Evolution of Gene Regulation
How to measure gene regulation
RNA sequencing (RNA-Seq)
1. Isolate mRNA from tissue of interest
2. Sequence all mRNA in sample
3. Count number of sequences mapping to each gene = expression level
Map RNA sequences to underlying genome
What does gene regulation give us?
Permits organismal complexity
- One genome can encode for multiple tissue types: different genes expressed in
different parts of the flower (heat maps show gene expression levels in
different tissues)
- How did flower complexity evolve? Hierarchial clustering. Similarity of 2 tissues
between the species
Eg. carpal tissues similar transcription patterns
- For example 98% of transcriptional output of humans is non-coding: RNAs and
introns serve as regulatory (Mattick, 2001) read!
Changes in gene regulation allow for adaptive evolution
- Gene expression changes underlie some
adaptive traits
- Example: beak size in Darwin’s Finches varies
among species and key to ecological niches
(Mallarino et al., 2011)
High interspecific gene flow, high
morphological diversity entirely due to gene
regulation high BMR = pointier, wedge-like
phenotype
- Organisms adapt to environmental changes through the fixation of mutations
that enhance reproductive success
- E.coli adapts to different growth conditions by fine-tuning protein levels (Babu
and Aravind, 2005) – predicted the cost and benefits of producing LacZ when no
lactose was present in the medium
Grew E. coli in different conditions (low, medium, high concentrations of lactose
over many generations) after ~500 generations, cells evolved state in which they
expressed LacZ at levels predicted by cost-benefit optimisation model
Cells grown in low lactose concentrations ceased lacZ expression by introducing
deletion near promoter
, Medium expressed moderate amounts of enzyme, high = high lacZ mutations
in coding region which altered mRNA/protein stability/modified rate of protein
translation
Mechanisms of transcriptional regulation
Cis-regulation = on same side as Trans-regulation = beyond
Region of DNA that regulates Region of DNA that regulates
expression of genes on the same expression of distant genes:
chromosome, chromosome arm or transcription factors or signalling
neighbourhood genes
Often cis-regulatory elements are Often trans-regulatory elements bind
binding/sites for trans-acting factors to cis-regulatory sites
Enhancers cannot initiate but increases
existing transcription level
Changes in cis recognition sites can
increase/decrease binding affinity of
repressors
Though not all gene expression change is
adaptive
Global patterns of gene expression
Gene expression regulation evolution: as genomes
between chimps and humans are highly similar
phenotypic difference due to regulation
Across 5636 genes, expression divergence across
amniotes roughly clock-like
- Over several species, steady decline in almost all
tissues – not all regulation is adaptive,
decay due to drift testis have the
fastest change (Brawand et al., 2011)
- Suggests most change is due to genetic
drift
Partition genes into different categories
based on variance
- Genetic drift drives force in gene
expression regulation
, - So evolution but most is neutral, with no adaptive strength
- Purifying selection: any variation is deleterious is removed in all cases
- Positive selection (eg. in cerebellum): deleterious mutations are still removed,
but in some species they are selected for
- Sexual selection and sperm competition = positive selection, gene expression
related to mating success
Chromosome Regulation
Regulation of genes as a function of chromosome structure examples of how
genomic location, rather than gene function affects regulation
Inversions and sex chromosome strata
Sex chromosomes evolve
when there is linkage of
sex-specific genes and
sex-defining genes
Recombination and then
selection again
Major (X) and minor (Y)
orthologues
XX can initially
recombine freely, but
after inversion they
cannot recombine and
diverge
Recombination halted longest have more divergence
After recombination Y has a massive loss of genes and gene expression
(accumulate missense mutations which silence genes)
Loss of recombination on Y chromosome causes many genes to decay in sequence and
function - only genes that have important roles in male fertility and fitness persist
(Lann and Page, 1999)
How to measure gene regulation
RNA sequencing (RNA-Seq)
1. Isolate mRNA from tissue of interest
2. Sequence all mRNA in sample
3. Count number of sequences mapping to each gene = expression level
Map RNA sequences to underlying genome
What does gene regulation give us?
Permits organismal complexity
- One genome can encode for multiple tissue types: different genes expressed in
different parts of the flower (heat maps show gene expression levels in
different tissues)
- How did flower complexity evolve? Hierarchial clustering. Similarity of 2 tissues
between the species
Eg. carpal tissues similar transcription patterns
- For example 98% of transcriptional output of humans is non-coding: RNAs and
introns serve as regulatory (Mattick, 2001) read!
Changes in gene regulation allow for adaptive evolution
- Gene expression changes underlie some
adaptive traits
- Example: beak size in Darwin’s Finches varies
among species and key to ecological niches
(Mallarino et al., 2011)
High interspecific gene flow, high
morphological diversity entirely due to gene
regulation high BMR = pointier, wedge-like
phenotype
- Organisms adapt to environmental changes through the fixation of mutations
that enhance reproductive success
- E.coli adapts to different growth conditions by fine-tuning protein levels (Babu
and Aravind, 2005) – predicted the cost and benefits of producing LacZ when no
lactose was present in the medium
Grew E. coli in different conditions (low, medium, high concentrations of lactose
over many generations) after ~500 generations, cells evolved state in which they
expressed LacZ at levels predicted by cost-benefit optimisation model
Cells grown in low lactose concentrations ceased lacZ expression by introducing
deletion near promoter
, Medium expressed moderate amounts of enzyme, high = high lacZ mutations
in coding region which altered mRNA/protein stability/modified rate of protein
translation
Mechanisms of transcriptional regulation
Cis-regulation = on same side as Trans-regulation = beyond
Region of DNA that regulates Region of DNA that regulates
expression of genes on the same expression of distant genes:
chromosome, chromosome arm or transcription factors or signalling
neighbourhood genes
Often cis-regulatory elements are Often trans-regulatory elements bind
binding/sites for trans-acting factors to cis-regulatory sites
Enhancers cannot initiate but increases
existing transcription level
Changes in cis recognition sites can
increase/decrease binding affinity of
repressors
Though not all gene expression change is
adaptive
Global patterns of gene expression
Gene expression regulation evolution: as genomes
between chimps and humans are highly similar
phenotypic difference due to regulation
Across 5636 genes, expression divergence across
amniotes roughly clock-like
- Over several species, steady decline in almost all
tissues – not all regulation is adaptive,
decay due to drift testis have the
fastest change (Brawand et al., 2011)
- Suggests most change is due to genetic
drift
Partition genes into different categories
based on variance
- Genetic drift drives force in gene
expression regulation
, - So evolution but most is neutral, with no adaptive strength
- Purifying selection: any variation is deleterious is removed in all cases
- Positive selection (eg. in cerebellum): deleterious mutations are still removed,
but in some species they are selected for
- Sexual selection and sperm competition = positive selection, gene expression
related to mating success
Chromosome Regulation
Regulation of genes as a function of chromosome structure examples of how
genomic location, rather than gene function affects regulation
Inversions and sex chromosome strata
Sex chromosomes evolve
when there is linkage of
sex-specific genes and
sex-defining genes
Recombination and then
selection again
Major (X) and minor (Y)
orthologues
XX can initially
recombine freely, but
after inversion they
cannot recombine and
diverge
Recombination halted longest have more divergence
After recombination Y has a massive loss of genes and gene expression
(accumulate missense mutations which silence genes)
Loss of recombination on Y chromosome causes many genes to decay in sequence and
function - only genes that have important roles in male fertility and fitness persist
(Lann and Page, 1999)
