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.)

• 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 development

• 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-decide-

where-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 behavior

• 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

• 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

• Mitochondrial haplotypes

Genomics and populations

• SNPs tell a story of admixture in human history

Genomics and populations

• 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

• 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 non-African ancestor

• 4 – persistent population substructure shared between Neanderthals and modern humans

Genomics and populations

• SNPs tell the story of population sizes in human history• PSMC (pairwise sequential Markovian coalescent) analysis

• 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.

Genomics and populations

The population sizes inferred from autosomes of six individuals

~10-60 kyaSevere bottleneck in Eurasian populationsLess severe in African populations

• 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

Genomics and species

nematodes

• 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

• Finch beaks• High homozygosity at ALX1 locus in

species with blunt beaks• Transcription factor associated with

cranial morphology

Genomics and species

• Reversing extinctions?• http://www.livescience.com/40264-how-to-bring-back-the-woolly-

mammoth-infographic.html

Genomics and species

• Bed bugs• Two papers published simultaneously

Genomics and species

• 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?

Genomics and species