Topic 1 - Cellular and Molecular Basis of Inheritance Flashcards
Revise and refresh ¥ DNA, packaging and chromosomes ¥ Gene structure ¥ DNA to RNA to protein ¥ Genetic variation
The beginning of life
Sperm fertilised egg cell (ovum) to form a zygote.
Ovum and sperm are haploid germ cells.
Zygote is diploid
Heredity
early scientists - hereditary characteristics transmitted by proteins.
1944 - bacteria work, DNA responsible
Why was there skepticism by the scientific community about DNA transmitting hereditary characteristics?
DNA was considered a very simple molecule - only 4 bases
Structure of hereditary material needed to be:
versatile to account for variety.
Be able to reproduce to form an identical replica
Structure described by Watson + Crick and Franklin + Wilkins fulfilled these requirements
Deoxyribonucleic acid (DNA)
- twisted double helix
- made up of 4 bases (chemicals)
Adenine and Thymine
2 H bonds
Guanine and Cytosine
3 H bonds
Bases are attached by
2 phosphate backbones
DNA is
tightly packed, takes up less space
How many bases in the whole human genome?
3.2 billion bases
DNA packaging chromatin =
DNA + RNA + protein
Main protein in chromatin are
histones
DNA wound around histones to form
nucleosomes
Nucleosomes organise into
solenoids
Solenoids
loop up into structure of chromatin (tightly packaged fibre)
Histones
DNA would round 2 each of histones H2A, H2B, H3 and H4
Histones core particles connected by a
short stretch of linker DNA, forming a structure resembling beads on a string
Histone 1 is NOT
part of the nucleosome bead
Histone 1 =
linker histone
Histone 1 binds to the
entry/exit sites of DNA on the surface of the nucleosomal core particle and completes the nucleosome
Types of chromatin
Euchromatin + heterochromatin
Euchromatin
open chromatin, prevalent in parts of the genome that’s being regularly used + in cells that are active in the transcription of many of their genes (active part of the genome)
Heterochromatin
condensed form of chromatin made up of tight loops, most abundant in parts of genome not in active expression + cells that are less/not active
Condensed DNA is packaged into
chromosomes
Human genome
22 autosomes + sex chromosomes
Human chromosome structure
2 identical chromatids, each contains 1 DNA molecule, centromere in middle.
Chromosomes vary in size, which is longest?
Chromosome 1
Genetic Makeup of Human cells Haploid
23 chromosomes: 1 copy of each autosome and 1 sex chromosome (X or Y)
Genetic Makeup of Human cells Diploid
46 chromosomes: 2 copies of each autosome 1-22 and 2 sex chromosomes (XX / XY)
Gene ->
Basic physical and functional unit of heredity
Gene is made up of
DNA, acts as instructions to make proteins
Genes vary in
length; few hundred bases - 2.5 million+
How many genes in the human genome?
20,000 - 23,000
Less genes in the human genome than expected, why?
due to alternative splicing
DNA to RNA to protein
- central dogma of molecular biology
- DNA to RNA - transcription
- RNA to protein - Translation
Each triplet codon codes a specific amino acid - non overlapping
- more than 1 codon per amino acid - degenerate code
Nonsense mediated control
?
Transcription
- RNA polymerase binds to a promoter sequence (near beginning of gene - directly/helper proteins)
- RNA polymerase uses the DNA template strain to make new/complementary RNA molecule (primary RNA)
- Transcription ends in termination (depends on sequences in RNA, STOP codon)
what is the main transcription enzyme?
RNA polymerase
RNA vs DNA
RNA - ss, uracil, less stable than DNA
RNA processing: before primary mRNA molecule leaves the nucles it’s modified:
Splicing (removing introns)
Capping (5’ end)
Polyadenylation (3’ end)
RNA capping
- 5’ cap added to 5’ end of newly synthesised mRNA using modified nucleotide 7-methylguanosine (to protect from degradation)
- capping occur after initiation of synthesis of mRNA and precedes other modifications that protect mRNA from degradation by RNases
closer look at 3’UTR
- 3’UTR begins at Translation Termination Codon
- part of mRNA and signals end of translation of the nucleotide code into a protein
- Polyadenylation of 3’ end occur before mRNA leaves nucleus
- 100-200 nucleotides long, protects mRNA from degradatory action of phasphatases + nucleases
- Export of mRNA from nucleus into cytosol relies on polyadenylation (adding of polyA tails)
Splicing
- Spliceosomal proteins bind to pre-mRNA template (has introns)
- Intron removed in the form of lariat and 2 exons ligated (spliced out) to make mature mRNA
Spliceosomal proteins
U1, U2, U4, U5, U6)