Evolutionary Genetics Module 2
Topic 1 Lactose Persistence and Selection
- Some genes change quickly in a pop compared to others – some change purely
based on size
What is Evolutionary Genetics?
- Broad field of studies that examines evolution in terms of changes in gene and
genotype frequencies within populations and the processes that convert the
variation within populations into permanent variation observed between species
- Why do some populations have a phenotype in a high or low proportion?
- Patterns of relatedness and variation first seen in animals by Darwin
- Balance between:
o Mutation, migration, random genetic drift AND
o Purifying selection (bad) and Positive selection (good)
Positive Selection/Adaptive selection = chance mutations that are beneficial and
increase in prevalence in a population
- Fitness increase does not need to be 100%
Purifying Selection = mutations will be lost very quickly in the population
Lactase Persistence (enzyme persists in genetics)
- Lactase = enzyme
- Lactose = main sugar in milk broken down by lactase into galactose and glucose
– then absorbed into bloodstream and cells
- Breakdown occurs in small intestine
- Without enzyme?
o Disaccharide continues from small intestine to large intestine
o Broken down in colon via fermentation leading to gas production
(methane, CO2), bloating, leads to osmotic imbalances (draws water out
of blood stream, low blood pressure), diarrhea
o In the colon, fermentation of lactose leads to:
§ Short chain fatty acids
§ Methane
§ Hydrogen
§ CO2 production
Lactase Persistence is NOT Ancestral
- Most modern humans = lactose intolerant
o Lactase genes turned oY
- Lactose persistence = result of plant/animal domestication
o Dairy = new food source
o Cows and grasses/grains
- Lactase biosynthesis regulation after weaning determines lactose intolerance vs
lactose persistent
, o As a species, lactase gene is active in infants (only source of nutrients =
breast milk) and then usually turned oY
- Some populations have lactase persistence mutations
o Keep the lactase gene switched on
o Retain the ability to digest dairy
o Turning genes on/oY?
§ Mutate gene structure
§ Mutate core regulatory element
- Lactase persistence mutations are adaptive and subject to positive selection
o Individuals carrying mutation have an alternative nutrients source à
better for survival à pass to children
o Can increase reproductive fitness even slightly
How Common is Lactose Persistence?
- Most European and some African populations can digest lactose
o 80% of European populations
§ Bottleneck population
§ Very homogenous
- Largely northern hemisphere
*selective sweep à like a wave
à complete selective sweep = complete replacement of wt gene with mutated one
Domestication of Cattle Led to Lactose Persistence
- Alleles conferring lactase persistence became prevalent in human societies
AFTER cattle domestication and constant milk supply
o Constant milk – selects for lactase persistence in adults
o Rapid spread of lactose persistence allele
- Lactase persistence linked to 2 SNPs in lactase gene in European populations
o C/T- 13910 and G/A – 22018
§ SNP 13910 aYects TF Oct1 binding and results in more lactase
mRNA
- Paper concludes lactose persistence is a result of selective sweep spanning
roughly 1 million BP of DNA
Lactase Gene and a Selective Sweep
- LCT (lactase) gene is on Chr2
- ~55 000 bp
- Translated into protein of 1927 aa
- LCT mutations associated with lactase persistence a9ect binding ability of
transcription factors (eg Oct 1) to promotor region
o Transcriptional control is over long distances!
- Selective sweep:
o Quick change
o Some regions of DNA are identical and kept identical because these
mutations would decrease survival or be lethal
o Large blocks of genome organization are the same
, o Chance mutations may occur that are beneficial to survival/reproductive
fitness
§ Selective pressure is placed on the region
§ Areas of genes with a specific mutation are kept the same to keep
the positive mutation in future individuals
§
NB NOTE.
- Origin of modern humans = recent
- Origin of modern humans = Africa
- Early human populations =
o Small
o Subject to genetic drift
o Under many selective pressures
Linkage Disequilibrium and SNPs
- Linkage disequilibrium = non random association of alleles at diYerent loci
o 2 genes in linkage disequilibrium à certain alleles of each gene are
inherited together more often than would be expected by chance
o Generally indicative of combinations of alleles at the two loci aYecting
viability of potential oYspring
- SNPs = DNA variants present in the population
o Alternate allele is present in at least 1% in the population
o Most SNPs are selectively silent
o Can generate haplotypes
TichkoJ Paper Study: Convergent Adaptation of Human Lactase Persistence in
Africa and Europe
- LP (lactase persistence) recap:
o 80% of European populations and linked to 2 SNPs
o Lactase mRNA regulated by cis acting elements on the LCT promotor
o Result of a selective sweep
o Lactose intolerance is ancestral in modern human adults
- Questions?
o Do African LP populations have same or diYerent SNPs as European
populations
o When did African SNPs arise
o What selective forces were responsible
- TichkoY et al knew:
o Two SNPs were in linkage disequilibrium in Finnish populations
§ C/T 13910 and G/A 22018
• Had 97 t 100% association with LP in Finnish populations
• Had high (80%) with other LP European populations
• Absent in most Africa LP populations
Topic 1 Lactose Persistence and Selection
- Some genes change quickly in a pop compared to others – some change purely
based on size
What is Evolutionary Genetics?
- Broad field of studies that examines evolution in terms of changes in gene and
genotype frequencies within populations and the processes that convert the
variation within populations into permanent variation observed between species
- Why do some populations have a phenotype in a high or low proportion?
- Patterns of relatedness and variation first seen in animals by Darwin
- Balance between:
o Mutation, migration, random genetic drift AND
o Purifying selection (bad) and Positive selection (good)
Positive Selection/Adaptive selection = chance mutations that are beneficial and
increase in prevalence in a population
- Fitness increase does not need to be 100%
Purifying Selection = mutations will be lost very quickly in the population
Lactase Persistence (enzyme persists in genetics)
- Lactase = enzyme
- Lactose = main sugar in milk broken down by lactase into galactose and glucose
– then absorbed into bloodstream and cells
- Breakdown occurs in small intestine
- Without enzyme?
o Disaccharide continues from small intestine to large intestine
o Broken down in colon via fermentation leading to gas production
(methane, CO2), bloating, leads to osmotic imbalances (draws water out
of blood stream, low blood pressure), diarrhea
o In the colon, fermentation of lactose leads to:
§ Short chain fatty acids
§ Methane
§ Hydrogen
§ CO2 production
Lactase Persistence is NOT Ancestral
- Most modern humans = lactose intolerant
o Lactase genes turned oY
- Lactose persistence = result of plant/animal domestication
o Dairy = new food source
o Cows and grasses/grains
- Lactase biosynthesis regulation after weaning determines lactose intolerance vs
lactose persistent
, o As a species, lactase gene is active in infants (only source of nutrients =
breast milk) and then usually turned oY
- Some populations have lactase persistence mutations
o Keep the lactase gene switched on
o Retain the ability to digest dairy
o Turning genes on/oY?
§ Mutate gene structure
§ Mutate core regulatory element
- Lactase persistence mutations are adaptive and subject to positive selection
o Individuals carrying mutation have an alternative nutrients source à
better for survival à pass to children
o Can increase reproductive fitness even slightly
How Common is Lactose Persistence?
- Most European and some African populations can digest lactose
o 80% of European populations
§ Bottleneck population
§ Very homogenous
- Largely northern hemisphere
*selective sweep à like a wave
à complete selective sweep = complete replacement of wt gene with mutated one
Domestication of Cattle Led to Lactose Persistence
- Alleles conferring lactase persistence became prevalent in human societies
AFTER cattle domestication and constant milk supply
o Constant milk – selects for lactase persistence in adults
o Rapid spread of lactose persistence allele
- Lactase persistence linked to 2 SNPs in lactase gene in European populations
o C/T- 13910 and G/A – 22018
§ SNP 13910 aYects TF Oct1 binding and results in more lactase
mRNA
- Paper concludes lactose persistence is a result of selective sweep spanning
roughly 1 million BP of DNA
Lactase Gene and a Selective Sweep
- LCT (lactase) gene is on Chr2
- ~55 000 bp
- Translated into protein of 1927 aa
- LCT mutations associated with lactase persistence a9ect binding ability of
transcription factors (eg Oct 1) to promotor region
o Transcriptional control is over long distances!
- Selective sweep:
o Quick change
o Some regions of DNA are identical and kept identical because these
mutations would decrease survival or be lethal
o Large blocks of genome organization are the same
, o Chance mutations may occur that are beneficial to survival/reproductive
fitness
§ Selective pressure is placed on the region
§ Areas of genes with a specific mutation are kept the same to keep
the positive mutation in future individuals
§
NB NOTE.
- Origin of modern humans = recent
- Origin of modern humans = Africa
- Early human populations =
o Small
o Subject to genetic drift
o Under many selective pressures
Linkage Disequilibrium and SNPs
- Linkage disequilibrium = non random association of alleles at diYerent loci
o 2 genes in linkage disequilibrium à certain alleles of each gene are
inherited together more often than would be expected by chance
o Generally indicative of combinations of alleles at the two loci aYecting
viability of potential oYspring
- SNPs = DNA variants present in the population
o Alternate allele is present in at least 1% in the population
o Most SNPs are selectively silent
o Can generate haplotypes
TichkoJ Paper Study: Convergent Adaptation of Human Lactase Persistence in
Africa and Europe
- LP (lactase persistence) recap:
o 80% of European populations and linked to 2 SNPs
o Lactase mRNA regulated by cis acting elements on the LCT promotor
o Result of a selective sweep
o Lactose intolerance is ancestral in modern human adults
- Questions?
o Do African LP populations have same or diYerent SNPs as European
populations
o When did African SNPs arise
o What selective forces were responsible
- TichkoY et al knew:
o Two SNPs were in linkage disequilibrium in Finnish populations
§ C/T 13910 and G/A 22018
• Had 97 t 100% association with LP in Finnish populations
• Had high (80%) with other LP European populations
• Absent in most Africa LP populations
