LECTURE 1.

Overview & History of Quantitative Genetics

most of the traits studied by whole organism biologists are encoded by a
large number of genetic loci, and for practical reasons the individual loci are
generally unobservable
Thus, the single locus theory that is used in population genetics theory to
illustrate, for example, the Hardy-Weinberg law, is not very useful.
In Quantitative Genetics, most final formulations are in terms of
phenotypic means and variances, because such measures are accessible,
while the loci themselves are not.
What, then, is Quantitative Genetics? A statistical branch of genetics
based upon fundamental Mendelian principles extended to polygenic
(multilocus) characters.
The main principles of Quantitative Genetics were outlined by R. A. Fisher
and Sewall Wright, whose work had implications outside the field of
genetics.
Fishers work on partitioning variation led to the ANOVA, and he laid
extensive groundwork in experimental design and hypothesis testing.
Wrights work with path analysis was widely used in the social sciences.
Our text notes that Quantitative Genetics theory was eagerly embraced by
plant and animal breeders, but there was a 50 yr lag phase before
evolutionary biologist began to apply Quantitative Genetics analyses to their
research. This was interesting in light of the fact that Wright and Fisher
were evolutionary biologists.
The goal of the text is to bring together diverse results of Quantitative
Genetics that have developed semi-independently in evolutionary biology,
animal breeding, plant breeding, and human genetics. Although this course
will always adopt the approach of using Quantitative Genetics to facilitate or
better understand plant breeding, we will utilize results and insights from
these other disciplines where appropriate.

 Today, at the beginning of the 21st century, Quantitative Genetics is often

regarded as outdated and/or useless. Two refreshing points are made in our
text in connection with this perspective: 1. Many key results from animal
and plant breeding experiments have been shunned by evolutionary purists;
2. Despite criticisms of molecular biologists molecular analysis is not
necessary of even useful for: explaining patterns of resemblance between
relatives, shifts in phenotypic means and variances, or explaining constraints
on joint expression of correlated traits.
Historical background
Galton Founded the Biometrical school focus on traits showing
continuous variation vs. the Mendelians led by Bateson, where the focus was
on the inheritance of discrete traits.
The Big Question: Do discrete Mendelian traits have the same hereditary
and evolutionary properties as contiuously varying traits?
Issues: Intermediacy of phenotypes
Darwin assumed continuous traits would show a blending
inheritance. The problem with this theory is that half of the
observable variation would disappear each generation, so it required
the synthesis of large amounts of new variation.
Galton, Darwins cousin, studied parent and progeny heights. When
plotted against one another, a linear relationship was observed, but the
progeny were less exceptionial than the parents. Parents shorter than
the population mean had progeny taller than themselves but still
shorter that the population mean. Galton referred to this as
regression toward mediocrity and said it would erode away
selective progress.

Pearson pointed out the flaw in Galtons thinking. If parents taller

than the mean mated, progeny would not be shorter than the
population mean. The progeny would be shorter than the selected
parents, but taller than the population mean. Galton didnt realize that
the progeny generation start from a new mean each generation.

Note that the response to selection is s 0, where s is the mean of the

selected parents and 0 is the mean of the offspring of the selected parents.
The new mean height is stable, it will not regress if selection stops. Thus,
natural selection could be explained as a force in evolution. Pearson
developed many of the regression tools that are so widely used today.

Multi-factor hypothesis
Mendel himself suggested a mechanism for explaining the maintenance of
genetic variation: that continuous variation was really due to segregation of
multiple factors. However, the Mendelians did not accept this.
George Shull, a corn breeder shed some light on this when he observed that
inbred lines derived from a heterogeneous, heterozygous population were
much more uniform within themselves than was the population from which
they had been derived. This observation led to the conclusion that the genes

which conditioned the quantitative variation must in fact be Mendelian

genes.

Nilsson-Ehle's experiment on wheat seed colour

H. Nilsson-Ehle, a Swedish geneticist and wheat breeder, reported in 1908
on the results of crossing wheat cultivars with different seed colors.
-----------------------------------------------------------------------In a cross between a white-seeded cultivar and a cultivar with very dark red
seeds, the F1 plants had medium-red seeds but the F2 showed apparently
continuous colour variation, from white to very dark red.

Nilsson-Ehle was able to classify the seeds into 5 colour classes:

*
white
*
light red
*
medium red
*
dark red
*
very dark red
and then show that the genetic ratio fit what would be expected for 2 loci
with additive effects.

Later, he found a 3rd locus for seed color. In an F2 generation segregating

for all 3 loci, 1/64 of the plants would have white seeds.

Nillson-Ehles conclusions: 1. Sexual reproduction unleashes tremendous

genotypic diversity; 2. Apparently new types appearing in a population may
be rare segregants rather than new mutations.
East and Emerson: Conducted numerous experiments with plants in which
two diverse inbred lines were crossed. They observed an outbreak of
variation in the F2. This trend was completely in line with the Mendelian
model, but did not agree at all with the blending hypothesis.
The Role of the Environment
W. Johannsen, a Danish botanist reported in 1903 on a selection experiment
on seed size in bean (Phaseolis vulgaris), a self-pollinated crop.
Note: Johannsen did his work before Mendel's laws were re-discovered.
-----------------------------------------------------------------------Johannsen started with a variety called 'Princess'.
(Like most other self-pollinated varieties of that time, 'Princess' was a
heterogeneous mixture of highly homozygous lines.)

He observed variation in seed size.

This variation would have been due to:

*
genetic variation among the component lines of the variety

environmental variation

He selected seeds of different sizes.

He grew their progeny & compared the weight of each seed to the weight of
its progeny.

The progeny from small seeds tended to have smaller seeds than the progeny
from large seeds, but there was still variation within each line.
Within each line, he selected small and large seeds & grew their progeny.

There were still differences AMONG lines for seed size, but there was NO
further response to the selection WITHIN lines. Variation for seed size in the
progeny lines was similar to the variation in the parental lines.
Explanation: Johannsen's initial selection for different seed sizes isolated
some of the component lines of 'Princess' bean. These lines had inherently
large or small seed size, but since they were already homozygous, selection
within them was not effective. All of the within-line variation that
Johannsen observed was all due to environmental effects.
Conclusion: A mixed population of a self-pollinated crop species can be
separated into inherently different pure lines, but further selection within
those lines is ineffective.
-----------------------------------------------------------------------Johannsen's pure-line experiment demonstrated that:
*
quantitative variation can have a genetic component
*
the distinction between genotype and phenotype
*
selection within pure lines is ineffective
but it did not explain how quantitative traits are inherited.
Johannsen coined the terms genotype (denotes genetically identical
members of a pure line) and phenotype (observed value for an individual
a composite of genetic and environmental effects).
Johannsen concluded that natural selection could never move a character
value beyond the level of variation seen in the original population. Like

Galton, he felt that major mutations were required to generate the variation
needed to drive evolution.
In 1918, Payne showed that selection on Drosophila bristle number resulted
in flies with more extreme phenotypes than were observed in the base
population. This was and is a function of gene frequency. At intermediate
frequencies, the frequency of the 10 locus homozygote, for example, is 1 in
a million. At a gene frequency of 0.9 for the favorable allele, however, this
frequency is 0.12. Thus, as selection increased the frequency of certain
alleles, the likelihood of seeing extreme phenotypes was increased.
The Major Goals of Quantitative Genetics
1. How much of the observable variation in quantitative traits is due to
genetic factors and how much is due to environmental ones?
2. Improved understanding of the types of genetic variation that exist
and their relative importance.
3. Understanding of the molecular basis of mutations in quantitative trait
loci.
4. The role of nonadditive gene action in the expression of quantitative
traits.
5. Extent to which alleles at different loci are distributed independently
vs. being associated statistically.
6. Mechanism by which gene action maps developmentally into
phenotypic expression.