Download TT2007 Lecture 8 HB

BIOLOGICAL CHEMISTRY
Prof. J.H.P. Bayley, Dr. R.M. Adlington and Dr. L. Smith
Trinity Term 2007 - First Year
Lecture 8
Hagan Bayley
Introduction to genetics and the machinery of
protein synthesis. Genotype and phenotype,
Mendelian genetics, dominant and recessive
genes, chromosomes, genetic maps, genome
sequencing. [HB]
Hartl, D. L. and E. W. Jones,
2006 Essential Genetics.
4th ed. Jones & Bartlett,
Sudbury, MA. 600 pp.
3rd ed
Lecture notes are at:
www.chem.ox.ac.uk/bayleygroup/
on weblearn soon
Nucleus
Genes arranged on chromosomes
Site of chromosome replication
Site of synthesis of mRNA, which
codes for proteins
Ribosomes are made in the nucleolus
Regulatory factors & gene products
transported in and out via nuclear
pores
The space between the two nuclear
membranes (the "perinuclear space")
is continuous with the lumen of the
rough endoplasmic reticulum (RER)
Genotype and phenotype ...
Genotype- the genetic constitution of
an organism (or cell), i.e. the nature of
the organism's genome.
Phenotype- The observable properties
of an organism (or cell), which result
from the interactions of the genotype
and the environment
Chromosomes
• genes are organized in chromosomes- 46 in humans
• in eukaryotes, chromosomes are very long linear
sequences of double-stranded DNA (encased in
proteins including histones)
• 23 pairs (sets) of homologous chromosomes in
diploid cells- one in each pair from father, one from
mother
• germ cells (gametes: sperm cells and eggs) are
haploid - 23 chromosomes, one from each set
Genetic maps and genome
sequencing
• until recently genes were painstakingly
mapped to specific chromosomes and
ordered within each chromosome (genetic
map)
• now the entire sequence of every
chromosome of the human genome is
available- rough sequence 2001, by now
highly refined
Human genome
Each position 2 bits: 22 = 4 bases
Human diploid genome: 6 X 109 bases
12 X 109 bits = 1.5 X 109 bytes = 1.5 Gb
… or the number of letters in 1000 long novels; there are
660,000 words in War and Peace …
Storage space of CD 700 Mb
Would fit, with error correction, on a single DVD (4.7 Gb)
Genetic variation
• We are all "mutants"- variations in our genes have arisen
through the generations
allele- any one of the alternative forms of a gene
• gene chips and rapid re-sequencing for mutational analysis,
e.g. for forensic or medical applications
cell cycle and somatic (non-germ) cell division
mitosis- all 46
chromosomes
replicated in each of
the two progeny
cells. DNA is
replicated
(chromosomes are
duplicated) before
nuclear division
starts
this organism has
two pairs of
homologous
chromosomes red/
orange and green/
blue
meiosis- DNA is replicated
(chromosomes are
duplicated). There follow two
successive cell divisions with
no further replication to yield
four haploid cells (each
contains one copy of each of
the 23 chromosomes). The
chromosomes (and their
associated variations- alleles)
are randomly assorted during
this process.
This is the basis of Mendelian
inheritance
illustrated for just one pair of homologous chromosomes
crossing over/ recombination
occurs during meiosis leading to the occasional re-assortment
of genes between members of homologous pairs of
chromosomes- an additional source of genetic variation
Types of mutation
produces allelic variation
• molecular basis of mutation
base substitution
base deletion
base insertion
• effects of mutation
silent (degenerate code) UCCUCG, SerSer
missense GAGGUG, GluVal (sickle cell disease)
nonsense (termination) UACUAG, TyrSTOP
frameshift
Genetic code- three base codons … at least one for each
amino acid (degenerate code)
Genetic diversity
• mutations are redistributed by:
chromosome re-assortment- in meiosis
crossing over (recombination)
• fertilization brings together 23 chromosomes from
each gamete- sperm and egg to produce a 46
chromosome zygote
Gregor Mendel- genes come in pairs, separate in gametes,
and randomly come back together again as pairs during
fertilization. This is explained in modern terms by reassortment during meiosis
allele- any one of the alternative forms of a gene
homozygous organism- organism having the same allele of a
gene on the two homologous chromosomes
heterozygous organism- carrying dissimilar alleles of a
gene(s); not homozygous
dominant trait- if an allele is present in a heterozygous
genotype, it results in a phenotype characteristic of the allele
recessive trait- refers to an allele that results in a
characteristic phenotype only in the homozygous genotype
XY sex chromosomes are an exception to rule
of homologous pairs
Technologies
DNA microarrays
• spotted
• in situ synthesis
DNA sequencing
ddCTP
ddTTP
analog