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.

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Presentation transcript:

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 where-to-dine/ Changes in CREB (cyclic AMP response element binding protein) impact learning and memory in flies and mouse. Multiple genes are associated with schizophrenia Severe, prolonged depression is associated with being homozygous for the short allele of the serotonin transporter, 5-HTT 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 kya Severe bottleneck in Eurasian populations Less 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 Genomics and species

Reversing extinctions? mammoth-infographic.html Genomics and species

How big are genomes? Genomics and species