Population genetics Flashcards
Objectives
- To understand the development of the human species and its diversification across the world
- Through an understanding of human genetics in these populations, appreciate naturally occurring genetic differences among humans
- Understand the evolutionary forces that determine and change that composition
- Gain an understanding of population genetic theory relevant to DNA profile evidence
Timelines (dont need to know just to be aware)
What are the different sources of information for ancient populations?
- Rocks
o 4000 Mya - Fossils – rare
o 7 Mya - Archaeological artefacts – tools, pots, ornaments
o 2.5 Mya - Ice core – isotopes and gases
o 1 Mya - DNA – ancient DNA and living genomes
o 200 Kya - Languages
o 3 Kya
What are some of the issues of gathering DNA from fossils?
- Availability of material limited
- Difficulties of analysis
What are some of the strategies for getting DNA from fossils?
o Proteomic analysis (Mass Spectrometry- used more recently)
o Prevent modern contamination
o Detect and quantify modern contamination
o Consistency with ancient DNA
o Reproducibility
What are pre-modern humans known as?
**Homo erectus **
What are some potential archaic movements between 1.9-1.2 Mya?
- Earliest hominids seen in eastern part of Africa where they spread from there. Moved due to food, fertile ground, etc.
- Nevertheless, most people agree that there was an exodus from Africa of homo erectus type species to occupy much of the rest of the old world from East African about 1.9 MYA using two different routes – up the Nile Valley into Israel and also across the Red Sea into the Arabian Peninsula, arriving in SE Asia about 1.7MYA (with the appearance of Java Man) but not arriving in Europe until 1.2 MYA
What are the 4 different origin models?
A - Out of Africa- Homo erectus starts in Africa and continues with some development over time. When Homo erectus moved into these different continents they die out and a new species then develops which later forms Homo sapiens. This theory has more favour than D but still doesn’t answer all the questions
B – Metapopulation model (fission, fusion, gene flow, local extinction)- Homo sapiens develop but Homo erectus influence homo sapiens through development of their own
**C – trellis theory- **The idea that there was an exchange of material between continents
D – pure multiregional hypothesis- start in Africa then eventually move into the other continents. They all develop independently of each other in each location
What is some support for the ‘Out of Africa’ replacement hypothesis?
* Multiregional model – Homo erectus to Homo sapiens occurring in different places at different times – requires extensive gene flow
* Genetic diversity higher in Africa
o This suggests there is a longer evolution / larger population
* MtDNA and Y phylogenies have root in Africa
o MtDNA 160 KYA (mitochondrial eve which was the ‘first’ woman is what it is dated back to)
o Y chromosome 140 KYA – 500 KYA
* Human anatomical features 130 KYA Africa / 50 KYA rest of World
* neandertals and Denisovans were prior to modern human development and the red lines show the % linkage between these populations
Tell me about European spread
- 40 Kya – little influence as before the last ice age 11Kya
- 6 Kya mass migration of farmers (orange) from fertile crescent mixing with Neolithic hunter-gatherers (blue)
- Structure plot 4.5 – 3 Kya
- Established view – also that they spread the Indo-European languages
Bronze age- Yamanaya Herders 2 Kya
* Steppe pastoralists- herders, travelled on horse so could travel long distances
As forensic scientists what do we learn from both the modern and ancient population genetics?
How is DNA inherited?
- Individuals inherit half their DNA from one parent and one from the other
* RECOMBINATION produces new DNA strings by combining the two parental strings
o Each of our chromosomes is a mosaic of those from our parents - Chromosome sequences are very similar
o About 1 per 1000 bases differs between pairs of chromosomes
What is in our DNA?
* Genes – less than 2% of total DNA
o Approx. 35,000 in humans
o As forensic scientists we don’t have to look at these due to privacy reasons
* Pseudogenes
o Ancient genes that have lost their coding ability
o Arisen because of multiple mutations within a gene whose product is not required for survival
* Promotors and enhancers
o Sequences that control gene expression
* Repeat DNA
o Packaging and spacer sequences
o Separate genes
o What forensic science really focuses on
**
* NUMTS (nuclear mitochondrial DNA)**
o Fragments of mitochondrial genomes inserted into eukaryotic genomes
How does variability occur between humans?
Why is this often a complex topic?
- There are noticeable differences between people
o Difference in phenotype
o Due to difference in genotype - Gender, height, weight, skin colour, eye colour, hair colour, age
- Often complex
o Can be due to genetic / environmental / variable developmental and molecular processes / human intervention - Vitamin D is the key to skin colour as it is essential, too much leads to cancer and too little can make someone infertile so races are primarily due to vitamin D levels. different mutations between Europe and Asia for e.g., in skin colour
Provide the definition for the following:
**Allele
Polymorphism
Mutation
Allele frequency **
* Allele
o One of several different forms at the same locus
* Polymorphism
o Two or more alleles of a gene or other DNA sequence in a population
* Mutation
o A variant allele that occurs in less than 1 percent of the population
* Allele frequency
o The proportion or frequencies of each allele in a genetic population
Nomenclature
Phenotype and genotype frequencies
Genotype frequencies to allele frequencies
Hardy Weinburg equation
Dominant and recessive phenotypes
- Phenotype does NOT reveal the genotype
- Black sheep – gene for black wool is a recessive gene
o White/White genotype
White phenotype
o White/Black genotypes
White phenotype
o Black/Black genotype
Black phenotype
- How many are heterozygotic?
White sheep- what percentage have black genes?
- Phenotype is black or white
- Black is recessive
- What % of the sheep are heterozygotes?
o 4/16 (black) = 0.25 = q2
o q = 0.5
o p = 1-0.5 = 0.5
o 2pq = 2 x 0.5 x 0.5 = 0.5 = 50%
Cystic Fibrosis is an
* Autosomal recessive condition
* Prevalence 1 in 2500
* How many people are carriers?
- Autosomal recessive condition
- Prevalence 1 in 2500
- How many people are carriers?
o Freq(CF/CF) = q2
o q = 0.0004 = 0.02
o Freq(N/N) = p2
o p = 1-q = 0.98
o Freq(CF/N) carrier – 2pq = 2x0.98x0.02
o =0.0392 = 1 in 26 individuals are carriers
Spotted moths
- Moth spotting is controlled by a single gene with two codominant alleles: W and B
- Spotted moths have 3 phenotypes – white spotted (WW), grey spotted (WB), black spotted (BB)
- A population census recorded 22 white, 216 grey and 492 black moths
- What is the frequency of the W allele?
Hardy Weinburg disequilibrium
Populations may not always be in HWE because of factors changing genotype or allele frequencies such as;
o Genetic drift and gene flow
o Non-random mating
o Natural selection
o Mutations
- Frequencies of blood group phenotypes very different, but are they in HWE?
An exmaple of using the Chi squared test
What are some factors affecting genetic variation and the subfactors
How does recombination increase diversity?
Sexual reproduction results in meiotic recombination
o Generates new combinations of alleles (haplotypes) on same chromosome pair
o Diversity will be increased
o Enables populations to adapt to their environment by combining advantageous alleles
o Fast way to assemble the fittest genotype
What is the linkage equilibrium and what does it assume?
- Assume two loci on one chromosome
- Each has two alleles **Aa **or Bb
- If the alleles at each locus are inherited independently then the chance of finding allele a and b together on the chromosome is the product of their relative frequencies
- The loci are in linkage equilibrium
How does genetic drift decrease diversity?
- Random change in allele frequencies across generation
o Population of 10 with blue and green alleles randomly double to produce 10 copies. Frequency of the blue allele – 0.5
o Binomial theorem predicts blue copies with mean 5, sd = 1.6
o If, by chance, 2nd generation blue = 7 then third generation predicts blue copes with mean 7, sd = 1.4
o Number of blue individuals shows drift and eventually there will be fixation at blue, or green - Drift inversely proportional to population size
Population drift illustration
What is meant by fixation and what is the average time to fixation in generations?
Tell me about population size variation
Explain what is meant by balanced selection models
Fitness leads to balanced selection, maintaining diversity
* Heterozygote advantage
o Immune response – MHC variation
o Sickle cell allele deleterious but gives significant survival over malaria
* Frequency dependent
o Rare type has advantage over common type
o Dynamic process
o Maintenance of 50:50 sex ratio
Rare sex becomes fitter as always able to mate
o Left handedness more common in males engaging in interactive sports
Male-male fighting advantage
Diversity can also be manipulated via migration, explain how
- Only changes allele frequencies within a sub-population
- Diversity measured through **FST **
- The greater migration (m), the lower FST, and the lower diversity will be within a sub-population
- Migration tends to homogenize differences between populations
What is meant by Patrilocality and Matrilocality
What does this influence?
- Differential movement of men or women
- Patrilocality – women move to where men live – area shows higher MtDNA diversity
- **Matrilocality – **men move to where women live – areas show higher Y chromosome diversity
- Social behaviours influence genetic diversity
Our genealogical ancestors are not necessaily our genetic ancestors
Who do you think you are?
- We all share common ancestors remarkably recently
- Someone living 3-5 thousand years ago (Bronze age) is common ancestor of everyone alive today
- Just a few thousand year’s earlier we all share the same set of ancestors
- Common ancestry dates will be more recent for those who are less distant – on the same continent
Different company tests: what does it mean?
Global predictions from root populations
