Human evolutionary genetics

Question 1

What is population genetics?

Answer 1

Population genetic studies are a branch of genetics that focuses on the genetic variation within and between populations. These studies provide insights into the distribution of genetic diversity, the mechanisms that drive evolutionary changes, and the patterns of inheritance within populations and the evolutionary history of species.

Question 2

How to study evolution genetics? (3)

Answer 2

mtDNA: looking at the mtDNA of organisms to make molecular clocks and for phylogenetic reconstruction (female ancestry)

Human Y chromosomal tree: Using the human Y chromsome for phylogenetic reconstruction as it does not recombine (male ancestry)

Autosomal markers: using autosomal nuclear genes to reconstruct history

Question 3

Benefits of mtDNA for phylogenetic reconstruction

Answer 3

o High copy number per cell
o Small genome (only ~16kb)
o High mutation rate
o No recombination

Question 4

mtDNA as evidence for the out of Africa hypothesis

Answer 4

• In 1987 a study was done comparing a small region of mtDNA from multiple humans from across the globe
• Evidence for out of Africa
  1) Less mtDNA diversity outside of Africa due to population bottlenecks
  2) Molecular clocks placed the deepest node in Africa 173,000 years ago and outside of Africa 52,000 years ago

Question 5

Disadvatages of mtDNA for phylogenetic reconstruction

Answer 5

Looking at a single locus can be misleading as a single strongly advantageous mutation that occures in Africa and spread may create the picture of the Out Of Africa hypothesis

Question 6

Problems/benefits with Autosomal markers

Answer 6

Problem: Recombination disrupts linkage and distrupts the assumption that closely linked markers are inherited together
Benefit: Recombination lead to independence of evolutionary histories of different genes meaning such data provide more robust picture compared to non-recombining markers.

Question 7

Study using mtDNA and Y chromosomes: Women on the move

Answer 7

Comparing mtDNA and Y chromosome DNA shows that women tended to move greater distances than men in the past probably due to patrilocality (moving to the husband’s home)
With increased distance, Y had an increased Fst but Y mtDNA did not showing that there was an increased difference between population with increased distance in men (less moved meaned less genetic mixing).

Question 8

Limited timescales these studies

Answer 8

Time scale is limited to the most common recent ancestory
- Mitochondira: 200 thousand years ago
- Other nuclear sequences: up to 1 million years ago

The methods do not always agree (Inbreeding in Neanderthals)

Question 8

Advatages of Ancient DNA

Answer 8

Ancient DNA is highly informative – reveals the origins of already extinct species and populations

Question 9

Disadvantages of Ancient DNA

Answer 9

o Highly degraded and fragmented
o High risk of contamination with modern DNA
o Most sequenced samples are quite “recent”: <100KY (oldest sample sequenced is ~400KY)

Question 10

Ancient DNA analyses example:
Inbreeding with neanderthals
Discovery of the Denisovans
Densocan and Neanderthal hybrid

Answer 10

Ancient DNA has been used to study whether the ancestors of modern humans interbred with Neanderthals and other “archaic” hominids. Hybrids only found in Europe.

This evidence can only be seen in nuclear genome analyses and not mtDNA analyses

Question 11

How to see adaptive evolution in DNA sequence data

Answer 11

1) DNA polymorphism

• Selection leaves footprints in DNA polymorphisms
• The spread and fixation of an adaptive allele results in loss of genetic variation around the target of selection.
• The less recombination, the larger the size around the target.
• Gene for lighter skin colour shows less heterozygosity in Europenas than non-europeans

2) Biased allele frequency

• A selective sweep reduces the genetic diversity of that allele within a population
• New alleles/ polymorphism will therefore be at an unusually low frequency when they form
• The Tajima’s D statistic will be shifted to negative values

Question 12

Recent adaptive evolution: Environment

Answer 12

Skin colour: Skin colour is adapted to the environment

• Dark skin provides protection against UV as reduced photlysis of folic acid in high UV environments
• Light skin helps to create Vitamin D3 where there is low UV exposure

The gene responsible for light skin has a lower heterozygosity in Europe compared to non-european countries

Question 13

Recent adaptive evolution: Diet

Answer 13

Lactose intolerance:

• Adults in many populations develope lactose intolerance
• In populations where there was a lot of dairy farming, the ability to digest milk was advatageous and selected for
• This adaptation left characteristic footprints in the lactose tolerance gene: (moderately) reduced variation, biased frequency spectrum and very long derived haplotypes.

Question 14

Signature of local adaptation: population differentiation

Answer 14

• Adaptation to contrasting conditions (e.g. high/low altitude) leads to the spread and fixation of different locally adaptive alleles in the populations, which creates the signal of population differentiation at the genes under selection.
• This can be quantified by the Fst value
• Fst = [Ht – Hs]/Ht, where Ht is total heterozygosity across all populations and Hs is average heterozygosity within subpopulations
• Greater Fst means greater differentiation between populations

Example: Tibetans
- Tibetans have high Fst value for ERAS1 gene which is responsible for regulating the response to hypoxia
- This gene originated by the introgression from Denisovans

Question 15

Overview

Answer 15

The origins of humans is a key example of where evolution genetics has been used to uncover history

Evolutionary genetics is studied by looking at mtDNA, Y chromosome and Nuclear DNA.

Ancient DNA must be studied to look at Extinct species

Adaptive evolution can also be studied by looking at DNA polymorphisms and biased allele frequencies. Adaptive evolution can be seen in response to diet and environment in humans.

Populations also become locally adapted and this can be measured using FST.