L16 - Heritability and non-Mendelian inheritance

Question 1

What is heritability?

Answer 1

Is the proportion of variation in a trait due to genetic differences among individuals

Question 2

How can heritability be estimated pt 1?

Answer 2

Comparing parents and offspring. But parents and offspring often also share environment

Question 3

What is an example of comparing parents and offspring?

Answer 3

Heritability of height. Galton’s rule: regression towards the mean. Concluded, children of tall parents are taller than the average pop but shorter than their parents on average. Children from shorter parents have offspring that are, on average, taller than their parents but shorter than the average population.

Question 4

How can heritability be estimated pt2?

Answer 4

Twin studies, monozygotic twins: genetically identical and (usually) share a similar environment. Dizygotic twins: non-identical (full siblings) and (usually) share a similar environment. Differences between monozygotic twins must arise due to environmental differences. Genetic effects can be estimated by comparing the amount of variation in a trait within monozygotic twins so that in dizygotic twins

Question 5

Twin studies heritability?

Answer 5

Concordance = the proportion in which both members of a pair of twins show a trait (out of the cases where at least one twin shows the trait). E.g. schizophrenia. Studied in 1000mz and dz twin pairs. 0.608 in mz and 0.172 in dz.

Question 6

How can heritability be estimated pt3?

Answer 6

Pedigrees, they can provide a powerful approach for measuring heritability. Pathways of genetic inheritance, measurements of a trait for all individuals. But shared environments can still complicate things. Can do cross-foster experiments in non-human animals

Question 7

What does heritability not tell us?

Answer 7

It doesn’t tell us about to what extent genes impact a trait in one individual. E.g. 90% of my height is due to my genes. Low heritability doesn’t necessarily mean that the trait has no genetic component. Milk yield in cows

Question 8

What does high heritability not necessarily mean?

Answer 8

It doesn’t necessarily mean that the trait is largely genetically determined. High heritability instead estimates the proportion of variation in a phenotypic trait in a population that is due to genetic variation between individuals in that population. If we measure heritability of size within a pop A or B (shared good or poor enviro) it will be high, if we measure heritability of size across very different environmental conditions, it will be low - most effects due to environment.

Question 9

What does heritability not give us a good idea about? and what does it increase?

Answer 9

How a pop may respond to selection e.g. in farming, high heritability = greater response to artificial selection. So if milk yield has low heritability, it is unlikely to increase in response to selection. Heritability can also increase our understanding of the impacts of selection on traits in the wild - but heritability can change depending on the environment.

Question 10

What is cultural inheritance?

Answer 10

Once thought unique to humans, but now accepted to be widespread in the animal kingdom.

Question 11

Examples of cultural inheritance - Cranes?

Answer 11

After filial imprinting on the costumed human pilot of a microlight aircraft, young cranes followed the path of this surrogate parent, adopting it as a traditional migratory route.

Question 12

Examples of cultural inheritance - Fruit flies?

Answer 12

Female fruit flies that witness a male marked with one of two colours mating later preferred to mate with similarly coloured males. This behaviour is further copied by others, initiating a tradition.

Question 13

Examples of cultural inheritance - Bighorn sheep?

Answer 13

Bighorn sheep translocated to unfamiliar locations were initially sedentary, but spring migration and skill in reaching higher-altitude grazing grounds expanded over decades, implicating intergenerational cultural transmission

Question 14

Examples of cultural inheritance - Examples of cultural inheritance - Vervet monkeys?

Answer 14

Groups of vervet monkeys were trained to avoid bitter-tasting corn of one colour and to prefer the other. Later, when offered these options with no distasteful additive, both naive infants and immigrating adult males adopted the experimentally created local group preference.

Question 15

Examples of cultural inheritance - Meerkats?

Answer 15

Young meerkats learn scorpion predation because adults initially supply live prey with stingers removed and later provide unmodified prey as the young meerkats evolve.

Question 16

Examples of cultural inheritance - humpback whale?

Answer 16

A humpback whale innovation of slapping the sea surface to refine predation, known as ‘lobtail feeding’, spread over two decades to create a new tradition in hundreds of other humpbacks.

Question 17

Examples of cultural inheritance - Naked mole-rats?

Answer 17

Naked mole-rats calls signify individual identity and colony identity, are learned from other colony members, and seem to depend on the identity of the current queen.

Question 18

Naked mole-rats groups?

Answer 18

They form cooperative groups, living in multigenerational colonies under the control of a single breeding queen. How they maintain this highly organised social structure is unknown. The soft chirp vocalisation is used to transmit info about group membership, creating distinctive colony dialects. Pups fostered in foreign colonies in early life learn the vocal dialect of their adoptive colonies, which suggest vertical transmission and flexibility of vocal signatures. Dialect integrity is partly controlled by the queen: dialect cohesiveness decreases with queen loss and re-emerges only with the ascendance of a new queen.

Question 19

What does GWAS stand for?

Answer 19

Genome wide association study (e.g. genetic loci associated with critical illness in COVID)

Question 20

What could be created (Cultural inheritance?

Answer 20

A second inheritance system - contribute to darwinian evolution by natural selection. Could account for ‘missing inheritance’ - many GWAS studies of human diseases don’t find sufficient genetic effects to explain heritability. Cross-fostering and other carefully designed experiments may be able to detangle genetic and environmental inheritance of information

Question 21

Examples of cultural inheritance - banded mongooses?

Answer 21

In banded mongooses, natural cross fostering occurs. Young banded mongooses inherit their foraging niche from cultural role models, not parents. Cultural inheritance occurs in the first few months of life, but lasts a lifetime.

Question 22

What are epigenetics?

Answer 22

The inheritance of variation beyond differences in DNA base sequence. Changes are inherited by descendent cells and (maybe) descendent individuals. E.g. Dutch hunger winter - Nazis blocked food supply to northern cities in the Netherlands from Oct. Oct 1944 - April 1945. Caused mass starvation. Calorific restrictions happened in the womb had life-long consequences. Obesity, stroke, and cardiovascular disease were much more common in those conceived during the famine. Likely occurred due to epigenetics effects that alter gene expression.

Question 23

What molecular processes lead to epigenetic changes pt1?

Answer 23

Changes in patterns of DNA methylation. The addition of a CH3 (methyl) group to a nucleotide base; usually cytosine in eukaryotes, often when cytosine is next to guanine (both strands are methylated at the C). Called CpG (p = phosphate backbone). 5’ - Cm G - 3’, 3’ - G Cm - 5’. Many CpG sequences form together = CpG islands. Commonly found near transcription start sites. Inhibit transcription factors from binding so RNA polymerase can’t be recruited

Question 24

Epigenetic inheritance - Methylation?

Answer 24

Methylation can be faithfully maintained when chromosomes replicate.

Question 25

Methylation process?

Answer 25

Before replication, DNA is fully methylated at CpG dinucleotide, during rep, new DNA strands are synthesised without methyl groups, after rep, each new DNA molecule will have methylation on one strand but not the other: the DNA is hemimethylated. Methyl groups, attract methyltransferase enzymes, which add methyl groups to the unmethylated strand. resulting in fully methylated DNA

Question 26

What are epigenetic changes responsible for?

Answer 26

Differences in the phenotypes of honeybee queens and workers. Royal jelly suppresses Dnmt3, which normally methylates DNA, leading to expression of genes that encode characteristics of the queen.

Question 27

What molecular processes lead to epigenetic changes pt2?

Answer 27

Histone modifications. Modifications include the addition of: phosphates, methyl groups, acetyl groups, ubiquitin. Can occur at different amino acids on different histones: can create more than 100 potential modifications. Can increase or decrease transcription through modifying chromatin structure. Maintenance/inheritance is not well understood

Question 28

What are epigenetic effects often induced by?

Answer 28

Early life experiences. Can be behavioural. E.g. mother rats lick and groom their offspring, usually while nursing them. More grooming as pups = less fear as adults & reduced stress response. DNA methylation (which impacts on histone acetylation) causes these differences.

Question 29

What molecular processes lead to epigenetic changes pt3?

Answer 29

RNA molecules can be involved, and multiple epigenetic markers often interact e.g. X-chrom0some inactivation. Both the X a and X i chromosomes have the X ist gene. The X ist gene on X i is transcribed into a IncRNA,... which costs X i but not X a. The X ist RNA recruits PRC2, which produces histone modifications on Xi.

Question 30

What is a paramutation?

Answer 30

An interaction between two alleles that leads to a heritable change in the expression of one of the alleles ( the DNA sequence remains unchanged)

Question 31

What is an example of a paramutation?

Answer 31

In a heterozygote, one allele is able to alter another allele, altered alleles are passed down to future generations. Altered alleles are capable of converting other alleles in future. E.g. In paramutation of the b1 locus in corn, a copy of the B' allele converts the B-I allele to B'*, which is identical to the B'. The mechanisms are not fully understood: B' alleles have chromatin in a closed state in the enhancer region, which may reduce transcription of the purple pigment. Small RNAs are probably involved in the conversion of B-I allele to B'*.

Question 32

What is genomic imprinting?

Answer 32

Some genes are expressed more if they are inherited from the father and others if they are inherited from the mother. Male donkey x female horse = mule, Male horse x female donkey = hinny (Both are usually sterile). The average hinny has a smaller stature, shorter ears, stronger legs, and a thicker mane than the average mule. In the mouse brain, 1300 genes show evidence of genomic imprinting

Question 33

What do paramutation and genomic imprinting describe?

Answer 33

Particular forms of heritable epigenetic changes.