Genetics, Epigenetics and Comparative Genomics

Question 1

Types of mutation

Answer 1

mutations and non-homologous recombination create diversity
gene duplication
- duplication of opsin genes on X occurred independently in different species
- duplicated genes diverged to produce photopigments for colour vision
point mutations = change in single base
- silent = different codon encodes same AA
- nonsense = new codon encodes stop
- missense = new codon encodes a different AA
frameshift mutations = insertion or deletion
- alters all codons after the mutation

Question 2

Transposons

Answer 2

• jumping genes
• most of human genome is made up of repetitive elements
• most of these are transposons or transposon-like elements
• some have lost their ability to jump
• repetitive elements associated with more replication errors

Question 3

Simple traits

Answer 3

• affected by a single SNP
• e.g. earwax wet or dry encoded by a single SNP
• not currently adaptive so likely genetic drift

Question 4

Intermediate traits

Answer 4

polygenic but have genes of major effectcom

Question 5

Complex traits

Answer 5

• influenced by many genes and environmental factors
• twin studies separate the influence of genetics and environment

Question 6

Heritability

Answer 6

percentage of phenotypic variation on a population level which can be attributed to genetic variation over environmental variation

Question 7

GWAS

Answer 7

• looks for SNPs
• increased sample size required to reach higher levels of heritability but still won’t reach that of twin studies!
• this is known as missing heritability, and is caused by epistasis, rare variants and pleiotropy
• issues with GWAS = European bias, population structure and genetic architecture

Question 8

Genetic drift

Answer 8

• genetic bottlenecks = decrease in original population
• genetic drift occurs as survivors mate
• causes allele frequencies in isolated populations to diverge over time
• frequencies of alleles change independently
• more quickly in small populations
• drift can drive evolution but only selection drives adaptive evolution

Question 9

Migration

Answer 9

• quicker than mutation
• recovers variation
• migration carries a subset of the genetic diversity from source population
• some alleles lost during migration

Question 10

Assortative mating

Answer 10

• occurs when individuals with similar phenotypes are more likely to mate
• effectively decreases population size
• increased effect of genetic drift and reduced diversity
• disassortative mating has opposite effect

Question 11

Selection

Answer 11

• acts on diversity via reproductive fitness
• natural selection requires heritable variation in the population and differential reproductive success
• selection may be against alleles of introgression which may be deleterious for male fertility
• selection drives adaptive evolution

Question 12

Reproductive fitness

Answer 12

• surviving long enough to mate
• ability to attract a mate
• fertility
• number of offspring

Question 13

Selection versus drift

Answer 13

• effective population size: smaller population = more drift
• relative fitness of the phenotype
• the type of selection
• the frequency of the allele under selection

Question 14

Neutral theory

Answer 14

• most mutations are subject to drift rather than selection
• main type of selection is negative, against deleterious mutations
• positive and balancing selection are rare
• most polymorphisms will be fixed or eliminated by drift and have little or no effect on fitness

Question 15

Signals of selection

Answer 15

• hard sweeps = one allele increases in frequency to fixation e.g. malaria resistance and lactase persistence (monogenic)
• can identify hard sweeps as selection decreases diversity as other alleles decrease in frequency
• soft sweep = many alleles from same locus increase in frequency so never get to fixation
• soft sweeps also occur on standing variation when alleles were previously neutral or slightly deleterious

Question 16

Human diversity

Answer 16

• low genetic diversity compared to chimps
• reduced heterozygosity from Africa outwards
• could reflect low ancient population size
• migration only carries a subset of genetic diversity

Question 17

Adaptation to high altitude

Answer 17

• low migration allows highly localised adaptation
• hypoxia selection pressure at high altitude
• Andean, Ethiopian and Tibetan populations
• 3 populations have very different physiological responses to high altitude, for example in HNF1alpha (TF) and EPO
• convergent adaptation of EPO response between populations
• Tibetan population reflects admixture between populations

Question 18

Agriculture

Answer 18

• agriculture developed independently
• spread via migration or trade and exchange?
• cultural diffusion = culture spreads and enables growth (South Asia)
• demic diffusion = culture and genes spread together (Europe)
• domestication of animals = more disease = farmers have some tolerance, HGs don’t

Question 19

Lactase persistence

Answer 19

• mutations producing lactase persistence in Europe are in a non-coding regulatory region upstream of lactase gene
• gene-culture co-evolution
• range of other mutations = convergent evolution
• drinking milk postdates farming so how was it under selection?
• maybe difference in fitness comes about in times of starvation when need to drink lots of milk

Question 20

Malaria resistance

Answer 20

• Duffy -ve allele confers resistance to Plasmodium as cannot enter RBCs
• adaptations have costs for immune function so only selective for parts of world where malaria is common
• GWAS shows selection for Duffy -ve in Malagasy populations
• and analysis suggests drift alone couldn’t be responsible for these levels so must be positive selection
• carried other genes with it
• areas with higher malaria infection have higher sickle cell trait

Question 21

Endogamy

Answer 21

• reduced diversity
• increased homozygosity
• recessive alleles more likely to impact phenotype

Question 22

Consanguinity

Answer 22

• marrying cousins
• strong link with disability e.g. Pakistani populations
• Tunisia = prenuptial counselling for blood relatives is mandatory

Question 23

Epigenetic modifications

Answer 23

• methylation = allows TF binding = increased expression
• histone methylations = prevents TF binding
• histone acetylation = allows TF binding
• non-coding RNAs regulate genes at the post-transcriptional level

Question 24

Genomic imprinting

Answer 24

• some genes are imprinted depending on whether from mother or father
• imprinting changes how much gene is expressed
• genomic imprinting co-evolved with viviparity (live births) which increases resource burden on mother
• mainly maternal expression = big brain, small body and placenta (schizophrenia?)
• mainly paternal expression = small brain, large body and placenta (autism?)
• conflict between mother and fetus = hypertension, preeclampsia, gestational diabetes etc.

Question 25

Paternal obesity

Answer 25

- paternal obesity = reduced methylation of some imprinted genes in sperm - can influence metabolism and fat storage = obesity in child

Question 26

Stress and epigenetics

Answer 26

- early life stress risk factor for e.g. anxiety, depression etc - more attentive rat mothers have less anxious pups