Population Genetics Flashcards
Hardy Weinberg
Chance of a p sperm fertilising a p egg? p x p=p^2
Chance of a q sperm fertilising a q egg? q x q=q^2
Chance of a p sperm fertilising a q egg? p x q = pq
Chance of a q sperm fertilising a p egg? q x p = pq
Overall ratios of the zygotes arising from fertilisations giving rise to the three genotypes at this locus will then be:
AA Aa aa
p2 2pq q^2
A Hardy Weinberg population is an ideal population that assumes allele frequencies do not change over the generations. There are many factors which lead to a deviation in Hardy Weinberg.
H-W rules
- populations in H-W are stable and do not change:
- magine island founded by 100 homozygous people; two shipwrecks from two countries; one are all albinos, the other not. What happens? 60 of the survivors normal coloured, and 40 albinos, i.e., frequency of A = 0.6 and a = 0.4. Mate at random
According to H-W, the frequency in the next generation of AA will be 0.36, of Aa 0.48 and of aa 0.16 (so that only 16% of the population are actual albinos).
Genotype frequencies have changed (although allele frequencies have not). Will stay stable forever, unless something makes them
change.
H-W makes it possible to work out the frequencies of dominant homozygotes and heterozygotes from the frequency of recessives. If 0.16 of the population are albinos aa (q2), frequency of a allele is square root of this = 0.4. Freq of p allele is 1-0.4 = 0.6, so 2pq is 2 x 0.4 x 0.6 = 0.48
What changes H-W equilibrium
Hardy-Weinberg populations is a sort of null model – a bit like a ‘perfect gas’ in physics. Many things can change it and will explore these over the remainder of this lecture and in Lectures 17-18:
Natural selection: H-W assumes that all genotypes have the same fitness. Obviously, not true. Imagine a recessive lethal when homozygous; exposed to a selective disadvantage, s, of 0. What are the allele frequencies in the next generation?
If frequency of q is 0.8, and it is q lethal recessive, the frequency in the next generation will be
0.8/1.8 = 0.44 – quite a big drop. If frequency is 0.1, then in the next generation, for a recessive
lethal, the frequency of a is 0.1/1.1 = 0.099; which is a much slower decline.
This means selection takes a long time to get rid of rare recessives – 100 generations (time since
Roman Empire for humans) to reduce the frequency of a recessive allele from 1 in 100 to 1 in 200.
Also takes long time for a new recessive to increase in frequency, but much shorter for a new dominant. Genes for insecticide resistance are often dominant.
Examples of natural selection
Classic example is the spread of super bugs such as Methicillin-resistant Staphylococcus aureus
(MRSA) which arose around 1997. Best way to control the spread of the disease is effective hygiene. Similarly, insecticide resistance in pest species such as houseflies. The introduction of non-native species into new habitats, often by humans (for example Drosophila subobscura)
Many examples of natural selection in humans – geographical variation lactase persistence. In many populations, such as individuals from South east Asia, lactase becomes deactivated as we mature. In Europe and America though, many individuals are able to digest milk as adults. This difference probably arose because in the middle east populations begun to keep cattle around 7500ya. These individuals spread to Europe. Similar patterns are observed in alcohol tolerance. Many of the world’s top long-distance runners are Africa.
One group the Kalenjin have many
different adaptations which enable them to absorb more oxygen.
Founder effects
A loss of genetic variation caused by a large population arising from a small number of individuals coming from a larger population.
For example, connexin deafness allele arrived in a
Himalayan village and is today quite prevalent. Similarly, populations of Drosophila subobscura, a European population of Drosophila introduced into the Americas all arose from a single vial
introduced. A large population has formed from this small population.
Bottlenecks
The loss of genetic diversity caused by a large reduction population size (say a natural
disaster). Alleles in the population are randomly lost.
Genetics drift
Random change in allele frequencies caused by random sampling. Genetic drift is greatest in small populations; strength of effect depends on how small the population size and the allele frequencies.
Sampling standard deviation
We can quantify the sampling standard deviation (ie the strength of drift) using the formula √pq/2N
(p and q are allele frequencies, N is population size). This means the larger the sample size, the
smaller the sampling variance.
Similarly, the closer p and q is to 0.5, the smaller the sampling variance.
“N”, though, has a historical component – past bottlenecks can reduce it even if the population is large today.
Example of genetic drift
Many examples of genetic drift. It can be demonstrated in a lab by maintaining 2 populations of red and white eyed Drosophila in a cage and measure changes in the frequency of the phenotype.
Eventually one colour always goes extinct. Smaller populations take a shorter time for an eye phenotype to reach extinction. It takes longer for an eye phenotype to reach extinction when p=0.5.
Bottlenecks, founder effects, drift and migration example
Bottlenecks, founder effects, drift and migration are closely related. The human population of the
island of Tristan de Cunha arose from a small number of individuals (founder effect). The population has gone through population crashes (bottlenecks). Individuals from this population have travelled to other parts of the world such as Southampton, UK (migration). The population has the highest incidence of retinoblastoma, a type of eye cancer.
Invasive species and loss of diversity (humans)
Invasive species have all undergone founder effects and a loss in genetic diversity, including of
course humans. Genetic diversity in humans negatively correlates with the distance from Addis
Ababa.
Similarly, in languages populations further from Africa have fewer sounds. Our parasites such
as malaria sees a loss of diversity from Africa.
Runs of homozygosity are very common in tribal and religious communities. These communities are founded from a small number of individuals eg the Amish. These populations have high incidences of rare recessive alleles.
Migration
gene flow between populations can bring new alleles to a population. We can see this looking at the origin of different populations in London.
Non random mating (positive assortative mating)
Assumption of the H-W is that mating is random;
clearly not true. Often individuals of the same genotype are more likely to mate, related to
inbreeding. Historically in the USA it was illegal to marry outside your own racial group.
Non-random mating (negative assortative mating)
Mating between individuals who differ in
genotype.
Human migration has led to different races in matings between races. Ancestry painting often shows we are made up of haplotypes from many different geographical populations.
Neanderthals certainly interbred with Homo sapiens and introduced many genetic diseases into our population.
We also find genes from the Denisovans in human populations from East Asians. The Tibetans have a gene from the Denisovans which enables them to absorb more oxygen.
Positive assortative mating
Mating of individuals of a similar genotype or phenotype. Many animals display this including animals such as blue tits who tend to mate with partners of similar brightness.
Humans to show positive assortative mating for traits such as height, weight, collar size, skin colour (although in many places this pattern is breaking down) and one of the strongest predictors of all is educational level.
Negative assortative mating
Mating of individuals of a different genotype or phenotype. Wolves for example are more likely to mate with individuals of a different coat colour. Similarly, in white- throated sparrows opposite morphs (tan and white) always tend to mate.
Prevention of mating
In humans, there are cultural taboos which prevent like-for-like (ie mating between relative)
matings. Sex is a mating of two different genotypes, although some species have more (Paramecium has 6).
Hermaphrodite flowers want to avoid mating with themselves. Multiple alleles act as an
outbreeding mechanism: a x ab (ie a male ‘a’ gamete/pollen lands on a female ‘ab’ diploid style) – fails
b x ab - fails
c x ab - succeeds
Evolution and alleles
Evolution rapidly leads to a diversity in these fertility alleles; wild cherry has around 20. There maybe similar alleles in humans; scent receptor genes. BRUCE effect in mice; if a pregnant female who was impregnated by male mouse from the same inbred line is placed in a cage with a male from a different line (or just containing his urine) she will abort the pregnancy so she can mate with the different male. Rats can determine different human genotypes from the smell of their sweat.
Taysachs and inbreeding
Tay-Sachs disease used to be a major problem in populations of Ashkenazi Jews, but has now
effectively been eliminated by Rabbi Eckstein. Dor Yeshorim is a genetic screening process to avoid
heterozygotes from marrying each other.
Mutation
Allele frequencies will change if new alleles emerge in a population
Mutation rates
Mutation rates in genomes vary. Fibrin clotting mechanism; the blocking peptide has a rapid rate of mutation. In contrast a protein such as haemoglobin or cytochrome C have a very slow rate of mutation.
Whales and mutation
Whales are a good model of evolution by mutation. There is a very detailed fossil record. Excellent fit of the physical record and the DNA record. We can use the rate of change of the DNA to date splits in the family tree. Hippopotami are the closest living relative to the cetaceans.
Diversity of primates
If you look at protein or DNA differences between human races, there is really none at all. In contrast, if you look at the differences between the 4 species of chimpanzees, they are far more genetically distinct from each other despite living in very close proximities.
