Transcript Topic 5 DNA, mutation and genetic variation study version

Heritable variation among
individuals
 Read Chapter 5 of your text
Heritable variation among
individuals
 Variation provides the raw material of evolution.
 Without variation there could be no selection because
there would be no differences to select for or against.
Discovery of genes
 Heredity was a big problem for Darwin because he
didn’t know how it worked.
 Darwin knew offspring resembled their parents, but it
was widely believed that heritability was a sort of
blending process akin to the way different paints can
be mixed to produce a new shade.
 The problem with blending inheritance is that a new
trait would be diluted in a large population and
disappear.
Discovery of genes – inheritance is
particulate
 Gregor Mendel (1822-1884) proved that inheritance is not a
blending process.
 Instead he showed that discrete particles (we now call them
genes) which remain intact through many generations carry the
hereditary information.
 An individual allele may sometimes be hidden in a generation
(e.g. a recessive allele as a heterozygote), but later reappear
intact in a later generation when present as a homozygote.
 Demonstrated this with his famous experiments using pea plants
(see box 5.2 pages 142-143 of the text or any introductory biology
text for a description of Mendel’s work)
Gene-centered thinking
 Different versions of genes, which we call alleles, are
the ultimate target of natural selection because they
can last for generations passing from body to body.
 Changes in population allele frequencies result in
evolution.
 Important to remember that individual bodies built by
genes are temporary assemblages of sets of genes.
Gene-centered thinking
 Individual organisms live and die. Each body (“survival
machine in Dawkin’s term from his book the Selfish
Gene”) is built by a temporary collection of genes
working together.
 Alleles that work well with others and help to build
well adapted bodies will become more common and
those that don’t will be disappear.
Gene-centered thinking
 To illustrate the idea of selection judging individual genes from
the products they build, imagine trying to select the best crew of
rowers for an 8-man boat from a large pool of potential rowers.
 By randomly making crews and racing boats against each other
and repeating the practice many time you would eventually
realize that certain rowers tended to be found more often in
winning boats and others in losing boats.
 Even though strong rowers would sometimes be in losing boats,
on average, they would win more often than weaker rowers.
Using the information on wins you could then build a very
strong crew.
 Similarly, genes that tend to build more successful bodies on
average would be favored by selection and spread.
Genes
 Mendel did not know what genes were, but we know
today that they are made of DNA and that they work
by coding the structure of proteins.
 Proteins are made of chains of amino acids joined
together and DNA dictates the identity and order in
which amino acids are joined together.
Structure of DNA
 DNA made up of sequence of nucleotides. Each
nucleotide includes a sugar, phosphate and one of four
possible nitrogenous bases (adenine and guanine
[both purines], and thymine and cytosine [both
pyrimidines]).
4.1a
4 + 4.1d
4.1b
.
Structure of DNA
 The opposite strands of the DNA molecule are
complementary because the strands are held
together by bonds between the opposing bases and
adenine bonds only with thymine and cytosine
only with guanine.
 Thus, knowing the sequence on one strand enables
one to construct the sequence on the other strand.
4.2
Structure of DNA
 The sequence of nucleotides in a gene codes for the
protein structure as each three nucleotide sequence
codes for one amino acid in the protein chain.
4.3a
Transcription and translation
 To make a protein the DNA must first be transcribed
into an RNA copy (called mRNA for messenger RNA)
and that mRNA translated into a protein or
polypeptide.
Production of protein from DNA requires
transcription and translation
Gene expression: process by which information from a gene is
transformed into product
Ribosomes translate mRNA into protein
One gene one protein
 The expression “one gene one protein” is widely used,
but most genes actually code for multiple proteins
because they join different “exons” the executable or
coding portions of a gene together to make different
proteins. This process is called alternative splicing.
RNA splicing can create multiple
proteins from a single gene
Mutations: creating variation
 A change in the structure of DNA, which may perhaps
result in a change in the protein coded for, is called a
mutation.
 Mutations are the ultimate source of all genetic
variation.
 A change to a gene can result in a new allele (version of
a gene) being produced.
Where do new alleles come from?
 When DNA is synthesized, an enzyme called DNA
polymerase reads one strand of the DNA molecule and
constructs a complementary strand.
 If DNA polymerase makes a mistake and it is not
repaired, a mutation has occurred.
Mutation and genetic variation
 Mutations are raw material of evolution.
 No variation means no evolution and mutations are
the ultimate source of variation.
Types of mutations
 A mistake that changes one base on a DNA
molecule is called a point mutation.
Examples of point mutations
Type of mutations
 A point mutation in a gene coding for the structure of
one of the protein chains in a hemoglobin molecule is
responsible for the condition sickle cell anemia.
Types of mutations
 Not all mutations cause a change in amino acid coded
for. These are called silent mutations.
 Mutations that do cause a change in amino acid are
called replacement mutations.
Types of mutations
 Another type of mutation occurs when bases are
inserted or deleted from the DNA molecule.
 This causes a change in how the whole DNA strand is
read (a frame shift mutation) and produces a nonfunctional protein.
Types of mutations
 There are multiple other forms of mutations that
involve larger quantities of DNA.
 Genes may be duplicated as may entire chromosomes
or even entire genomes.
 Genes may also be inverted.
Where do new genes come from?
 Mutation can produce new alleles, but new genes are
also produced and gene duplication appears to be most
important source of new genes.
Gene duplication
 Duplication results from unequal crossing over when
chromosomes align incorrectly during meiosis.
 Result is a chromosome with an extra section of DNA
that contains duplicated genes
4.7
Gene duplication
 Extra sections of DNA are duplicates and can
accumulate mutations without being selected
against because the other copies of the gene
produce normal proteins.
 Gene may completely change over time so gene
duplication creates new possibilities for gene
function.
Globin genes
 Human globin genes are examples of products of gene
duplication.
 Globin gene family contains two major gene clusters
(alpha and beta) that code for the protein subunits of
hemoglobin.
Globin genes
 Hemoglobin (the oxygen-carrying molecule in red
corpuscles) consists of an iron-binding heme group
and four surrounding protein chains (two coded for by
genes in the Alpha cluster and two in the Beta cluster).
Globin genes
 Ancestral globin gene duplicated and diverged into
alpha and beta ancestral genes about 450-500 mya.
 Later transposed to different chromosomes and
followed by further subsequent duplications and
mutations.
From Campbell and Reese Biology 7th ed.
Globin genes
 Lengths and positions of exons and introns in the
globin genes are very similar. Very unlikely such
similarities could be due to chance.
Exons (blue), introns (white), number in box is number of nucleotides.
4.9
Globin genes
 Different genes in alpha and beta families are
expressed at different times in development.
 For example, in a very young human fetus, zeta
(from alpha cluster) and epsilon (from beta
cluster) chains are present initially then replaced.
Similarly G-gamma and A-gamma chains present
in older fetuses are replaced by beta chains after
birth.
4.8
Gestation (weeks)
Post-birth(weeks)
Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin.
Enhances oxygen transfer from mother to offspring.
Chromosomal alterations
 Two major forms important in evolution: inversions
and polyploidy.
Inversions
 A chromosome inversion occurs when a section of
chromosome is broken at both ends, detaches, and
flips.
 Inversion alters the ordering of genes along the
chromosome.
4.10
Inversions
 Inversion affects linkage (linkage is the likelihood that
genes on a chromosome are inherited together i.e., not split
up during meiosis).
 Inverted sections cannot align properly with another
chromosome during meiosis and crossing-over within
inversion produces non-functional gametes.
 Genes contained within inversion are inherited as a set of
genes also called a “supergene”
Inversions
 Inversions are common in Drosophila (fruit flies)
 Frequency of inversions shows clinal pattern and
increases with latitude.
 Inversions are believed to contain combinations of
genes that work well in particular climatic
conditions.
Polyploidy
 Polyploidy is the duplication of entire sets of
chromosomes.
 A polyploid organism has more than two sets of
chromosomes.
 E.g. A diploid (2n chromosomes) organism can
become tetraploid (4n), [where n refers to one set of
chromosomes].
Polyploidy
 Polyploidy is common in plants, rare in animals.
 Half of all angiosperms (flowering plants) and almost
all ferns are polyploid.
Polyploidy
 Polyploidy can occur if an individual produces diploid
gametes and self-fertilizes generating tetraploid
offspring.
 If an offspring later self fertilizes or crosses with its
parent, a population of tetraploids may develop.
FIG 4.12
Polyploidy
 If a sterile plant undergoes polyploidy and self-
fertilization a new species can develop essentially
immediately.
Polyploidy
 Cross-fertilization of different species, followed by
polyploidy, was responsible for the development of
many crop plants e.g. wheat.
 Initial cross-fertilization produces sterile offspring,
because chromosomes cannot pair up during
meiosis.
Polyploidy
 Triticum monococcum (AA) X wild Triticum (BB) cross
produced sterile hybrid with 14 chromosmomes (AB; 1-7A
and 1-7B). {capitalized letters symbolize species source of
chromosomes, number denotes individual chromosome
e.g. 1A, 3B}
 Polyploidy of first sterile hybrid produced Emmer Wheat T.
turgidum (AABB) which has 28 chromosomes. Emmer
Wheat isn’t sterile. It has two copies of each chromosome
(e.g. two 1A chromosomes, two 3B chromosomes, etc.).
Polyploidy
 Further cross between Emmer Wheat and T.
tauschii which has a total of 14 chromosomes (DD)
produced a sterile hybrid with 21 chromosomes
(ABD).
 Further polyploid error in meiosis produced T.
aestivum Bread Wheat with 42 chromosomes
(AABBDD). Those chromosomes are derived from
3 ancestral species.
Mutation rates
 Most data on mutations comes from analysis of loss-
of-function mutations.
 Loss-of-function mutations cause gene to produce a
non-working protein.
 Examples of loss-of-function mutations include:
insertions and deletions, mutation to a stop codon and
insertion of jumping genes.
Mutation rates
 Some mutations cause readily identified phenotypic
changes.
 E.g. Achrondoplastic dwarfism is a dominant disorder.
An achrondoplastic individual’s condition must be the
result of a mutation, if his parents do not have the
condition.
Mutation rates
 Human estimate is 1.6 loss-of-function
mutations/genome/generation.
 A comparison on the entire genomes of two
human children with their parents resulted in an
estimate of 70 mutations per child.
Other sources of genetic variation
 A very important source of variation in offspring results from
sexual reproduction.
 During sexual reproduction new chromosomes are produced
during the process of meiosis (gamete formation) in which
homologous chromosome exchange segments of DNA.
 In addition, homologous chromosomes independently assort
into gametes so unique combinations of chromosomes occur in
each gamete
 Finally, the merger of sperm and egg brings together new
combinations of chromosomes.
Independent
assortment
ensures novel
combinations of alleles
The link between genotype and
phenotype
 The genetic makeup of an individual is its genotype.
 The physical appearance of an individual is its
phenotype.
Simple genetic polymorphisms
 The traits Mendel studied (fortunately for him) were
simple, discrete traits that were controlled by single
genes.
 When the link between genotype and phenotype is so
simple and direct it is easy to see how genotype affects
phenotype.
 For example, alleles of a single gene controls leaf shape
in the ivy-leaf morning glory
Simple polymorphisms can
produce differences in phenotype
Simple genetic polymorphisms
 Similar simple genetic polymorphisms result in various
diseases of humans.
 Sickle cell anemia, Tay-Sachs disease and Huntington’s
Disease are all homozygous recessive disorders
(someone with two copies of the disease-causing allele
develops the disorder, heterozygotes and homozygotes
for the “normal” allele do not.)
Quantitative genetic traits
 Most traits however are not under such simple direct
control of one or a few genes.
 Traits, such as height, do not exhibit discrete
categories. Instead variation is continuous.
 The continuous variation is the result of differences in
genotypes where there many genes contribute to the
value of a trait.
Quantitative traits influenced by
multiple genes
Francis Galton (1822-1911)
Quantitative traits influenced by multiple
genes; generate a normal distribution
Environmental influences on
phenotype
 The environment also plays a role in quantitative
values of traits.
 Environmental influences can be factors such as food,
but a genes environment includes the activity of other
genes, which may influence how much or even
whether a gene is expressed.
 Traits differ in their degree of phenotypic plasticity.
Height can be strongly influenced by diet, but our
number of eyes is not.