so many of the lines we finished
up with genetic variation.
-66To digress a bit and discuss the extent to which this might happen
in a livestock population, this was a surprise to us, .there was nothing
obviously wrong with the lines and if you lo_ked at it fromthe
point of
view say of a population of cattle and wtnt into it in detail, it might
be very difficult to realize that you had such a situation.
You would find possibly that some of the bulls would have rather a
lower conception rate than others, they might have a conception rate perhaps
of 55 instead of 70, but some bulls do have a conception rate of 55% anyway.
It was a situation where it was possible to take it to pieces with the trick
stocks in the Drosophila, but if one did not realize it was there it might
be very difficult to put one's finger on it if one was dealing with cattle
or poultry, though one might see a decline in hatchability in the latter.
Before I go on to those I will take the slides, if I may, Just to indicate
the later behavior.
You can see the lines in the early generations.
the early generations _hey establish a definite order.
In
There is the best
high line and there is the lowest high line and here again there is the
lowest low line and the highest,high line.
The lines established definite
order very quickly, even though the amount of inbreeding we are doing is
comparatively slight.
We are p_cking out forty parents In each generation.
These were a few inbreds to find out what would happen on inbreeding.
This was the line which was concerned with the bottle of whiskey and you
see what happened, the whiskey was drunk at about there.
Well, that was certainly a little surprising, but there it is going
on and then suddenly it stops and refuses to go on any further.
This line, the low line, H-4, you can see it beginning to creep up,
in fact it kept on going and finished up somewhere there and we gave up in
disgust then, because to count ninety bristles on an individual is rather
hard work.
It is much nicer when you are dealing with lines like this in
which you find yourself counting eight.
- 67A-
Fig. 1 The result of continued selection.
- - - relaxed lines. K - inbred lines.
-67B-
14
;
=a
,_
HIGH
,_
i'o
LINES
•
•
•
/ .............i"
_?
.
•
_
4 ..... .-,_e._ ""_-- /
-"
\
2r.<_
3'o
3;
.....'_\
."
I0.
ds
"_"_
/
',
:
."........................
.__....
i.,o
_ /
-,.'
-
"...
"v
....._..;
_
-I ....
..,'_._.,..
H.I
...--H. 4
H 5
,/
2,
O.
•
"_-'-
2 F "-'_0
t
_P
V
14
/'.
I1
'
/H.
•
/."
i."-....._,_._..,
i/'x,,
d
H. 4
I_
V
v
",, ""'" i'X._
;
._.
/
_.
\\
•
#/
"_
O'
GENERATIONS
2
..,"
Voriability
in the
high
"... /
"--.-
! ,._-_
.".--." .t"
2"
Fig.
"%..""
-,.,, .. i/N
4
"
/
_P
lines.
I_
.-H o"e
-'"
"
"-H. 40"d'
-68-
Here
variable
This
again
peculiar
in some of the
line
L-5,
for
things
lines
happened.
and the
Instance,
The females
became
mean performance
I shall
exceedingly
go on into
dropped
more detail;
very
rapidly.
here
predictions as to what the lines were going to do did not come off.
again
This
line L-2 was kept on, because it had responded very little in the past few
generations.
Then suddenly three generations after this, down it shot.
There is some physiological peculiarity I think here.
In all the lines, one
after another, the female _uddenly went down very rapidly and became very
variable.
This is actual variability expressed as the coeff_clent of variation.
That is the standard deviation divided by the mean.
In the early genera-
tions very little happens and there is this lowjline, I think it is actually L-5 females, suddenly becoming very variable, the variation going up
fantastically, about six times as much as it was earlier.
There is another low llne female becoming variable.
some high lines.
Here wehave
This H-1 llne, finishing up more variable, even when we
take out the mean.
the base population.
In absolute terms it was very much more variable than
There was actually a llne which did finish up with
less variability than the basepopulation
Now, this is Just a slide to illustrate the peculiar behavior of females.
This is the ratio of counts in male to that in females.
You see again in
this line more or less when it began to become more variable, up shot the
ratio of males to females.
other lines.
There again are distinctive behaviors of some
Line H-1 has a definitely different ratio of male to female
count than llne L-5.
Now, of these lines we took two to pieces in even more detail and
those are given in the bottom half of the sheet.
To discuss these two lines, H-1 in rather more detail, we have selected
thls character for so long that it has become of great intrinsic importance
- 69-
o
s
to
f_
2o
GENERATIONS
Fig. 3 Variability in the low lines.
a_
s_)
.
- 70-
01
..IT
MEANS
l
l
iF\
i,/
/.\._
•
..........
O
!
/ w it
L.2
//
\,II.......
"
_.-"'-.-b;=.-.-;"--..-_:./
........
_/",,...-_..J_
..............
_,,.,
Z..... "_'-=..............
..,r....... _
. "-"
_...... _.s
""_"-:--"-:---_ .......
I0
IS
liO
iS
GENERATIONS
Fig. 4 Ratio of d I counts to _
counts.
""
IO
i_
-71-
i
,
to the animal.
.
f
The animal previously did not mind whether it had _orty
bristles or thirty'five.
Now, it is of greatest importance to _!ttwhether
it has forty or thlrty-flve, because we are going to:let itproduce
off-
spring in one case and not in the other.
We have made this character, previously unimportant to it, of the
highest importance.
We have almost made,it a part of reproductive fitness,
and we will now expect it to behave•in the genetically complicated manner
that we would expect components of fitness to behave, and this I suppose is
an•explanation of why we get peculiarities.
I think I myself would expect characters which are not of importance
to the animal to be pretty simply lnherited or thevariation
to be simply
additive, the heterozygote intermediate between the two hom0zygotes and
that is what seems to happen in the base population.
_,
I would expect characters closely connected with reproductive_fi_en_2
_
. .pm the whole to be inherited in a fairly complicated way.
_
If they were
inherited simply, naturally selection would have picked out those genes
and fixed them.
You expect, to my mind, characters llke shall we say
butter•fat content in cattle to have a high heritability and to respond to
selection, because there has been no natural selection for them previously.
I would expect characters like egg laying in poultry to havea
lowerS"\
heritability, because a hen which lays more eggs has always been liable tol
/
produce more offspring than a hen which laid less.
Now, we have made this bristle characteristic into something like the
number of eggs and we get a more complicated situation.
H-l-30, that is
the first high line at the thirtieth generation, with a male average of 71
and a female average of 85, an average of both sexes of 78, and there you
'
have the standard deviation.
Now, this line had responded very little in
the last twelve generations.
It responded flve bristles in twelve genera-
tions, in spite of the fact its previous level of response had been in the
-72"
order of four a generation.
That is to say, it had effectively s_opped,
it behaved as though there was no genetic variation left, but on analysis
there turned out to be a lethal gene present which in the heterozygote
increased the number of bristles by about fourteen.
You may then ask where
does this come from if in the initial population your variation was in the
order of threep but that is a matter for discussion.
We could not get any further, so we measured our heritability by halfsib correlation_and by full-sib correlation.
We got a heritability of
Well, now, that is a reasonable sort of heritability.
'
It is the
he_ftability of milk production in cattle and one hopes that one can
improve milk production in cattle by selection.
Now, we take the population and we take the top 20% of animals and we
mate them together, which we do normally under selection, that is the usual
selection procedure in this experiment, and we take the bottom 20% and we
mate them together.
The results of that are given half way down.
The top 20_, the parents average 89.2, and the offspring went down
to 78.5, which is very little difference from the generation in which
they started, which was half a bristle lower, so we tried to go upwards,
we did not get anywhere.
We tried to go downwards, the parents were 695.2,
and the offspring were 65.0.
So in a delightful situation in which you try
to go upwards you pick out your high parents and you go back to where you
started.
You try to go downwards, you pick out your low parents and you
go down to where they ar_ a heritability of 100% going downwards and a
heritability of nought going u_wards.
_:
Actually the explanations are quite simple.
Just the segregating heterozygotes.
These high animals are
You try to go
downwards, you pick
o.
out animals without the lethal and you mate it to itself, and of course
you get down.
If you try to go down any further your response will be much
lower, but in that generation you are picking out animals _hich do not
-73contain the lethal, so down you go with a bump.
So, there was a situation in which having taken it to pieces by the
usual heritability method one might have expected to resPOnd, we found
that it would in one direction and it would not in another, because it
had this lethal in,it.
Lastly, the low line, L-5.
I do not understhad it even yet.
Now, this really was a stinker, because
count was 3.7.
all.
The male count was 17.1, the female
There were a large number of females with no bristles at
It must have been very cold I should think.
The females were frightfully variable.
The distribution of females
looked something like this, going from zero to 20, there were a certain
number of zeros and there were some flies going up to 22 with a mean of
about 4.0, but there had been very little change in the female mean in
the last twelve generations.
The female mean had gone down from six to four in the last twelve
generations, so here we are again in a situation which we cannot get any
further by selection, but the population is fantastically variable.
We do some heritability estimates by our half-sib correlation and
we get an answer of 90_.
We do it by the full-sib correlations and we
get an answer for that of 60%.
We do it by daughter-dam regression, that
is to say we pick out the high females and low females and we get a very
low answer.
That is reasonable.
That is a replicate in a sense of what
we are doing in actual selection, and the offspring of the low females is
very little different from the offspring of the high females.
Going into this in detail, it turned out to be an exceedingly complex situation which we never got down to analyze properly because the
the Ph.D.
student who was doing the work decided he wanted his Ph.D.
and not to do any more work and I found myself shot away to look after a
farm for three months, so there we more or less stopped, but I think
-74•this would deserve more consideration.
As a complicated situation
which one might expect to hold very well for characters which are of great
importance to the animal, like fertility and egg laying and so on.
So, in these later generations, when we are dealing with a character
of considerable importance to the animal, which has been of importance to
it for twenty or thirty generations, our theory does break down.
Now, to generalize a bit, under what situations would one expect our
theory not to give us the right answer;in
response equal the expected response.
terms of will the prediction of
What sort of conditicns
in order for us to get our right answer?
must hold
Well, that entails an examination
of the conditions which must hold for the theory to be correct.
Now, I will list reasons why the theory would go wrong.
First of
all, if we had major genes segregating, I think we can expect the theory
to break down.
This may be in the sense of giving either a larger or
smaller response to selection than expected.
The theory is based on the
assumption of a large number of genes operating each with fairly small
effects.
When I say fairly small effects, in this particular population,
my standard deviation was 3.5-
I would expect the genes that were operating
to have an effect of about i, and then I would call that a mlnor gene.
If
major genes come into the situation at all, we will expect to get crazy
answers.
/
I may say that one major gene affecting this character did suddenly
pop into the population.
I gave the class to whom I was lecturing a popu-
lation to do some family selection, inbreeding and so on, just to show
theory
working in practice, and to my surprise it did not work at all,
because one of the inbred lines did not play the game and there turned out
to be a major gene segregating, which in females instead of having a mean
of 37 ha@ a mean of 84.
The females were sterile.
So even though they were
very high, I could not do anything about it because they would not breed
\
-75"
and I out-crossed them and all sorts of things to try to get rid of the
sterility and get a pure llne at that level, but no luck, so here again
is something which would be useful If only It _._as
not lethal or it was not
sterile in thls particular case.
The males would breed.
The second condition that must hold, the second situation In which
the theory will break down is if there is a great deal of natural selection, that is to say if the lethal genes are at all important in controlllng the situation.
In a population of cattle or of poultry, you might
have a lethal gene important and nevertheless not detected unless you were
specifically looking for it.
We had the lethals in our populations and we
only found them because we had specific methods of analysis which are only
possible in Drosophila.
The major gene I referred to earlier has got a mixture of natural
selection and a major gene put into It, but if natural selection is at all
important, I think we can expect that our heritabilitM estimates will not
be borne out in terms of response to selection.
ThirdlY, do complications such as epistasis enter into the picture
at all, so that perhaps they may require both Gene A and Gene B that Dr.
Lush mentioned thls morning.
Now, I do not myself see that such a situation would hold up selection.
t
On this I rather agree with Dr. Lush, one would eventually get to a situation in which you would fix both A and B and I think that in the process
of fixation your theory would give:vou reasonably the right answer about
what was going to happen.
I cannot see myself that epistasis is going to
complicate the issue very much as one i_ selecting.
Fourthly, will over-domlnance complicate it?
Here again -- I have
possibly not given this as much thought as I might, but I feel inclined to
give the answer probably not.
Now, there is a fifth reason; why you do not get the improvement that
-76you would think you ought to.
It is not really relevant to anything that
I previously said, but a situation in which the environment changes from
generation to generation.
Now, this could occur if disease is at all
important and if the pathogens that the flock is meeting in one year are
different from the pathogens that the flock are meeting in the next year.
One might see considerable heritable variation in the flock meeting
Pathogen A in a certainyear, one would select for it, but one would not
see any improvement in it next year because Pathogen A would not
be important and Pathogen B would. If that is at all important, I think
that might explain why we are not getting the response that we might.
Now, those five reasons to my mind pretty well include all the reasons.
There may be other reasons which I have not properly thought
about, but I put most of the emphasis therefore on the natural selection
and some on the possible occurrance of major genes.
There will be one great question mark in your mind, as there is in
mine, if these things can happen with Drosophila, what sort of experiment can we do with populations of cattle or with population of poultry
to make sure we are not in the same situation.
Now, I am not prepared to give an answer to that.
I would llke to.
I think that is what we must do in the next year or so perhaps, take some
of these populations which got into a peculiar situation, play all sorts
of tricks on them, inbreed them, select them, get heritabilities by dlfferent methods, do what I would call diagnostic experiments, see if one
can find out what is wrong without utilizing the tricks of Drosophila,
because quite obviously some of these populations superficially should
have responded to selection and we took them to pieces and we realized
why they should not, but it might have been difficult to take them to
pieces had they been populations of hens or populations of cattle.
I do not know whether I should Just throw in at the end of the possibility that some of these plateaus reached after long generations of
-77-
selection
can be br6ken
interest
lation
by mutation.
in the possibility
by mutation,
either
by spontaneous
is to the extent
quantitative
characters,
acter,
to be gleaned
which
would
ing, the amount
arising
is about
mutation
by x,radiation
population
broke
way,
through
experiments
this, which
up very
strikingly
much faster
Now, there are reasons
due to a crossing
matter
over happening
of operational
We have
variation
has been
fact,
irradiated
that we could
disappointing.
the controlled
we are used
inbred
more work along
place.
they took a
so I think
Thank
However,
through
it and
extent
has been
we must
you.
but
as a
by irradiation.
we could get new
have responded
those lines.
be an end.
There
of two genera-
and on the whole
lines, bnt the rate of response
I think that might
in which
and irradiated
was broken
lines
in
of new
that that was not mutation,
by selection
to in our populatlon,
to arise
of ten generations.
to see what
The irradiated
experiments,
at the moment.
in a matter
in a peculiar
it
the plateaus.
in Italy
for a matter
lines
utilize
minds
quickly
the plateau
it a figure,
of production
a plateau
for thinking
of variation
for very much
the rate
had reached
aris-
in the base population,
through
down
is
char-
variation
our selection
is in some people's
There
this particular
To give
we find
in these
nom-existent.
small.
with
of increasing
the plateau
tions and went
interfere
arises
or the amount
is very
of
into a popu-
of spontaneous
to let us break
interesting
like
variation,
amount
or by irradiation.
with
one could not hope
by mutation
are some quite
is almost
of the variation
the possibility
a certain
new variation
the amount
by mutation
not materially
the population
Now,
that
of spontaneous
and to put it another
mutation
out of some experiments
one-thousandth
so that would
to which
spontaneously,
suggest
spontaneously
has been
that one can get new variation
Our evidence
a little
There
much
our answer
faster
smaller
do considerably
than
than
•o78YOHE:
Do we have some questions?
DICKERSON:
I wonder if Alan would mind explainlng the difference in
a situation in which a homozygote is lethal but the heterozygote is better
than the homozygote.
ROBERTSON:
You mean explain the theory oF what would happen?
DICKERSON:
Well, if you discount the importance of over-dominance,
but_you say that this lethal situation is very important, I am a little
' confused.
ROBERTSON:
I knew this would cause an argument.
Well, a lethal
situation will behave like this, suppose one takes one's population here
and these are parents and you mate the extremes together, you mate high
to high, middle to middle and low to low.
Here we have the offspring and
experimentally and theoretically one gets this, this is _in which the heterozygote is greater than the homozygote.
Now, to my mind in theory if one was dealing with a situation with
genotype AIAI, A2A2, and AIA2 in order of preference and one got into a
balance between these two by selection, because this was higher than the
other two and one did the same thing, I am open to correction here and
probably will be, I would expect little response to back selection.
I
take it that the parent-offspring regression, over-dominance would be zero.
DICKERSON:
I fail to see the difference in definition between the
situations.
ROBERTSON:
In this situation we never see the animals aa at all,
they die.
DICKERSON:
That is right.
ROBERTSON:
I think the difference is that in one case you get no
response to back selection and in the other you do.
DICKERSON:
I guess I am a little dense.
ROBERTSON:
All right, we will fightlt
Nevermind,
out later.
go ahead.
-79-
FORBES ROBERTSON:
You drew an analogy between the situation in these
long selected lines and the genetic phenomena turned up withwhat
in characters that are more directly concerned wlthfltness;
happens
one of the
essential features of characters that are directly concerned with fitness,
as we all know, is great sensitivity to environmental conditions.
As you
know in the ordinary unselected stock, provided you do not starve your
animals, the bristle number is comparatively unaffected by the sort of
environmental variation which is very important say in butter fat production and so forth.
Now, what happened in the tall end of your selection, is there any
evidence of the environmental variation going up or not?
ROBERTSON:
Could we have the second slide?
You see What happens to the mean in different generations here, it is
pretty regular.
When we get down here it begins to wander about.
think we are finding the same phenomena there.
I
Certainly it is my impres-
sion with the low lines that they are much more sensitive to slight changes
of temperature or food or what have you.
I think we have the same thing
coming Inthere.
'
WARREN:
I have no question.
I have a comment that might bear on
this and I believe i am not giving away anybody's thunder, but in the laboratory at Purdue, where we have been carrying on selectiMe experiments,
one of Dr. Bells' students worked with a population that had a plateau
apparently for egg production and analyzed it for lethals and found little
or no evidence of lethals.
You are working here, of course, with a trait and whether that is Just
a peculiarity, I do _ot know_
_
ROBERTSON:
It might possibly happen that you would not get the same
thing with egg production and it might also be a function of the initial
population that we started with, which we know did have a fair number of
-8o-
lethals in it, as do most populations of Drosophila, but it was surprising
that so many of them seemed to have an effect on the bristle character as
well.
GOWE:
Dr. Robertson, did you ever take two lines, say two of your
high lines that were approximately the same mean and plateaued and mate
them together and see if you re-created your genetic variance?
ROBERTSON:
Yes, we did, but as far as I remember the mean changed
very little, that is to say we mated H-I and H-5 and it was more or less
intermediate and we then selected and we did not get a very striking
response on selection.
We got a little response, but I would not say
that _t was particularly greater than the slight remaining response in the
two individual lines.
GOWE:
Was that done with several lines or several crosses?
ROBERTSON:
It was done with the two _ighest lines, but_there are a
certain amount of theoretical reasons why in Drosophila you might find it
difficult to do that because you rely on crossing over to do it for you
and you have only got three chromosomes and so it might not be a very useful thing, one should not draw too many general conclusions from that.
In
any case, you might expect more response if the two lines were quite different in origin.
SHOFFNERi
What about the possibility, I suppose you call it a
physiological limit, in which you, after you are getting so many bristles
on a given space; unless you get bristles on the bristles, would that
make sort of a ceiling Situation for this?
ROBERTSON:
Well, a physiological limit I presume is a situation in
which genetic substitutions do not make any difference, that is putting the
physiologic thing in genetic terms.
Now, here we have a situation in which there are very considerable
genetic variations.
We Just cannot fix them.
Surely a physiological
-81-
limitwould
definition
bristles
you a population
whatever
genes
and you would
YOHE:
tainly
give
you put in, there
expect
Any further
recessed
Dr. S. S. Munro,
Chairman
THRUSDAY
pretty
well
first
describe
large group of outstanding
man,
and the second
a research
Dr. Munro
Wisconsin,
with
Hatcheries
personally,
He went wrong
down to the States.
the
He joined a
have in the States
that he went wrong
I can
here
from
is that he was a government
man, and he is now a commercial.
graduated
from McDonald
degree
gOvernment
Coop Hatcheries
College,
then went down
to Madison,
and then he has a lot in common
from Scotland
He then went back
the Canadian
Western
time
that arehere
in Scotland.
Coop.
I
SESSION
geneticists_.we
got his Master's
the fellows
P.M ....
him as a man twice gone wrong.
coming
I cer-
this afternoon.
o'clock
Western
EVENING
by
be anymore
of the group
Since many of you do not know Dr. Munro
time, he was a Canadian,
Canada,
SECTION
goingto
discussions
at four-thirty
beCause
to vary conslderably.
on behalf
for the excellent
PART Ill
HIGGINS:
Well,
variation,
arenot
such a population
questions?
thank you gentlemen
... The session
with very little
because
and worked
for about
he got hls Ph. D. degree
in Edinburgh.
fifteen
with
years
Then he worked
and Is now with
the
in Washington.
Dr. Munro.
MUNRO:
here
guess
Thank
you.
that I was brought
I have the distinct
from
the West
Coast
impression
to start
it is true that I used to do a lot of arguing,
quite a lot, physiologically
mine, the first
recognize
me.
who you were.
time I have
at least,
because
getting
a controversy.
hair
down
I
but I have mellowed
I met an old classmate
seen him for twenty-three
He sald If you kept a little
since
years
I think
of
and he did not
I would
have known
-SZ-
Some twenty years ago I got a little mixed up in what they now call
!'
population genetics and studied inheritance of egg production and was a
little bit surprised myselfto
find the figures I had at least seemed to
show that genetics was not very important and I published a paper or two
at that time.
It was hard work because I was at an institution which to
say nothing of not having an academic atmosphere had practically no library
facilities or no technical people to turn to and I had to dig all this
stuff out myself.
I was rather concerned then at that time because accord-
ing to figures I could gather there was not more than - I think I said 25%
heritability in egg production and I thought I was quite high because there
were a lot of things I could not remove from my data, like hatch date, which
made full sisters more alike than half sisters.
I do not think much thought
had been given to the subject, because that started quite a ruckus and a lot
of
dispute, most of which I never heard anything about until years after-
ward.
Now it is generally agreed that the figure is more likely lO%but
at that time I was expecially concerned, perhaps more concerned than most
with theoretical possibilities of what I called the gene to gene interaction
and the gene to environment interaction, which I mentioned in my papers.
For a long time I was an outcast in that regard, but I am commencing to feel
quite at home now, because we have this over-dominance and we have a recognition of eplstasis and we have these buffering genes now talked about and I
do not
have much to argue about, so my task is going to be quite easy here
tonight.
I Just have to introduce these people and tell you about their pedigree.
The first man on the program is Dr. Ed Godfrey.
This man was born in New
Hampshire, I guess he is a real New Englander, but he spent some time in the
Navy up there in the Artlc regions floating around and I am sure he got a
lot Of experience about buffering genes in sub-zero weather up there.
He has a Bachelo2's degree from New Hampshire, a Master's and a Ph.D.
-83!
at Ohio, then he spent one year at the University of Tennessee,.and then he
too went
commercial in 1953.
As far as his work is concerned, I think
most of you will recognize him from the work he did on the inheritance of
body welght in fowl and, also, thework
sex reversal in turkeys.
Dr. Godfrey.
he did on physiological basis of