BIOLOGY RESEARCH TASK

MUTATION TYPES
type process effects Example
Point One base pair If in intron – not too much Sickle cell
inserted/deleted/substituted impact – probably ends up as anaemia
silent/neutral Missense
Happens in DNA replication- If in exon- can be silent (new substitution
mitosis/meiosis (cell division) codon codes for same in gene
amac)/neutral (different amac coding for
but same type, same haemoglobin
function)/missense/nonsense, makes the
which effect phenotype molecules
stick
together
Frameshift Happens when one base pair Always will be a missense – Cystic
inserted/deleted so whole entire polyp affected fibrosis –
sequence shifts two
insertions
and one
deletion in
exon 7 in
CFTR gene
Chromosomal Deletion/insertion/duplication Will always have a large impact Cri du chat-
of gene in chromosome- on phenotype because more Partial
happens in crossing over entire chromosome is affected deletion on
not just one gene/one base pair chromosome
Translocation and inversion – of the gene. 5
crossing over (translocation
when wrong genes swapped
on chromosomes)

Aneuploidy – happens when

nondisjunction in anaphase
and cytokinesis (segregation
of chromosomes as cell
divides) so wrong no. of
chromosomes in daughter
cells

All can be inherited if in germline cells (e.g., sickle cell anaemia) – increase variation in germline by
introducing new allele

Not inheritable if in somatic (breast cancer caused by BRCA1 OR BRCA2 SNP in chromosomes 17 and
13)

Can also happen from mutagens – CAN GENERATE NEW ALLELES BENEFICIAL IN ADAPTATION
Mutations in introns:

Usually = SNP (like BRCA1 and 2)

Enhance/suppress exons

Nuclear RNA (decides which parts of pre mRNA spliced)

rRNA – affects ribosome ability to make polypeptides

mutations in exons:

mismatch repair enzymes (polymerase 1) = can’t fix errors made in replication  mutation

spliceosome genes = spliceosomes can’t splice properly

tumour suppressor genes = can’t suppress tumours (BRCA 1 AND 2

proto-oncogenes = (regulate cell growth and division) cells divide uncontrollably = invasive

SAY IMPACT ON PHENOTYPE THROUGH POLYP (EXPLAIN WHOLE CHAIN REACTION BC OF

MUTATION)

Transposons can jump from one locus to another. This means they increase the chance of
chromosomal translocation mutation. If this occurs in the germline cell and creates a new
allele (by altering polypeptide and thus phenotype) it can be inherited and becomes part
of the genome. If it has good or no impact on individual survival, it continues on in the
genome and can increase in frequency. If is lethal or has harmful impact on individual
survival, individual will die and allele will not become part of genome. If does = gene
variation increased as new allele introduced.
e.g.,
EXAMPLES:
Intron – as above
Exon – as above – breast cancer (BRCA1 AND 2 mutations = tumour-suppressor genes
Germline – sickle cell disease (same as point but say in germline)
Somatic - lung cancer (TP53 – protein code, EGFR, KRAS chromosomal deletions losing
mentioned genes) – BRCA 1 AND 2 ARE IN GERMLINE

ALLELE FREQUENCY
HARDY-WEINBERG PRINCIPLE

Assume that natural selection, mutation, etc. do not exist

Find ratios of population alleles

For heterozygous cross:

AA : 2Aa : aa

= p2 + 2pq + q2

=1

P = A, q = a

Use this for estimations in gene drift, gene flow (bottleneck and founder effect respectively)

Find p = dom/all

Q = rec/all

p2 = 1 – (2pq + q2)

q2 = 1 – (p2 + 2pq)

USES OF GENE SEQUENCING

To sequence a whole gene so entire sequence of a gene is known – know what protein it codes for,
know how protein can change if sequence changed (affect of mutations) – how it is associated with
certain non-infectious disease

(PCR  PCR with ddNTPs  capillary electrophoresis = electropherogram  computer =

chromatogram)

IN POPULATION/CONSERVATION GENETICS
Introns of MtDNA or chDNA sequenced to find number of haplotypes in a population – e.g., mtDNA
of koalas sequenced (because it’s all from mother so provides a direct lineage – makes the research
more efficient, less errors, and more certain of the haplotypes, because know that they are all from
one lineage) –

There is one allele for mtDNA (because it’s only from mother) so only that allele can be inherited (if
don’t consider mutations that may give rise to new alleles)– hence, if any individual has a different
base pair in their mtDNA, that is a mutation in the intron (or an SNP if it occurs in more than 1% of
the species population) and any individual with the specific mtDNA sequence that has that exact
changed base pair is in the same haplotype. (haploid genotype)

The more haplotypes there are, the more genetically diverse a population is. If any individuals have
the same haplotype, they are closely related (may be siblings, cousins, grandchildren, etc.) – usually
means they are part of one family tree in the population.

*changes in mtDNA and chDNA make them SNPs

Can also use SNPs, but since there are two alleles for SNPs, must use one parents’ for all of
population- father or mother? any differences in SNPs produce a haplotype, individuals with the
same differences are in the same haplotype.

All of this needs sequencing

The aim of this is to find out how genetically diverse a population is – if its diversity is too low, that
may mean it is endangered and scientists may step in to help the species survive- if diversity is low, it
means that inbreeding is more likely and, with inbreeding, the frequency of inherited disease rises.

IN DISEASE
Pathologists use DNA sequencing in a cancer patient to identify the type of cancer they have (seeing
the mutated base(s) of the gene).

Used in screening for disease in newborns for early detection and treatment and for medical
research on disease association with certain genes. – blood sample from newborn contains DNA –
DNA is sequenced – look for mutations in DNA that are related to some disease – hence diagnose the
disease, if any.

Usually, SNPs tested because they can be uniquely linked to a particular disease. If this SNP is found
in the sequence, the offspring is prone to or has the disease. (would have to sequence SNP first to
identify it as linked with the particular disease)

Must control for ancestry because people of same ancestry can have similar SNPs that aren’t linked
to a disease. If don’t = population stratification.

Human gene mutation database (HGMD)- info on germline mutations and inherited disease

Catalogue of somatic mutations in cancer (COSMIC)- info on somatic and mitochondrial mutation and
cancer

Human mitochondrial genome (MITOMAP)- info on somatic and mitochondrial mutation

Example- cancer – bcra1 and 2

BRCA1 AND BRCA2 (tumour suppressor genes in chromosome 17 and 13 respectively- code for
proteins that regulate cell division  mutation means cell divides uncontrollably) gene mutations
put women at risk of breast cancer (affects 1/600) – increases risk by 85%. Those that carry either
mutated gene have increased risk with increased age.

Sequencing BRCA1 AND BRCA2 can help screen for the cancer or predict it.

IN ANTHROPOLOGY
mtDNA is sequenced to provide prove for Eve Hypothesis- how?

mtDNA usually has mutation rate of one nucleotide per 3500 years

sequencing mtDNA introns shows a map for evolutionary changes by seeing the mutations that have
occurred in the mtDNA- the more mutations, the longer it has taken for them to develop.

If two tested individuals have the same mtDNA introns but have one nucleotide different, it means
their last common ancestor was 3500 years ago, according to the mutation rate.
So sequencing mtDNA allows to see how closely related human populations are –

Out of africa theory-

Archaic homo sapiens left Africa first 2mya and spread to different countries without gene flow
between them. a second migration out of Africa happened 100 000 ya and these were modern
humans which out-competed and replaced the homo sapiens of the last migration in the other
countries – again no gene flow between countries.

mtDNA sequencing is evidence for this theory – individuals with the same mutations were
descendents of the same common ancestor (= same haplogroup). Most genetic variation is found in
africa with this sequencing – makes sense since they are the oldest group of humans so their mtDNA
would have had more mutations than any other ethnicity so more variation there.

multiregional theory states homo erectus left Africa 2mya, went to different countries and there was
gene flow between them. for this to be true, genetic variation would be high everywhere in the
world and a person in one country would contain ancient alleles of ancestors from other countries –
BUT people of a country tend to have the same ancient alleles of ancestors from the same country as
them – hence – unlikely theory.

Interbreeding with Denisovans in Australia and Altai mountains. Interbreeding with Neanderthals in
Eurasia, America, Altai Mountains –

Know this because mtDNA analysis showed some archaic DNA in these ethnicities from the two
subspecies of humans

mtDNA has less DNA so more efficient and all from mother os direct lineage so more efficient

introns have mutation rate – use this to know how similar or diverged two populations/species are

exons code for respiration – use to see how similar species are

USES OF GENE PROFILING

IN POPULATION/CONSERVATION GENETICS
The idea here is that it allows us to verify behaviours of species for example at a population level.
Further to this, we can get quick comparisons between families or distinct populations as an
indicator of genetic diversity by finding how many different STRs are present. This is done in koalas to
establish differences in haplotypes and therefore genetic diversity.

To compare families/distinct populations of a species to indicate how genetically diverse they are by
finding out how many different STRs there are HOW?

In koalas, STRs profiled to make haplotypes (more haplotypes = more diversity) – this can be used to
see if the koalas are endangered (low diversity/few haplotypes)
Though STRs are introns, they can affect phenotype by affecting the exons that surround them
(eSTRs)

GUIRA CUCKOOS

Cuckoo mothers can raise both biological and non-biological chicks in their family. By profiling their
STRs and comparing them to see if they have an allele from the mother, we can see if the chicks are
biologically the mother’s or not. This allows us to confirm this behaviour of the cuckoos.

IN DISEASE
eSTRs have been found to be associated with diseases like bowel disease and schizophrenia. This
means they can be profiled to screen for these diseases

GENE FLOW
A population transfers to another population and transfers alleles with them to the other population
= migration

Increases genetic variation in population with new members as new alleles brought into population
so more allele combinations are possible.

Decreases genetic variation in population whose members emigrated as some alleles had their
frequencies reduced when those members took them to another location. This reduction of
frequency for those alleles decreases gene variation.

GENETC DRIFT
Chance events cause changes in allele frequency of population – larger populations more affected.

Bottleneck effect = natural disaster leaves pops low with changed allele freq and natural selection
follows (if can survive, pop grows again, if can’t pop goes extinct)

Founder effect (when a new population is started by a small number of individuals who are not
representative of the original population and these have reduced variation = portion of a species
emigrates to another geographic location – the new smaller pop in the new area has a different allele
freq than the original species pop and as natural selection occurs, the pop usually grows and evolves
into its own species

Evolution = change in allele freq therefore genetic drift = driver of evolution

Bottleneck effect (when a chance event causes drastic decrease in population size which changes
allele frequencies) – e.g., a bushfire may wipe out majority of brushtail possum in a woodland area
WHY NOT INCREASING GENE VARIATON
Founder effect = small population carrying a fraction of the genetic variation of the original
population as they have different allele frequencies

Bottleneck effect = leaves only a small population with a fraction of gene variation of original
population. The allele frequency has changed and some alleles may have even been lost in the
chance event, which lowers genetic variation.

ROLE OF ISOLATION IN EVOLUTION

Isolation of a population results in the population having different allele frequencies to the original
population before isolation. This can lower genetic variation through the founder effect which is
when a small part of the population moves away from the whole population and becomes isolated.
This lowers genetic variation since allele frequencies are changed in a much smaller population.
Additionally, because the population is isolated, inbreeding becomes more common which further
reduces genetic variation as only certain alleles continue being selected for in future generations.
Afterwards, selection pressures cause those with favourable traits to survive and reproduce to pass
on those traits, while those without favourable traits die out. This causes adaptation as the allele
frequencies change and, if continued longer, causes evolution of the population. However, if the
genetic variation is too low for the organisms to survive the selection pressures, the population can
become extinct.

ADVANTAGES OF REPRODUCTIVE TECH

ARTIFICIAL INSEMINATION (semen  straw  thaw  insert with gun)

ARTIFICIAL POLLINATION (pollen/anther  stigma)

IVF (gamete fusion in vitro  embryo cultured  inserted)

Endangered species-

Endangered species have very low populations. Using artificial insemination/pollination can help
increase their population at a fast rate to help them survive and prevent extinction.

Financial -

Can select for desired characteristics so more crops and more livestock in agriculture are better
quality for the market. Also higher crop yield since more offspring can come from a parent – CAN
HELP WITH WORLD HUNGER

Diversity –

Semen/pollen can be stored and shipped more easily than the organisms themselves. This allows
breeding of more offspring form one parent for a long time in more locations.
Because they can be shipped more easily across borders, the semen/pollen can carry alleles between
distinct populations of a species that are geographically separate and have no gene flow. This allows
the transfer of genes between these populations and hence genetic variation can rise as new allele
combinations can be introduced through interbreeding due to transfer of alleles between the two
populations.

Disease-

For IVF, can screen the embryo for disease for early diagnosis or, if parents wish, to not choose that
embryo as their baby.

Selective breeding can select for alleles that make the organism resistant to disease- so less
pesticides needed and more crops/livestock survive

EXAMPLE-

increase fruit size and seed number for apples so more apple yield – helps in developing countries
where hunger is a problem

EXAMPLE—ANUEPLOIDY CHROMOSOMAL MUTATION

Polyploidy = extra set of chromosomes. This is fatal in humans (e.g., 3N or 4N instead of 2n) BUT it is
a desired trait in plants that produce fruits because it produces large seedless fruits  selected for in
artificial pollination – so better quality fruits (e.g., apples) so helping in developing countries with
famine and farmer income.

DISADVANTAGES OF REPRODUCTIVE TECH

ARTIFICIAL INSEMINATION

ARTIFICIAL POLLINATION

IVF

CLONING- somatic cell nuclear transfer:

egg removed from one organism  somatic cell from organism to be cloned - starved of nutrients so
can’t replicate  egg denucleated  somatic cell inserted into egg by electric current to increase
egg membrane permeability == embryo clone  inserted into a surrogate

Inherited infertility

IVF is often used to help those that can’t reproduce because of infertility. This means that the gene
for infertility has a chance of being passed on to the offspring from IVF. If its use increases in society,
more offspring may inherit this infertility, which would mean that the human population could
become endangered as we would not be able to reproduce at a fast enough rate.

Biodiversity

Because this allows the continued selection of certain desired alleles, genetic diversity can decrease
as allele frequencies of the desired traits rise and dominate the genome to the point where
monocultures are produced. Low gene diversity makes the species susceptible to natural selection
and infectious/non-infectious/inherited disease (by inbreeding)
As some alleles are continuously selected for, their frequency rises – other alleles’ frequencies may
drop so low that they may be lost entirely from the genome – this could lead to unforeseen changes
in the species’ population – e.g., extinction, endangered.

Inbreeding  homozygous individuals rise  vulnerable to disease

EXAMPLE

– e.g., Modern corn is the result of continued artificial pollination on maize in the past. This has
narrowed down allele frequencies so traits like large size dominate the genome, reducing gene
diversity. (the traits have been continuously selected for so not many other combinations of alleles in
genome).

ETHICAL CONSIDERATIONS OF REPRODUCTIVE TECH

IVF – choosing characteristics of offspring

Utilitarian ethics: ethical activity is one that provides greatest balance of good over harm for society
and environment (does it benefit most people?)

Precautionary principle: if there is a doubt about harm that may be caused by an activity, proposers
of the activity must prove the harm is not significant for society or environment (e.g., farmers using
artificial pollination/insemination must prove it doesn’t pose a significant risk for biodiversity)

In whose best interests is the action?

Selective breeding is in the interests of both farmers and consumers- it increases the yield of crops
and the quality of crops (more offspring from one sample for longer and select for desired traits)

This means farmers make more money selling more products with higher quality. Consumers also
consume higher quality products – helps with world hunger, etc.

Environmentally – a trait selected for is often pest resistance – so pesticide use decreased and less
ends up in ecosystem (waterways, soil, etc)

Not in best interest of animals – although it provides good characteristics in offspring (resistance to
disease/pest) it also has side effects = e.g., broiler chicken bred to grow fast and can grow to fast for
its legs. Animal welfare

How reliable/useful is procedure?

Very – one individual’s pollen/semen can be used to produce a lot of offspring from many surrogates
for a long time (since they can be stored for a long time) – this means yield of products can increase
and stay high for a long time.

Instead of shipping livestock/plants across borders (can die/injured on the way) can instead ship the
stored semen/pollen – much more efficient and more samples can be shipped than livestock/crops
(which would take up more room and weight).
The procedure consistently provides good results (good as in lots of offspring with desired traits) –

BUT – is becoming outdated and there are emerging methods – e.g., cloning- which produce more
accurate results faster

Do advantages outweigh risks? (precautionary principle)

Advantages = less disease in products, more income for farmers, higher quality products for
consumers, can ship semen/pollen across countries

Disadvantages = not all farmers can afford it and this perpetuates economic inequality between
farmers (those who have access will continue to sell more, those who don’t sell less). Biodiversity
lowers and species becomes vulnerable to natural selection/disease/competition. Animal welfare
also disregarded. – BROILER CHICKEN

Animal welfare – in artificial insemination, some desired traits are detrimental to animal welfare –
e.g., broiler chicken have allele for fast growth selected for – this causes them to grow too fast for
their legs to support their weight.

Although there are more advantages, the risks have more weight, especially that for biodiversity. So
no- advantages don’t outweigh the risks.

Is there equal access for all members of society? No bias?

No, some farmers can’t afford artificial insemination/pollination methods.

Some people can’t afford IVF treatment.

Also for IVF- concerns about being able to choose the offspring’s characteristics (“designer babies”)

In IVF – choosing the traits of offspring raises concerns about producing ‘designer babies’ which
could arise and rearise political and social issues.

In IVF – embryos that aren’t used for surrogate mother can be used by scientists for research – this is
protested against by some groups, including religious ones, which believe that an embryo is still a
human life and that these procedures are immoral and unnatural.

Concerns about “playing God” in GMOs and transgenesis.

SOCIAL CONSIDERATIONS OF REPRODUCTIVE TECH

Harm to biodiversity and environment/less harm:

From one pov – repro tech reduces biodiversity in the long-term by …

But repro tech can also mean that farmers select for pest-resistant genes in crops – so less pesticides
used and less pesticides end up polluting environment – since agricultural practices are one of the
main factors causing pollution, this would reduce pollution in environment a lot

Also – can select for disease-resistant genes in crops which would mean more crops survive and
higher crop yield means more food and resources for the people – this helps with famine

However – crops that are selectively bred often end up with less nutritional value so consumers
won’t receive enough nutrients they need from the products

Some farmers can’t afford the repro tech (e.g., farmers in developing countries) – they sell less as
they have lower crop yield

Farmers that can afford sell more

So this perpetuates the economic inequality between farmers of different regions

Areas where science is more accepted and which have enough money to afford and sustain the repro
tech are more likely to use it

People want society to progress and develop tech so approve of it but some people also have
religious values against tampering with nature and do not approve of it.

IVF:

Concerns about “designer babies” as parents can choose their offspring’s characteristics

Can contribute to studies about disease since can screen the embryo for disease and investigate
what genes the disease is linked to – helps with early detections and treatment as well.

Religious concerns about the sanctity of reproduction methods

High chance of inherited infertility – if widespread use  more humans with inherited infertility –
risky for continuity of species

Moral and legal status of embryos produced in IVF but not chosen by parents – contribute to
research? But is this ethical?

Society deciding until which stage it’s ok for embryo to be used for research (i.e. at which stage does
it become a legitimate human life?) – many religious groups believe that life of a human begins as
soon as gametes fuse. Others believe that embryos are just living cells and can be used for research
without moral compromise.

Many health risks for mother with IVF: ovarian hyperstimulation syndrome, multiple pregnancies,
higher risk of miscarriage, premature death, ectopic pregnancy

Many health-risks for IVF offspring: learning disabilities, cerebral palsy, chronic lung problems,
mental health problems

Use in agriculture can produce higher quality food (e.g., golden rice has more nutrients) with higher
yield to help with world hunger.
Can select for disease and pest resistance in crops so less pesticide used so less pesticide polluting
environment.

EXAMPLES:

Artificial insemination:

Broiler chicken –

Adv: slow breeders therefore this helps produce more of them so more can be used in agriculture =
revenue + consumer = social

Disadvantages: a desired trait is fast growth so they grow too fast for their legs and can be
injured/die = animal welfare = ethical

Artificial pollination:

Apples-

Adv: more seeds produced so more apples, bigger apples and sweeter – consumer and farmer
benefit = social .

Polyploidy selected for in apples. Polyploidy = more chromosomes than normal in organism =
beneficial for gene diversity because increases no. of possible gene combos.

Disadv example:
Modern corn is the result of continued artificial pollination on maize in the past. This has narrowed
down allele frequencies so traits like large size dominate the genome, reducing gene diversity.
Because of this reduce gene diversity, the corn crops in a farm are prone to disease. If the corn crops
of one farm spread to another and alter the allele frequencies of those corn crops and then a disease
emerges which affects the original farm’s corn, the disease is likely to spread to the farm affected by
the corn. This will cause loss of crop yield for both farms and financial loss for both farms, and only
the original farm will be responsible for both losses. = social

IVF:

Adv- for those who can’t reproduce by other methods- can screen embryo for disease = early
detection/choose not to have that embryo as offspring

Disadv- expensive + concerns about being able to choose characteristics of offspring

TO REVISE (NOT ON SHEETS)

- Process of artificial insemination

- Process artificial pollination
- Process IVF
- Process of DNA sequencing
- Process of DNA profiling