BIS126 Genetics and evolution

what was jean Baptiste de Lemark’s theory of inheritance

Inheritance of acquired characteristics 

organs that are used most evolve within the organism and offspring develop these characteristics 

e.g. giraffes stretching their necks 

what was Darwins theory of inheritance

he didn’t know how inheritance worked

noticed preservation of favourable characteristics and called it natural selection

how was the modern synthesis of evolution (1940) created

darwinian ideas of selection was combined with mendels work on genetics

what are the 3 ingredients of evolution

variation → inheritance→ selection

examples of some ways to study evolution 

1. field- based studies (e.g Darwins finches)

2. experimental evolution (e.g e.coli populations)

3. comparative approaches (e.g primate genome project)

examples of adapting to new environments

• peppered moths "bison betularia”

• tibetans and high altitude

• covid-19 strains

examples of evolution of resistance

• warren resistance in rats

• antibiotic resistance/ MRSA

examples of domestication

• dogs - much inbreeding so high frequency of genetic diseases that can be studied

• plants - brassicas

what does evolutionary change require

variation that is heritable and affects fitness

What are the two types of nucleotide base structures?

Pyrimidines and purines

What is a purine?

2 rings (adenine and guanine)

what is a pyrimidine?

one ring (cytosine, thymine, uracil)

Watson and crick’s DNA structure

• A-T and C-G H-bonded base pairs

• antiparallel strands (opposite 5’ to 3’ directions)

• right handed double helix

• one turn every 10.5 bp

• DNA strands complementary

• 3 H bonds G-C, 2H bonds A-T

RNA and DNA main differences

• Nucleotide contains ribbons instead of deoxyribose in pentose (missing oxygen)

  RNA contains uracil instead of thymine

• RNA is often one stranded

Where is DNA found in prokaryotes?

No internal structure such as nucleus

DNA is condensed in a structure called the nucleiod

single stranded DNA molecule densely packed with genes

few million bases

also contain smaller plasmids (thousands of nucleotides) passed from cell-cell in certain circumstances

Where is DNA Found a eukaryotes?

Contained the nucleus, eukaryotic chromosomes are linear

Structure of chromosomes in eukaryotes

p arm, q arm, telomeres, centromere

P arm

Shorter chromosome arm

q arm

Longer chromosome arm

Telomere

structures at the end of linear chromosomes that protects from degradation

Centromere

Specialised region, that acts as a binding site for the binding of kinetochore proteins important for mitosis meiosis

What are eukaryotic chromosomes made of?

Chromatin= DNA + histones

What is the central dogma?

DNA makes RNA makes protein

transcription + translation

amino acid

What's the difference between different R groups?

Shapes and sizes, electric charge ,polarity

Gene definition

Unit of hereditary information occupies a fixed position (locus) on a chromosome

Gene expression definition

The process of transferring the information in a gene to a functional protein needs to be controlled. Gene is not expressed equally.

Initiation sequence at the promoter

Conserved sequences just before the transcription starts, recognised and bounded by RNA polymerase subunits

termination sequence

At the end of the gene, sequence that makes polymers slow down and therefore dissociate from DNA

Operon

A group of genes with a single promoter in bacterial gene

genes are often needed in similar circumstances to expression is controlled together

When do transcription translation occur in prokaryotes?

Simultaneously, several ribosomes can work to translate the RNA molecule at the same time process begins before transcription is finished therefore large amounts of protein can be built up quickly

What are the type of sections of mRNA?

Exon's, intron and UTRs

What are Exon?

Protein coding sequences

What are introns?

Regulatory sequences needed to be removed in a process called splicing before mRNA is ready to be translated

What are UTR's?

untranslated regions that direct the ribosomes

What is added to the ends of mRNA?

5’ and 3’ PolyAtail added to mRNA, which is an export from the nucleus to the cytoplasm

What role does complementarity provide?

Provide a mechanism to replicate DNA

What sort of replication of DNA occurs?

Semiconservative, the complementary standards are separated and each is used as a template for new DNA strands which was predicted by Watson and Crick in the original DNA model

What is the origin of replication?

specific DNA sequences where cellular machinery begins duplicating a genome, acting as binding sites for initiator proteins that unwind the DNA, creating replication forks for bidirectional synthesis

Two replication forks proceed from each one

How many origins of replication in prokaryotes versus eukaryotes?

One in prokaryotes and thousands in eukaryotes

What are the two strands in replication?

Leading and lagging strand

Which is the leading strand?

In direction from five prime to 3 prime

DNA synthesis points towards the replication fork and can proceed continuously

follows Helicase

Which is the lagging strand?

Five prime to 3 prime

Points away from the replication and must therefore be a discontinuous

Primed numerous times

What is the mechanism of DNA polymerase?

Adds nucleotides one at a time in a five prime three prime direction

primer starts it

can only add to three prime end

uses template strand to form hydrogen bonds tells which base to add next

rate of 10/100s of nucleotides per second can only add nucleotides an existing strand

What does primase do?

Generate a primer, ligase joins the stretches of new DNA

What does a short RNA primer indicate?

Start point for replication

What does topoisomerase do

Release pressure from overwinding around the replication by making and resealing breaks the DNA

What does SSB do?

Single strand binding protein binds to the separated transparent them from renaneling

What are Okazaki fragments?

The piece of DNA that are stuck together to make up the lagging strand

is ploidy level conserved in mitosis

yes

role of spindle

separate sister chromatids to different daughter cells, microtubules get shorter pulling chromosomes to the poles

centromeres

specialised chromosome regions that direct the equal segregation of chromosomes

connected to microtubules via a large protein complex called the kinetochore

binary fission

binary fission begins with replication of DNA

FtsZ is distributed throughout cell

the cell elongates

FtsZ moves to middle of cell

chromosomes move to opposite ends of cell

FtsZ gathers at midpoint between them

FtsZ directs the formation of the septum made of plasma membrane and cell wall materials

the cell pinches in half and 2 daughter cells formed

What is the nuclear cycle in typical animal?

Diplo most of life cycle

two mating cycles

germline cells that separate from the rest of the animal

then meiosis occurs giving four haploid gametes these combined to give a zygote with all the genetic info needed

What is the nuclear cycle in budding yeast?

Haploid through most of the life cycle

Two types a and alpha determined by a single locus

One a and one alpha combined to give a transient diploid stage

Then meiosis occurs

Giving four haploid products which then developed into the normal building form

Nomenclature for replicated chromosomes

Diploid organisms have two homologous chromosomes same genes but could have different versions of them

each chromosome is replicated to give two identical Sister chromatids

the Sister chromatids are joined together with a single centromere structured called a dyad

meiosis I: first division stages

1. interphase- homologous chromosomes

2. prophase I - each replicated chromosome = dyad, 2 sister chromosomes with a single centromere

3. metaphase I - bivalent = 2 dyads joined together

4. anaphase I - dyads moved to different poles, centromeres stay intact

5. telophase I

By and have two nuclear both containing both Sister) chromatids of one chromosome from each pair of homologous pair different from each parent cell

Stages of crossing over

Holds non-Sister chromatids together

1. Leptotene - replicated chromosomes start to contract

2. Zygotene- chromosomes line up in homologous pairs = synapsis held together by protein called the synaptonemal complex relies on recognition of similar sequences

3. Pachytene - crossing over/ genetic exchange between non sister chromatids

4. diplotene - chromosome separate a bit but sites of crossing over is still visible

5. diakinesis - chromosomes contract further

meiosis ii stages

Sister chromatids lineup together

centromere splits

chromatids moved to opposite poles

by the end four nuclei 2 contain one copy of first homologous chromosome of the pair other 2 contains one copy of the second

What is recombination?

The process by which new combinations of alleles are generated during meiosis through independent assortment and crossing over

What are crossovers?

Sites of genetic exchange between homologous sequences on nonsense credits

How do crossovers occur?

Double strand breaks are made deliberately by specialist enzymes

homologous recombination occurs; relies on chromatids aligning identical sequences sections of the chromosome are swapped giving new allele combinations

What is linkage?

If genes are closer together, it is less likely there will be crossover between them and more likely they will be inherited together

How many possible combinations of chromosomes for humans?

For 23 human chromosomes 2²² = 4194304 combinations

Benefits of recombination

Can produce new fitter gene types can also break up co adaptive gene combinations and speeds up evolution in sexual organisms

Mutation definition

The process that produces a gene of chromosomes that differ from that of the wild type

The gene or chromosome sets the results from such a process

Wild type definition

The form that predominates in nature or in a standard laboratory stock

What is a point mutation?

Small scale mutations, one or a few nucleotides

What types of mistakes can happen during replication?

Incorrect base added, replication slippage

How is an incorrect base added during replication?

DNA polymers adds the wrong nucleotide despite proofreading activity if undetected passed on to all daughters

How does replication slippage occur during replication?

Dissociation of the DNA polymerase during replication, new DNA strand might re-hybridrise in the wrong place, replication continues yielding adult strand that is longer shorter than the template, very common for micro satellites

What is a micro satellite?

Short repeated sequences e.g CAG

Are Satellite DNA copy numbers the same between individuals

No different number of repeats between individuals, different alleles on each chromosome, most of the time phenotypically neutral, some exceptions e.g. too many copies of CAG causes Huntington's disease

How can point mutations caused by environmental mutagens?

For example, UV light can link together adjacent bases, bulky structure blocks DNA polymerase during replication and therefore causes breaks DNA which are not always prepared correctly

How are complete mutations caused by the cellular environment

For example, reactive oxygen species are generated by various cellular processes and damage DNA bases,

For example, guanine is oxidised to 8-oxoG which pairs with A instead of C causing a single nucleotide change

How are mutations potentially reversed? e.g mismatch repair.

Recognises removes and resynthesises mismatched DNA due to mistakes in replication

Various methods depending on species to differentiate the template from the new incorrect strand

This is in addition to proofreading activities of DNA polymerase

Types of point mutation

Silent - no change to amino acid sequence

Nonsense-introduction of a stop codon in a gene

Missense - changes to an amino acid sequence varying effect on protein function

Null allele - total loss of function

Where do mutations have the most profound effect?

In the control region of genes, promoters, splice sites, et cetera

Example of phenotypic polymorphisms due to point mutations

Sickle cell anaemia caused by a single amino acid change in beta globin

Why are mutations in non-coding regions useful?

Mutations more like to be neutral and greater conservation of protein coding compared to intergenic regions

Variation in single nucleotide polymorphisms SNP's can be useful to scientist when carrying out mapping

How can transposons disrupt genes?

A.k.a. jumping genes or mobile genetic elements move around the genome using a copy and paste and cut and paste mechanism

They insert themselves at new genomic locations often random, including inside genes which can disrupt their functions

Can also carry genes or part of genes around with them leading to genes being duplicated or shuffled around

How are genes transferred in prokaryotes?

Horizontally

transformation: pieces of genomic DNA taken up an integrated into the bacterial chromosome

Conjunction: close contact between Donor and recipient cell, plasma or genomic DNA transferred via specialised structure

Transduction: DNA injected by viruses along with the viral genome

examples of large scale mutations

aneuploidy, polyploidy, chromosomal rearrangements

what is aneuploidy

one or a few chromosomes missing e.g. 2n+1, n-2

generated by faulty meiotic division: 2 chromosomes/chromatids go to pole, none to the other

embryos with imbalanced chromosome number generally not viable (down syndrome counter example)

what is polyploidy

unusual number of chromosome sets, comes from unusual meiotic events

even number of chromosomes often fine, triploids etc unable to pair chromosomes properly

triploidy

3n

tetraploidy

4n - common in plants and usually bigger

monoploidy

1n (when 2n common)

what causes chromosome rearragment

incorrect repair of double strand breaks

consequences of chromosomal rearrangemts

whole chromosome - embryos generally not viable

inversions/ translocations - might separate genes from important control regions etc, will cause problems during meiosis: homologous sequences line up together

types of chromosomal rearrangements

deletions - part of the chromosome is missing

inversions - part of the chromosome has been flipped

translocation- part of chromosome has been moved

effects of spontaneous mutation

generates new alleles of a gene, can be harmful, beneficial or neutral to the cell

dominant or recessive depending on the nature of the change of the protein

benefits of redundancy and pseudogenes

through various means genes can be duplicated

this allows extra freedom for evolution: one copy free for experimentation

less selective pressure

possible fates of a duplicated gene

• accumulation of mutations → pseudogene

• one copy gains a new function

• each copy specialises (protein has 2 different functions or adapt to different circumstances)

pseudogene

gene that has lost ability to code for a functional protein

example of gene duplications

globin family - carry O2

why is the garden pea studied for genetics (Pisum Sativum)

• comes in a wide variety of phenotypes; single gene

• readily available, short generation time, large no. of progeny

• usually breeds by self pollinations (true breeding) easy to manipulate/cross

how does cross pollination in peas occur

• anther removed before they shed pollen

• transfer pollen between plants

what was mendels first cross

purple x white

all progeny F1 were purple, same with reciprocal cross

what was mendels 2nd cross

purple F1 x purple F1

F2 ratio of 3:1 even with different characterisics

what did Mendel reason after his crosses

• alternative versions of one cause variation - alleles

• an organism inherits 2 alleles, one from each parent

• alleys may be dominant or recessive (explains F1 gen)

• alleles segregate during gamete production