W6L2 Fri human population genetic P2

Question 1

H statistic

Answer 1

H statistics – measurements of heterozygosity and diversity:
* HI – heterozygosity within an Individual
* HS – heterozygosity within a Subpopulation
* HT – heterozygosity across the Total population

Question 2

F statistic

Answer 2

F statistics – measurements of population structure and differentiation:
* FXY describes the correlation between gametes drawn from x relative to y
* eg, FIS describes the correlation (or diversity) between gametes from a single Individual relative to what is seen in the Subpopulation.

Question 3

FST

Answer 3

FST is the most widely used F statistic in population genetics:
* It describes the proportion of the variance due to between-subpopulation (rather than within population) differences.
-FST= Ht-Hs/Ht

Question 4

Cluster vs cline

Answer 4

• human cluster in livable area so analyses of human often yield a smooth, clinal spread of alleles without abrupt discontinuities
  -Cline: smooth distribution of alleles frequencies with respect to geography

Question 5

How can continuos diversity can look discontinuous

Answer 5

• Different analysis methods and collection strategies emphasize different properties of the same dataset.
• Sampling points along a cline can introduce an impression of discontinuity:

Question 6

Ascertainment bias

Answer 6

No panel or resources has sampled all of existing human diversity * This is a type of ascertainment bias
* Ascertainment bias: Distortions in a dataset caused by the way that either polymorphisms or samples are collected.
-Geographic obstacles do present barriers to gene flow
* Discontinuities in sampling exacerbate the impression of separation between populations

Question 7

What is a population

Answer 7

• Discrete population labels are a convenient framework for talking about the underlying biological processes, but grossly simplify the reality of human diversity.

Question 8

What is not a population in human

Answer 8

Genetic ancestry is not synonymous with race or ethnicity!
* Racial categories are social constructs that often fail to correlate with genetically distinct populations.

Question 9

Example of human diversity warfarin

Answer 9

-A blood thinning medicine but highly response to same dose between individual w/ sever side effect if dosed wring
-highly variable response that is stratified by self reported ethnicity
-cause in part by population differences in the presence of multiple SNPs in genes that metabolism the drug

Question 10

The homo origin

Answer 10

-closest relative chimpanzee and bonobos, common ancestor 6-9 Mya
-the homo genus is around 2 myo
-oldest member is homo erectus

Question 11

The homosaian origin

Answer 11

• Homo sapiens is a young species with the oldest known molders skull dated 195Kya
  -did not appear overnight, fossil show mixture of archaic and mordern trait (oldest 315Kya)
• early day unclear but not a single place of origin, rather a sizable network of individuals spread across africa

Question 12

DNA showing our history: method

Answer 12

-early attempts at reconstructing in human demography focused on the Y chromosome and mitochondrial DNA
-both these are non-recombine and uni parental inheritance
-these two loci are assured to evolved neutrally so they are analyzed with coalescence approach with geographical data

Question 13

The global Y-chr phylogeny

Answer 13

-oldest lineage group are African, older lineages are geographically closer to africa than younger one
-clinal distribution mirror geography
-mtDNA look similar, common ancestor 200kya

Question 14

The problem with mitochondrial EVE and Y-chr Adam

Answer 14

-overall picture is correct
-but coalescence of mtDNA and Y0chr depends on sampling and current demograph
-coalesce to only provide information about the history of the thing we look at
-need to look at more loci

Question 15

Learning deep history via genetic

Answer 15

-different migratory pattern of population movements leave different traces on the genomes of population
-the island model, all population exchange migrant w each other
-in the stepping stone, only exchange with geographic neighbor
-answer this by calculating FST between pairs of global population

Question 16

Pairwise FST in HGFP-CEPH population and migratory method

Answer 16

-data overwhelming support stealing stone human migration model
-very strong isolation by distance, population tend to exchange alleles with population geographic proximity

Question 17

Heterozygousity in global pop

Answer 17

-human group outside of africa contain only a small subset of all African genetic variation
-strong evidence of genetic bottleneck and a founder effect in migration out of africa

Question 18

How many bottle neck

Answer 18

-continuos decrease in diversity as distance increase indicate that many bottleneck as humans spread through the world, the serial founder effect model

Question 19

Genetic drift and effect on the human initial population

Answer 19

-change in allele frequencies due to random sampling across generations
- the bottleneck are exacerbated by genetic drift

Question 20

How alleles frequency distribution contain information about population history

Answer 20

-Individuals and populations did not stop acquiring mutations once they exited Africa.
* The distribution of worldwide derived allele frequencies suggests one more dramatic demographic process following the OOA exit:
Recent, large scale, human expansions (worldwide)
-When a mutation was seen only Twice in the entire panel, both copies were overwhelmingly in a single group, or in geographically close groups.

Question 21

Admixture

Answer 21

• Populations that split do not always remain separate.
• Coming together after a long period of isolation to form a hybrid population is known as admixture
• This can be a sex-biased process
• Contributions of two parent pops do not have to be 50/50
• Admixture can be identified on the basis of LD linkage disequilibrium patterns, especially if the two parent populations can be sampled.

Question 22

History of admixture

Answer 22

Admixture has been a feature of human history for 10,000s of years.
* Colonialism and the trans-Atlantic slave trade are recent examples.
* Potentially exposes allele combinations to novel genetic backgrounds

Question 23

Effect of natural selection on human

Answer 23

Natural selection continues to shape human populations, but ongoing selection is much harder to spot than past selection.
* Selection’s impact on the genome changes over time.
*No single method can detect both recent and ancient selection.

Question 24

The low hanging fruit: de novo sweeps

Answer 24

• The easiest selective event to detect is a recent (> 50,000 years) hard sweep from de novo variants.
• An advantageous mutation arises once through mutation and rises quickly in frequency in a population, as does its associated haplotype.

Question 25

Soft sweeps on standing variation

Answer 25

• Soft sweeps are similar to hard sweeps, but the selected variant was already present in the population, and often associated with more than one haplotype.
• Depending on the starting frequency, this can make soft sweeps harder to detect

Question 26

Polygenic adaptation

Answer 26

• Most complex traits are polygenic/omnigenic
• In these cases, it seems likely that selection will act to shift allele frequencies across multiple loci simultaneously
  This can be very hard to differentiate from random drift acting on population structure, so we do not have any great examples yet

Question 27

Gene culture co-evolution

Answer 27

• Culturally-mediated behaviours can drive adaptative change.
• Best known example is lactase (LCT) persistence, the ability to digest milk in adulthood.
  This trait has evolved multiple times worldwide, always in association with dairying and pastoralism.

Question 28

Other example of gene culture evolution

Answer 28

• FADS2 in Inuits: associated with limited cardiovascular impact of a high fat, low carbohydrate diet.
• Copy number variation in AMY1 is associated with historical access to high or low starch diets.

Question 29

Convergent adaptation to high altitude

Answer 29

-Humans have successfully colonised multiple high
altitude (>2500m) environments: the Himalayan plateau, the Ethiopian highlands and the Andean altiplano.
* Populations from these regions show strong evidence of convergent adaptation to the challenges of life at high altitude.
* decreased oxygen availability causes chronic mountain sickness
* blood viscosity increases, impacting cardiovascular health
* very dangerous, especially during pregnancy/child birth – so a very strong selective pressure!

Question 30

Hypoxia Inducible Factors

Answer 30

• The HIF pathway becomes activated during hypoxic exposure.
• Multiple genes in the pathway show evidence of selection in Tibetan and Ethiopian groups
• Andeans are a bit different.
• These groups have a blunted physiological response to hypoxia, enabling them to live successfully at high altitude.
• This mechanism suggests a possible avenue of treatment for some blood thickening disorders