代写代考 A hopefully not-too-scattered primer in genetics (part 1)

A hopefully not-too-scattered primer in genetics (part 1)
F ́abio H. K. Mendes, Ph.D.
The University of Auckland
March 8, 2019

This is how I felt preparing this lecture

The importance of genetics for us is two-fold

The importance of genetics for us is two-fold
1. The genetic material determines what organisms look like.

The importance of genetics for us is two-fold
1. The genetic material determines what organisms look like.
2. It “records” evolutionary history as it is passed down through
generations and timescales.

1. The genetic material determines what organisms look like
1.1 The nature of the genetic material
1.2 The central dogma of molecular biology
1.3 Mutation introduces variability into a population of organisms 1.4 Genes, alleles, genotypes, phenotypes
1. The genetic material determines what organisms look like (3/38)

The genetic material does not just float all over the place
1. The genetic material determines what organisms look like (4/38)

The genetic material does not just float all over the place
􏰁 This is for organisms that have cells with a nucleus (eukaryotic organisms). Bacteria do not have a nucleus and so their DNA is not compartimentalized (prokaryotic organisms).
1. The genetic material determines what organisms look like (4/38)

The genetic material does not just float all over the place
􏰁 Many different type of proteins keep DNA highly compacted. Histones, for example, are very conserved evolutionarily.
1. The genetic material determines what organisms look like (4/38)

The genetic material does not just float all over the place
􏰁 Chromosomes as you would draw them are only observed when
DNA is super condensed.
1. The genetic material determines what organisms look like (4/38)

The genetic material does not just float all over the place
􏰁 The metaphase chromosome happens during mitosis and is the most highly compacted form DNA can attain.
1. The genetic material determines what organisms look like (4/38)

The genetic material does not just float all over the place
Metaphase chromosomes (human karyotype).
1. The genetic material determines what organisms look like (4/38)

“Genome” refers to the whole set of chromosomes in a living cell, organism or species
1. The genetic material determines what organisms look like (5/38)

“Genome” refers to the whole set of chromosomes in a living cell, organism or species
􏰁 A genome is said to be diploid (2N chromosomes) when there are two sets (mom & dad) of every different chromosome.
􏰁 Genomes can be haploid (N chromosmoes) if there is just one set (like in our gametes), tetraploid, octaploid, etc.
1. The genetic material determines what organisms look like (5/38)

DNA is a double-stranded nucleic acid
􏰁 DNA is a macromolecule comprised of five elements that organize themselves in subunits called nucleotides.
1. The genetic material determines what organisms look like (6/38)

DNA is a double-stranded nucleic acid
􏰁 Nucleotides are made up of a sugar (deoxyribose in DNA), a phosphate group, and a nitrogenous base.
1. The genetic material determines what organisms look like (6/38)

DNA is a double-stranded nucleic acid
􏰁 There are four different nitrogenous bases in DNA: adenine (A), cytosine (C), guanine (G) and thymine (T).
1. The genetic material determines what organisms look like (6/38)

DNA is a double-stranded nucleic acid
􏰁 Bases A and G are purines (class of organic compounds), C and T are pyrimidines.
1. The genetic material determines what organisms look like (6/38)

DNA is a double-stranded nucleic acid
􏰁 In DNA, adenine pairs up with cytosine (A=T), and cytosine with guanine (C≡G).
1. The genetic material determines what organisms look like (6/38)

Nucleic acid strands have directionality
􏰁 The 5’ (“five prime”) end has a phosphate in the 5th carbon. The 3’ end (“three prime”) has a -OH in the 3rd carbon.
1. The genetic material determines what organisms look like (7/38)

Nucleic acid strands have directionality
􏰁 The two strands in a DNA molecule are antiparallel. 1. The genetic material determines what organisms look like (7/38)

RNA is a single-stranded nucleic acid
􏰁 RNA differs from DNA in that its sugar is a ribose (has an extra -OH), and it does not have thymine, but uracil instead.
1. The genetic material determines what organisms look like (8/38)

DNA synthesis
􏰁 Synthesis of DNA happens during mitosis and meiosis.
1. The genetic material determines what organisms look like (9/38)

DNA synthesis
􏰁 Synthesis of DNA happens during mitosis and meiosis.
􏰁 In multicellular eukaryotes, somatic cells (skin, muscles and organ tissues, stem cells) undergo mitosis.
􏰁 Reproductive cells undergo meiosis.
􏰁 DNA replication is semiconservative.
1. The genetic material determines what organisms look like

DNA synthesis
􏰁 Synthesis of DNA happens during mitosis and meiosis.
􏰁 In multicellular eukaryotes, somatic cells (skin, muscles and organ tissues, stem cells) undergo mitosis.
􏰁 Reproductive cells undergo meiosis.
􏰁 DNA replication is semiconservative.
􏰁 Nucleotides are always added to the 3’ end of the new strand by the DNA polymerase enzyme.
1. The genetic material determines what organisms look like

Movie recommendation
’s Gattaca (1997), Columbia Pictures 1. The genetic material determines what organisms look like (11/38)

The eukaryotic gene
1. The genetic material determines what organisms look like (12/38)

Transcription: DNA (genes) to RNA
1. The genetic material determines what organisms look like (13/38)

Transcription: DNA (genes) to RNA
􏰁 Transcription happens in the cell nucleus (in eukaryotes).
1. The genetic material determines what organisms look like (13/38)

Transcription: DNA (genes) to RNA
􏰁 Transcription happens in the cell nucleus (in eukaryotes).
􏰁 As in DNA synthesis, the new RNA strand grows from the 3’
end. The responsible enzyme is called RNA polymerase.
1. The genetic material determines what organisms look like (13/38)

Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’
1. The genetic material determines what organisms look like (14/38)

Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’
1. What direction is the pre-mRNA going to grow toward? ← or →?
1. The genetic material determines what organisms look like (14/38)

Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’
1. What direction is the pre-mRNA going to grow toward? ← or →?
2. Transcribe the DNA strand and show the resulting RNA strand.
1. The genetic material determines what organisms look like (14/38)

Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ pre-mRNA 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’
1. What direction is the pre-mRNA going to grow toward? ← or →? 2. Transcribe the DNA strand and show the resulting RNA strand.
1. The genetic material determines what organisms look like (14/38)

Translation: RNA to proteins
1. The genetic material determines what organisms look like (15/38)

Translation: RNA to proteins
􏰁 Ribosomes translate mRNA molecules into proteins outside the nucleus with the help of tRNAs (transfer RNAs).
1. The genetic material determines what organisms look like (15/38)

Translation: RNA to proteins
1. The genetic material determines what organisms look like (17/38)

Translation: RNA to proteins
􏰁 A codon is a group of three consecutive nucleotides.
1. The genetic material determines what organisms look like (17/38)

Translation: RNA to proteins
􏰁 A codon is a group of three consecutive nucleotides.
􏰁 Codons have complementary tRNAs that bring an amino acid to
be added to the growing protein.
1. The genetic material determines what organisms look like (17/38)

Translation: RNA to proteins
􏰁 The first codon in a coding sequence is the start codon (the first AUG), the last is the stop codon (UAA, UAG or UGA).
1. The genetic material determines what organisms look like (18/38)

Translation: RNA to proteins
􏰁 The first codon in a coding sequence is the start codon (the first AUG), the last is the stop codon (UAA, UAG or UGA).
􏰁 An open reading frame (ORF) is a “translatable” continuous segment of a mature mRNA between a start codon and a stop codon.
1. The genetic material determines what organisms look like (18/38)

Translation: RNA to proteins
1. The genetic material determines what organisms look like (19/38)

Translation: RNA to proteins
􏰁 A sequence of codons is “translated” into a sequence of amino acids according to a genetic code.
1. The genetic material determines what organisms look like (19/38)

Translation: RNA to proteins
􏰁 A sequence of codons is “translated” into a sequence of amino acids according to a genetic code.
AUC Ile AUA
GGU U GGC Gly C
G GUC GUA GUG
GCC GCA GCG
1. The genetic material determines what organisms look like

Translation: RNA to proteins
􏰁 There are 64 possible codons to code for only 20 amino acids. The genetic code is thus redundant, or degenerate.
AUC Ile AUA
GGU U GGC Gly C
G GUC GUA GUG
GCC GCA GCG
1. The genetic material determines what organisms look like

Quiz (continued)
Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ pre-mRNA 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’
1. The genetic material determines what organisms look like (20/38)

Quiz (continued)
Template strand 5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ pre-mRNA 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’
1. Translate the pre-mRNA sequence. UCAG
UUU Phe UCU U UUC UCC UUA Leu UCA UUG UCG CUU CCU C CUC Leu CCC CUA CCA CUG CCG AUU ACU A AUC Ile ACC AUA ACA AUG Met ACG GUU GCU G GUC Val GCC GUA GCA GUG GCG
UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG
His Gln Asp Glu
UGU Cys U UGC C UGA Stop A UGG Trp G CGU U CGC Arg C CGA A CGG G AGU Ser U AGC C AGA Arg A
1. The genetic material determines what organisms look like

Quiz (continued)
Template strand pre-mRNA mRNA
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’ 3’ AAAGAUUAGGUUUCUGUAUUU 5’
1. Translate the pre-mRNA sequence. UCAG
UUU Phe UCU U UUC UCC UUA Leu UCA UUG UCG CUU CCU C CUC Leu CCC CUA CCA CUG CCG AUU ACU A AUC Ile ACC AUA ACA AUG Met ACG GUU GCU G GUC Val GCC GUA GCA GUG GCG
UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG
His Gln Asp Glu
UGU Cys U UGC C UGA Stop A UGG Trp G CGU U CGC Arg C CGA A CGG G AGU Ser U AGC C AGA Arg A
1. The genetic material determines what organisms look like

Quiz (continued)
Template strand pre-mRNA mRNA (flipped) mRNA
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’ 3’ AAAGAUUAGGUUUCUGUAUUU 5’
5’ UUUAUGUCUUUGGAUUAGAAA 3’
1. Translate the pre-mRNA sequence. UCAG
UUU Phe UCU U UUC UCC UUA Leu UCA UUG UCG CUU CCU C CUC Leu CCC CUA CCA CUG CCG AUU ACU A AUC Ile ACC AUA ACA AUG Met ACG GUU GCU G GUC Val GCC GUA GCA GUG GCG
UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG
His Gln Asp Glu
UGU Cys U UGC C UGA Stop A UGG Trp G CGU U CGC Arg C CGA A CGG G AGU Ser U AGC C AGA Arg A
1. The genetic material determines what organisms look like

Quiz (continued)
Template strand pre-mRNA mRNA (flipped) mRNA Protein
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’ 3’ AAAGAUUAGGUUUCUGUAUUU 5’
5’ UUUAUGUCUUUGGAUUAGAAA 3’
Met – Ser – Leu – Asp – Stop
1. Translate the pre-mRNA sequence. UCAG
UUU Phe UCU U UUC UCC UUA Leu UCA UUG UCG CUU CCU C CUC Leu CCC CUA CCA CUG CCG AUU ACU A AUC Ile ACC AUA ACA AUG Met ACG GUU GCU G GUC Val GCC GUA GCA GUG GCG
UAU UAC UAA UAG CAU CAC CAA CAG AAU AAC AAA AAG GAU GAC GAA GAG
His Gln Asp Glu
UGU Cys U UGC C UGA Stop A UGG Trp G CGU U CGC Arg C CGA A CGG G AGU Ser U AGC C AGA Arg A
1. The genetic material determines what organisms look like

Quiz (continued)
Template strand pre-mRNA mRNA (flipped) mRNA Protein
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGAUUAGCGAAGGUGAUCCGUUUCUGUAUUU 5’ 3’ AAAGAUUAGGUUUCUGUAUUU 5’
5’ UUUAUGUCUUUGGAUUAGAAA 3’
Met – Ser – Leu – Asp – Stop
1. Translate the pre-mRNA sequence.
2. There is only one ORF in this sequence, but in any real example, you would have to scan the sequence six times to potentially find the ORF. Why?
1. The genetic material determines what organisms look like (20/38)

Quiz (continued)
3. Who do we share our genetic code the most with: chimpanzees or fruit flies?
1. The genetic material determines what organisms look like (21/38)

In summary, this is the central dogma
1. The genetic material determines what organisms look like (22/38)

Movie recommendation
’ Moon (2009), Sony Pictures Classics
1. The genetic material determines what organisms look like (24/38)

A DNA molecule can change over time due to mutations
􏰁 The simplest type of mutation is called a point mutation and it affects a single nucleotide.
Original template str. Original coding str. Original mRNA Original protein
Mutated template str. Mutated coding str. Mutated mRNA Mutated protein
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCTGTATTT 5’ 5’ UUUAUGUCUUUGGAUUAGAAA 3’
Met – Ser – Leu – Asp – Stop
5’ TTTCTAATCGCTTCCACTAGGCAAAGCCATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCGGTATTT 5’ 5’ UUUAUGGCUUUGGAUUAGAAA 3’
Met – Ala – Leu – Asp – Stop
1. The genetic material determines what organisms look like (26/38)

A DNA molecule can change over time due to mutations
􏰁 The simplest type of mutation is called a point mutation and it affects a single nucleotide.
Original template str. Original coding str. Original mRNA Original protein
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCTGTATTT 5’ 5’ UUUAUGUCUUUGGAUUAGAAA 3’
Met – Ser – Leu – Asp – Stop
5’ TTTCTAATCGCTTCCACTAGGCAAAGCCATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCGGTATTT 5’ 5’ UUUAUGGCUUUGGAUUAGAAA 3’
Met – Ala – Leu – Asp – Stop
􏰁 The mutation above does change the coded amino acid: it is a
Mutated template str. Mutated coding str. Mutated mRNA Mutated protein
nonsynonymous (or missense) mutation.
1. The genetic material determines what organisms look like (26/38)

A DNA molecule can change over time due to mutations
􏰁 The simplest type of mutation is called a point mutation and it affects a single nucleotide.
Original template str. Original coding str. Original mRNA Original protein
5’ TTTCTAATCGCTTCCACTAGGCAAAGACATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCTGTATTT 5’ 5’ UUUAUGUCUUUGGAUUAGAAA 3’
Met – Ser – Leu – Asp – Stop
5’ TTTCTAATCGCTTCCACTAGGCAAAGCCATAAA 3’ 3’ AAAGATTAGCGAAGGTGATCCGTTTCGGTATTT 5’ 5’ UUUAUGGCUUUGGAUUAGAAA 3’
Met – Ala – Leu – Asp – Stop
􏰁 The mutation above changes a purine “A”

程序代写 CS代考加微信: powcoder QQ: 1823890830 Email: powcoder@163.com

Related Posts