MCQ Flashcards
BROAD-SENSE HERITABILITY
H2 = VG/(VG+VE)
V = variance, G = genotype, E = environment…..
G includes additive genetic variance (allelic differences), dominance effects (vs. recessive), epistasis (G*G interactions) & parental effects
NARROW-SENSE HERITABILITY
h2 = VA/(VA+VE)
VA = additive genetic variance
Problems measuring heritability
- You need intra-specific variation (some traits cannot be measured)!
- It depends on the environmental variation
- Does not explain means but variance
- Female choice and the lek paradox:
constant selection on genes should reduce genetic variation, heritability and evolution →dominant role of nurture!
Introns & Exons
Exons: coding region
Introns:
region that is not translated into protein
transcribed to precursor mRNA and then removed by splicing during processing to mature RNA
Mutations in mitosis
little effect
increase with age
70% harmful
Mutation in meiosis
greater influence as only one cell
- Crossing over/ recombination
essential and facilitated by Spo11 protein which initiates double-stranded breaks
- TRANSCRIPTION
create a complementary RNA copy of a sequence of DNA
- If gene → protein, then RNA is a messenger RNA (mRNA)
- Else ribosomal RNA (rRNA), transfer RNA (tRNA) or ribozymes…
- RNA Polymerase produces complementary, antiparallel RNA strand
- Polymerase binds onto core promoter in the presence of transcription factors → initiation of transcription
- Only some genes are transcribed in each cell
- mRNA SPLICING
remove introns and join exons
- Spicing generally an action of proteins – interestingly, they can do this in various ways (moving exons around, deleting them, sometimes including introns)
- Number of introns per gene increases roughly with complexity, humans have 100s or 1000s / gene
- TRANSLATION
create a chain of amino acids from mRNA
- occurs across the membrane of the endoplasmic reticulum
- ribosome facilitates decoding by inducing the binding of tRNAs with complementary anticodon sequences to that of the mRNA
- amino acids are attached to tRNA and are joined together by the ribosome
- Make millions of different proteins
Waddington 1942 definition of epigenetics
The interaction among genes and between genes and environment that lead to a given development and bring the phenotype alive
Nanney 1958 definition of epigenetics
Mechanisms of inheritance that do not include the DNA sequence
nucleosome
subunit of chromatin composed of a 147 BP length of DNA wrapped around a core of histone proteins
Chromatin
a complex of DNA and protein in eukaryotic cells
changes in chromatin structure affected mainly by methylation and acylation of the nucleosome proteins
4 DIFFERENT WAYS TO INFLUENCE GENE EXPRESSION
- Make the DNA unable to bind RNA transferase (DNA methylation & Gene Switches)
- Make the DNA inaccessible and/or impossible for proteins to bind (Histone Modification & Chromatin Remodelling
- Alternative Splicing the introns and exons to create alternative proteins
- Disrupt translation to influence protein production
DNA METHYLATION
- de novo methyltransferases (enzymes) add methyl groups to CpG sites
- this prevents protiens binding to promoter region in DNA
- gene is silenced
- only occurs in totipotent stage of embryogenesis
DNA METHYLATION: Horizontal Memory
- In mitosis
- maintenance methyltransferase copies over methylation patterns
- →life-long effects of patterns that were established at birth
DNA METHYLATION: Vertical Memory
- paternal genome actively demethylated few hours after fertilization
- maternal genome passively demethylated during early embryogenesis (no maintainance methyltransferase)
- remethylation occurs at implantation
nucleosome
subunit of chromatin composed of a short length of DNA wrapped around a core of histone proteins → allows compaction of DNA by sixfold
Euchromatin
lightly packed form of DNA, regions rich in genes → often under active transcription
Heterochromatin
tightly packed form of DNA, repetitive sequence and regions with few protein coding genes → non-transcribed = silenced
Histone Modification
- post-translation
- tails of histones (H3 and H4)
- modifications such as: methylation (can be repression as well as activation), acetylation & phosphorylation
- can effect: gene expression, DNA repair & chromosome condensation
- horizontal transmission, dont know about vertical
- patterns vary from one organism to the next
3 main functions of histone modification
- alter chromatin structure & weakens or fastens grip on DNA
- inhibit or facilitates binding of transcription factors and other enzymes
- creates binding site for particular protein
possibilities for alternative splicing
- Exon skipping : exon may be spliced out of the primary transcript or retained (most common in mammals)
- Mutually exclusive exons: only one of two exons is retained in mRNAs after splicing.
- Intron retention: an intron may or may not be spliced out
How is alternative splicing regulated?
A system of trans-acting proteins that bind to cis-acting sites on the pre-mRNA
- Splicing repressors, bind to silencers, ↓ probability that a nearby site used as splice junction
- Splicing enhancers, bind activators = ↑ probability that a nearby site used as splice junction
miRNA
- ~22 bp long
- bind to complementary mRNA areas
- →post-transcription gene silencing
- pivotal in evolution of complexity? by causing innovations?
In all species DNA methylation patterns are..
- dynamic
- variable amond individuals
- conserved within species
Genomic Imprinting
Silencing of one parental copy of each gene, which depends on the sex of the parent from which it was inherited.
non- random silencing
not 50:50 inheritance
why? paternal genes take resources from mother at her expense, benefits genes to know where they come from
Mechanisms by which early enviroment can affect adulthood health
- Thrifty Phenotype
- Maternal effects
- Predictive adaptive responses
- Matching
Why is early environment associated with adult disease?
Genetic effects?
not selected against as did not reduce fitness? (pre-industrial when people dies younger)
WRONG
Why is early environment associated with adult disease?
Correlation between birth and adult environment ?
People who were deprived in early life were also deprived in later life
WRONG
Why is early environment associated with adult disease?
Long-term effects of early environment ?
Cohort effects or maternal effects on intrauterine growth, with downstream effects on adult phenotype
YES
nutrient avalibility affects hormonal control
leads to long term changes
Why does experience in early development permanently affect metabolic function?
- The 1992 thrifty phenotype hypothesis
- Thrifty phenotype as an adaptive maternal effect
- The predictive adaptive response (PAR) hypothesis 4. Matching between maternal and offspring phenotype
The 1992 Thrifty Phenotype Hypothesis
Hales & Barker
“We propose that type 2 diabetes is the outcome of the fetus having to be nutritionally thrifty”
i.e. fetus changes structure and function of tissues because they help it to cope with a reduced nutrient supply there and then
Developing slowly and being small at birth is better than dying !
Thrifty phenotype could be an adaptive maternal effect
Hales & Barker 2001
“The poorly nourished mother gives the fetus a forecast of its post-birth nutritional environment. The adaptations only become detrimental when the postnatal environment and mother’s forecast differ”
i.e. fetus changes structure and function of tissues because they help it to cope with a reduced nutrient supply in the short-term future
The predictive adaptive response (PAR) hypothesis
Gluckman & Hanson 2004/2005
“PARs are induced by environmental factors acting in early life, not as an immediate physiological adaptation, but as a predictive response to expected future environment”
“The induction of PARs will confer a survival advantage in the predicted reproductive enviroment”
i.e. fetus changes structure and function of tissues because they help it to cope with a reduced nutrient supply in the long-term future
adaptive value of insulin resistance in PAR hypothesis?
Reduces energy invested into growth and metabolism
adaptive value of Reduced skeletal muscle mass in PAR hypothesis?
Decreases energetic demands of maintaining adult body and frees up resources for survival and reproduction
adaptive value of Reduced negative feedback in the HPA axis in PAR hypothesis?
Heightened stress response allows greater chance of survival in a nutrient-deprived and predator rich environment
Support for PAR
- Meadow voles: Mothers ‘predict’ thermal environment that offspring will eventually live in
- Dutch famine: short, mismatch, adults have impared glucose tolerance. Siege of Leningrad: long, match, no impared tolerance
Problems with PAR hypothesis
things can change in lifetime!
Matching between maternal and offspring phenotype
Wells 2007
“The thrifty phenotype has been favoured due to its capacity to improve the fit between offspring and maternal phenotypes, and represents a mechanism to maximise maternal, rather than offspring, fitness”
i.e. fetus changes structure and function of tissues so that its metabolic demands will match that which its mother can provide
Environmental ‘matching’ predictions of the different hypotheses
Silver spoon
- no matching- fitness always improves with enviroment
- those born in good cond. always do better
- evidence: choughs
how to Conduct Experiments to test PAR
- Chose your metric of early condition (food, density, competition, predation)
- Notice, most studies either increase or decrease ingredients, not both…think of Dutch and Leningrad famines. Can you manipulate both?
- How does your experiment isolate your ingredient, without impacting other possible ingredients?
Why Should Phenotypes Be Plastic?
- Efficient allocation of nutrients and energy
- Traits can be costly when not needed
- Consequences of having traits when needed are predictable
- Needs are unpredictable in time and space, plasticity allows adaptation when/where needed?
problems with the modern synthesis
- How do plastically complex traits arise from genes selected for a given trait get constructed during evolution?
- How does genetic responses to environment evolve
poly-modality
If random mutation and selection represent the main evolutionary driver, how can big changes in phenotype evolve so quickly? And how can you get big differences in phenotype without differences in genotype?
•the lack or constraining force of development
extended synthesis
Natural selection can only affect genes that are expressed and have measurable phenotypic consequences. Genes that are not expressed or are phenotypically neutral have their own evolutionary rhythm. Suggests that selection acts on phenotypes not genes (ie outcomes not input).
Genetic assimilation
the introduction of beneficial genes into existing selection on phenotypes arises through developmental canalization (selection on a single outcome)
