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Genomes as the Hub
of Biology
UNIT 2
The hub of biology
• As biologists, we seek not only to understand how a single
organism works, but how organisms interact.
• The same is true for genomes.
• To see life clearly, we must understand how genomes relate to
one another.
• Within an individual (cell to cell, developmental changes in gene
expression)
• Within/among populations (variation and change)
• Among species (evolutionary relationships; understanding how
genomes evolve; genome interactions via disease, predation,
etc.)
Genomics and development
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Donut analogy
Monodelphis domestica
Divergence from humans ~180 mya
~18-20k genes
Only eight lack human homologs
The differences between us is primarily due to differences in regulation of the
same suite of genes.
Example = HOX genes – responsible for anterior/posterior patterning in flies,
humans, C. elegans.
Genomics and behavior
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C. elegans dining behavior:
• Wild-type Australian taxa congregate to eat
• British wild-type eat separately
• Traces to a single AA mutation in a transmembrane protein, NPR-1
• http://newswire.rockefeller.edu/2011/05/18/genes-help-worms-decidewhere-to-dine/
Changes in CREB (cyclic AMP response element binding protein) impact learning
and memory in flies and mouse.
Severe, prolonged depression is associated with being homozygous for the short
allele of the serotonin transporter, 5-HTT
Multiple genes are associated with schizophrenia
Genomics and populations
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Phenotypic variation in populations is the raw material of evolution
Genomic variation is the raw material for phenotypic variation
Founder effects and bottlenecks can reduce variation and impact evolutionary
processes in populations
Genomic variation can be measured in multiple ways
Genomics and populations
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SNPs – Single Nucleotide Polymorphisms
• Single base variations among genomes
STRs – Short Tandem Repeats aka microsatellites
Populations with long evolutionary histories tend to have higher variation
• An African origin for humans
• 22 divergent lineages in Africa, three outside of Africa
Genomics and populations
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Mitochondrial haplotypes
Genomics and populations
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SNPs tell a story of
admixture in human
history
Genomics and populations
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SNPs tell the story of admixture in
human history
Comparison of the Neanderthal
and modern human genomes
reveal an influx of novel alleles in
non-African modern humans
Those novel alleles are similar to
Neanderthal alleles
Genomics and populations
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SNPs tell the story of admixture in
human history
Four possible scenarios
• 1 - hybridization between ancient
ancestor and Neanderthals
• 2 – hybridization of ancient
European and Asian populations
with Neanderthals
• 3 – hybridization between
Neanderthals and a common nonAfrican ancestor
• 4 – persistent population
substructure shared between
Neanderthals and modern
humans
Genomics and populations
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SNPs tell the story of population sizes in human history
PSMC (pairwise sequential Markovian coalescent) analysis
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A diploid genome sequence harbors hundreds of thousands of independent loci,
each with its own TMRCA.
Use local densities of heterozygous sites to reconstruct the TMRCA distribution
across the autosomes and chromosome X
Parameters include the scaled mutation rate and recombination rate, and
piecewise constant ancestral population sizes
If you know two, you can estimate the third.
The population sizes inferred
from autosomes of six individuals
~10-60 kya
Severe bottleneck in Eurasian
populations
Less severe in African populations
Genomics and species
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Species are a fundamental unit of evolution
• Despite the fact that no one can truly define what a species is.
Genomics can influence our understanding of species by:
• Providing large scale data sets to determine species relationships
• Buddenbrockia plumatellae
• 129 protein alignments
nematodes
Genomics and species
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Species are a fundamental unit of evolution
• Despite the fact that no one can truly define what a species is.
Genomics can influence our understanding of species by:
• Providing large scale data sets to determine species relationships
• Buddenbrockia plumatellae
• 129 protein alignments
• Quantitative measurements of the divergences between species
• Crocodile vs. alligator whole genome pairwise alignment
• 93.3% identity (assuming G = 20 yrs, TMRCA = 100 my)
• μ(Crocodylia) = ~6.7 x 10 -9
Genomics and species
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Finch beaks
High homozygosity at ALX1 locus in
species with blunt beaks
Transcription factor associated with
cranial morphology
Genomics and species
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Reversing extinctions?
• http://www.livescience.com/40264-how-to-bring-back-the-woollymammoth-infographic.html
Genomics and species
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Bed bugs
Two papers published simultaneously
Genomics and species
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Bed bugs
Two papers published simultaneously
Identified genes related to blood-feeding and
insecticide resistance.
Urban phylogeography
“The two East-West lines of the NYC subway system
showed a similar phylogeographic structure, with
the same split re-occurring in both lines and subsets
of the variants staying within one borough. This
structure suggests that areas of the city in close
proximity to each other show bed bug populations
that are related to each other, and one borough’s
population can be distinct from others.”
Genomics and species
• How big are genomes?