The Molecular and

Chromosomal Basis of
Inheritance
30 January 2014
ISB 202

How does inheritance work?

Overview

DNA is replicated precisely by mitosis in body

cells, which have 2 sets of chromosomes
Individuals make sex cells

single set of chromosomes (molecules of DNA) apportioned to

each sex cell by meiosis
In meiosis, different gene forms (alleles) assort randomly
And, alleles for different traits assort independently
Plus, some mixing of mothers and fathers DNA (crossing over)

Sex cells unite in fertilization

Fertilized egg now has double set of chromosomes
One set each from mother and father

Genes are segments of DNA on chromosomes

that direct development of individual traits
Different alleles may code for different versions of traits
E.g. blue eyes vs. brown eyes

DNA
DNA is the genetic material of all living
organisms
Nucleic acid
Inherited from parents
Precisely replicated
some mistakes
recombination

Directs its own replication

Heredity information encoded in chemical language
Reproduced in nearly all cells of body
Directs development and maintenance of virtually all traits

Hierarchy---organism to
nucleotide
The
human
body
contains
about 100
trillion
cells.

There is a
nucleus
inside
each
human cell
(except red
blood cells).

organism cells

Each
nucleus
contains 46
chromosomes,
arranged
in 23
pairs.

One
chromosome
of every
pair
is from
each
parent.

chromosomes

The
chromosomes
are filled
with tightly
coiled
strands
of DNA.

Segments of DNA
genes
nucleotides
GT AC

G
A T

Composition of DNA
DNA a molecule with three components
Nitrogenous base (4)

Adenine (A)
Thymine (T)
Guanine (G)
Cytosine (C)

A sugar, deoxyribose
A phosphate group

1 base + 1 sugar + 1 phosphate = one

nucleotide
DNA chain (nucleic acid) made up of many
nucleotides
Sugar and phosphate ALWAYS the same
Uracil (U) only in RNA

Nitrogenous bases
Different species differ in amount of four nitrogenous
bases
But: number of A = T, number of C = G
Proportions of A+T and C+G differ

Nitrogenous bases always pair in specific

combinations
A+T
C+G
Always 1 purine + 1 pyrimidine
A and G are purines
C and T are pyrimidine's

DNA structure
Base-pairing rules:
C with G, A with T

From one strand, can know

sequence of nitrogenous
bases in other
(complementary) strand
C-G-T-A on one strand
G-C-A-T on other

Linear sequence of bases

almost infinitely variable
2.9 billion base pairs in
human genome

Consequences of
base-pairing rules
Allows for sequential replication
DNA is pair of complementary templates
Prior to duplication, chains unwind and
separate into strands
Each strand acts as template for new,
identical strand which becomes chain

Each of two daughter molecules has one

old and one new strand
Semiconservative replication

DNA replication
Principle elegantly simple
Remarkable in speed and complexity
Takes a few hours for human cell to copy its
6 billion bases
About 1 uncorrected mistake per billion
nucleotides (1/10,000 before correction)
Mutation
If in sex cells, can be passed on to offspring

Over a dozen enzymes and other proteins

participate
Fundamentally similar in all organisms

Then what?
DNA is the code that directs protein synthesis
Proteins give cells shape and control chemical
reactions in and between them
C.100,000 different proteins in humans

All important, many necessary, in right quantities and

places
Defense
Immune system

Transport
Enzymes
Cause reactions to happen

Signaling
Structure

How does a gene specify a protein?

DNA does not directly catalyze protein
formation
Its ONLY an information storage molecule

RNA is the intermediary

Like DNA except:
Thymine replaced by uracil (U)
Sugar deoxyribose replaced by ribose
Single-stranded

Transcription
First major step in converting
genetic information into
proteins
Process by which messenger
RNA (mRNA) is made from
DNA template
In the cell nucleus
mRNA is a copy of one DNA
strand but with U instead of T

Translation
Second major step: translation
Process by which proteins and
peptides (protein building blocks) are
synthesized from mRNA
Read by ribosome in cell cytoplasm
3 nucleotides at a time = codon
Most codons specify a particular amino
acid (AA)

Proteins made up of chains of AAs

Fold into distinctive structures

Genes to chromosomes
Genes are stretches of DNA lined up lengthwise
Many genes in one chromosome
Many nucleotides per gene
Each gene codes for different things
Functional units

Humans have 23,000 distinct genes

DNA Normally uncondensed

Condenses into chromosomes for cell division
Mitosis, meiosis

Humans have 23 pairs of chromosomes, 46 total

A duplicate set of each with same genes, one chromosome set
from each parent
Other organisms have different numbers

Meiosis vs. Mitosis

Mitosis is division of cell nuclei that results in two daughter
nuclei that are genetically identical to parent
No variation produced
For growth and cell replacement
Both parent and daughter cells have 2 copies of each chromosome
(23 pairs, 46 total in humans)
Each chromosome is one condensed DNA molecule

Meiosis is nuclear division in which parent cell with 2

copies of each chromosome produces daughter cells with 1
copy each
Much variation produced
Takes place in sex organs prior to formation of eggs and sperm
Eggs and sperm formed from cells that have undergone meiosis
So, when egg is fertilized by sperm, the organism formed has the right number or
chromosomes

Why study meiosis?

Responsible for much variability among
individuals
Determines who gets what parental features

Underlies evolution of sexual reproduction

Why do so many organisms undertake the costly
process of sex?
Must produce twice as many offspring as asexual reproduction
Must spend much energy on mate attraction

Meiotic mistakes may result in spontaneous

abortion, abnormalities

Sexual reproduction
Egg and sperm (gametes or sex cells)
whose genetic contents determined by
meiosis unite
Fertilization
Forms a new individual
Eventually an embryo, then adult

Irish Elk

Sex employed in a minority of

organisms
Some never
Some rarely
But sex drives evolution of many organisms

Gametes defined by relative

sizes:
Male sperm small, female egg large

http://www.arkive.org/blue-bird-ofparadise/paradisaea-rudolphi/video-00.html
http://www.arkive.org/superb-bird-ofparadise/lophorina-superba/video-00.html

Superb
Bird-of-Paradise

Some gene terminology

Gene:
section of DNA that influences one or more
hereditary traits (characteristics)

Homologous chromosomes:
Matching maternal and paternal

Alleles:
versions of same genes that may code for
differences in traits on homologous
chromosomes
(= homologs)
Homologs carry same genes but may have
different versions
If versions dame, homozygous
If different, heterozygous

Overview of Meiosis
Each chromosome
copied (replicated)
before meiosis
then has two joined
sister chromatids
One homologous pair of
maternal chromosomes
(from mother), one pair
of paternal (from father)

Overview of
Meiosis (cont.)
Two consecutive cell divisions, meiosis I and
II
Homologs separate in meiosis I
Sister chromatids separate in meiosis II

One cell with 2 copies each of maternal AND

paternal chromosomes (after DNA
replication) becomes 4 cells each with just 1
uncopied maternal OR paternal chromosome
These then become gametes (eggs, sperm)

Consequences of
Meiosis
Random assortment of maternal and
paternal chromosomes (23 each) produces
many possible combinations
2n = 223 = 8,400,000 in each human gamete
8.4 million x 8.4 million genetically distinct
possibilities from any one human mating (egg
+ sperm)

Crossing over makes variation almost

Crossing over:
infinite
exchange of
genes
between
maternal and
paternal
chromosomes

Meiosis across
organisms
Essentially the same process in all sexually
reproducing organisms
Occurs at vastly different times in
organisms life cycles
Timing of events varies
Extent of each stage varies
E.g. most animals (like humans) are diploid (not
required), with two copies of each chromosome
except as eggs and sperm
Plants and many simple organisms have extended
haploid stages, with one copy of each

Sex in a nutshell
So, why did sexual
reproduction evolve and why
is it maintained?
Creates near-infinite variability

Why is variability important?

By chance, some offspring will
be best suited for changing
environment
E.g., climate
Parasites
Predators

Mistakes in Meiosis
For a gamete to receive one complete set of
chromosomes, homologous chromosomes must
separate in Meiosis I and sister chromatids must
separate in Meiosis II
Often dont, especially in Meiosis I
C.10% of the time
Usually results in spontaneous abortion

Nondisjunction
Down syndrome
Trisomy 21

Why do offspring
resemble their parents?
Long one of the major questions in
biology
Partly answered in 1865 by Gregor Mendel
Austrian monk

Partly by description of meiosis in late 19 th

C

Two parts linked by chromosome

theory of inheritance (1903)
Meiosis causes Mendelian patterns of
inheritance
Principle of Segregation: when any individual
produces gametes, gene copies separate so
each gamete receives only one copy

Mendel

What did Mendel do?

Crossed garden peas with different
traits from pure-breeding lines
E.g., green, round with green,
wrinkled

What did Mendel find?

First generation

Second generation

So: in first generation offspring, no wrinkled seeds

BUT: of seeds in 2nd generation wrinkled

Mendels conclusions
Individuals have different alleles
Different forms of same gene

Alleles in an individual are its genotype

Genotype affects phenotype (manifestation
of traits)
Double alleles allow for dominance and
recessiveness
recessives are masked by dominant alleles if they occur
in same organism

Alleles dont blend together

Heterozygotes show dominant trait
Only homozygous recessives show recessive trait
1:2:1 genotypic ratio, 3:1 phenotypic ratio

Two main rules

of genetics
Types and proportions
of progeny explained by
1) Law of Segregation:
For each chromosome type (=number), offspring end
up with one copy of either paternal or maternal
chromosome

2) Law of Independent Assortment

If different genes are on different non-homologous
chromosomes, they are inherited independently

But, many exceptions/complications!

Following slides

Exceptions to Mendelian
Genetics
All the preceding followed Mendelian
Genetics

Incomplete dominance
With incomplete
dominance, heterozygotes
look intermediate between
two different homozygotes
Produces third phenotype
that blends parental
phenotypes
But still have original
phenotypes in homozygotes
NOT blending inheritance!

Codominance
Heterozygotes have phenotype of both alleles
Phenotype expresses both alleles

Roan coat in horses, cows

Some hairs are red, some are white; mixed
together

Multiple Alleles
Most populations have many alleles at a
given gene locus
E.g. hemoglobin in humans
>500 known different alleles
Many result in distinctive phenotypes
Normal, reduced, or heightened oxygen-carrying
capacity
E.g., adaptation to high altitudes
Resistance to malaria parasites
Susceptibility to anemia

Polymorphic traits
When multiple alleles produce more
than two distinct phenotypes
E.g. oxygen-carrying capacity in humans
E.g. ABO blood types

Pleiotropy
Single gene affects multiple
different traits
e.g., yellow coat color in lab mice
Heterozygote has yellow coat
Homozygote dieslethal gene

Environmental effects
Genetic effects control nearly all
phenotypic traits
But environmental effects also important in
many
E.g., poor diet results in shortness
Lack of vitamin A results in poor eyesight