Genomes and their evolution

How do we study genomes?What can we learn from them?

Why study genomes?• We can look at similarities and differences• We can learn more about gene interaction and control

of gene expression• We can learn more about the history of life on Earth• Genomics: “the study of whole sets of genes and their

interactions within a species, as well as genome comparisons between species”

• Bioinformatics:”The use of computers, software, and mathematical models to process and integrate biological information from large data sets”

• Dependent on technological advances!

How do you sequence a genome? Human Genome Project

• Built on previous technologies

• Linkage map: the order of markers through the chromosomes

• Physical maps: how far apart are the markers?

• Sequencing: break up DNA into pieces and sequence them

Shotgun approach: Venter and Celera

• “Competed” with hierarchical approach

• Competition probably hastened completion of sequencing

• Metagenomics: sequences from organisms within a specified environment

Bioinformatics: you have all that data, what do you do with it?

• Databases and centers• National Center for Biotechnology Information• NCBI houses Genbank– BLAST allows sequences to be compared– Predicted amino acids sequences; comparison to

others– Comparions can be useful for gene identification

• Other centers around the world

What does bioinformatics look like?

ENCODE ushered in the approach of studying DNA- protein interactions

What do we learn bycomparing genomes?

Introns primarilya feature ofeukaryotes, as isnoncoding DNA

What does thismean?

Significance of noncoding DNA?

• Most is repetitive DNA– Transposable elements– Almost half the human

genome

• Unique noncoding; pseudogenes

Transposons

• DNA intermediates• May be excised and

moved, or copied and moved

Retrotransposons• May be origin of reverse

transcriptase• Alu elements• LINE-1 retrotransposons

– LINE: long interspersed nuclear element

– SINE: short…– ERV: endogenous

retroviruses– LTRs: long terminal repeats– May include promoters

and enhancers

STRs: short tandem repeats

• 2 to 5 nuleotides• Actual number of repeats can vary in

individuals• Tends to be at centromeres and telomeres• May have stabilizing effect

(Multi)Gene families

• Collection of two or more related genes

• Identical: to make many copies of an essential protein (like rRNA)

• Non-identical: different versions of a protein

• Developmental significance?

How does genome evolve?• Mutation• Duplication• Alteration of structure– Some regions are

conserved among species

– Might contribute to speciation

– Some sites are more susceptible to mutation than others

How does duplication occur?

A model for evolution of gene families

Exon shuffling: production of novel proteins

• Typically, exon shuffling produces different versions of proteins

• Can lead to formation of new genes

• Transposable elements may be responsible for arrangement of genes on chromosomes

What can be learned by comparing genome sequences?

• When did species diverge?

• What are their common genes?

• Variation within a species• Closely related species:

which regions are stable, which have changed rapidly?– Study genes associated

with species differences

Conservation of developmental genes

• “homeodomain” (regulatory sequence)

• Hox genes contain this region

• Generally associated with development

• Changes can affect body plan

• Regulatory sequences very different in plants

Conservation of developmental genes

• “homeodomain” (regulatory sequence)

• Hox genes contain this region

• Generally associated with development

• Changes can affect body plan

• Regulatory sequences very different in plants

Summary

• Genomics and proteomics are rapidly developing fields

• Bioinformatics allows for the analysis of genomes and proteins in a system-wide approach

• Genomes vary widely among organisms• Eukaryotic genomes are complex and have much

noncoding DNA• Comparing genomes gives insights into evolution

and development