jeremy glasner, ph.d. december 1, 2015. key lessons from microbial evolution microbes have been...

Microbial Evolution

Jeremy Glasner, Ph.D.December 1, 2015

KEY LESSONS FROM MICROBIAL EVOLUTION

Microbes have been evolving for a long time and are extremely diverse

Provide good evidence for natural selection on genome scale

Microbiome data provides evidence of diversity of microbial populations in varying environments

Symbioses between bacteria and hosts evolve commonly

Many modalities exist for transmission of bacterial traits such as pathogenesis and drug resistance

Bacteria are the dominant form of life on the planet

https://en.wikipedia.org/wiki/Biomass_(ecology)

•The timetable• 3.6-3.7 billion years ago: appearance of life• 2.5 billion years ago oxygen-forming photosynthesis• ~2.2 billion years ago: aerobic respiration• ~1.5 billion years ago: first evidence of fossil eukaryotes

The appearance of Life

Fossil evidence of ancient microbes is scant, but suggests very ancient origin, likely ~3.5 billion years ago

"Anything found to be true of E. coli must also be true of elephants.” –Jacques Monod

"Genome Sizes" by Abizar at English Wikipedia. Licensed under CC BY-SA 3.0 via Wikimedia Commons - http://commons.wikimedia.org/wiki/File:Genome_Sizes.png#mediaviewer/File:Genome_Sizes.png

Bacteria now commonly studied by genome sequencing and tend to have small genomes ~1-10 Mb


Variation in Number of Genes Across Tree of Life


Number of genes as a function of Genome Size

WHAT IS AN OME? Genome

Transcriptome

Exome

Methylome

Phenome

Genome-Scale datasets are becoming routinely available from many organisms and even populations and provide incredible insight into the evolution of organisms

MCKINNEY, Emily A. and OLIVEIRA, Marcos T.. Replicating animal mitochondrial DNA. Genet. Mol. Biol. [online]. 2013, vol.36, n.3, pp. 308-315. ISSN 1415-4757.

OUR LITTLE ENDOSYMBIONT GENOME

OUR GENOME(S)

nuclear genome mitochondrial genome microbiome

Most microbes are unculturable

New DNA sequencing-based methods allow us to observe all of the genomes present in a sample without needing to grow a culture

Metagenomics is the popular term for sequencing the genomes from a sample

Often sequence 16S ribosomal RNA genes (highly conserved)

http://www.wagsrevue.com/thewag/?q=content/graphic-science-1

C Huttenhower et al. Nature 486, 207-214 (2012) doi:10.1038/nature11234

Carriage of microbial taxa varies while metabolic pathwaysremain stable within a healthy population.

Key findings from the human microbiome project

Yes, the microbiome can affect behavior

http://phylogenomics.blogspot.com/

Diminished diversity in the human gut microbiome compared to apes

http://u.osu.edu/sabreelab/author/sabree8/

Symbiosis is an “intimate”, “long-term” (evolutionary-relevant time?) interaction between (different types of) organisms encompassing the range from mutualism to parasitism

SYMBIOSIS- MAIN VARIABLES

Route of infection (maternal, horizontal, mixture) Mechanisms of benefiting or exploiting hosts Location of symbionts in host body:

intracellular, between cells, in specialized organ or in other tissues, within gut lumen, etc.

Molecular mechanisms of invading host tissues or cells: similarities and differences between symbionts and pathogens

Escherichia, Salmonella, etc.Xenorhabdus, Photorhabdus, ProteusSoft rotters

Edwardsiella, HafniaYersinia, Serratia, Ewingella

Specialization in plants

Specialization in animals

Plants

Mixed

Animals

Animals

Animals

Animals

Enterobacteria contain many pathogens, as well as many commensals of plants and animals

Mechanisms of bacterial pathogenesis

http://okanogan1.com/wp/wp-content/uploads/2011/02/brinton_conjugation_small.gif

Bacterial Conjugation

Can transfer DNA from donor cell to recipient celle.g. in E. coli a plasmid called “F” for fertility contains genes encoding a structure called a pilus that can transfer the plasmid, and occasionally large pieces of the E. coli chromosome to cells that lack the F plasmid. The transferred DNA can sometimes recombine into the recipient’s genome

So even traditionally “asexually” reproducing organisms do exchange genetic material and undergo recombination, “sex”, but it is often called “lateral gene transfer since it mechanistically somewhat different from sex in most eukaryotes that involves meiosis and recombination

EVOLUTION OF PATHOGENESIS THROUGH HORIZONTAL GENE TRANSFER

Horizontal Gene Transfer (= Lateral Gene Transfer): Transfer of genetic material (DNA) to another organism that is not its offspring.

• Transformation

• Transduction

• Conjugation

Horizontal gene transfer between bacteria was first described in Japan in a 1959 publication that demonstrated the transfer of antibiotic resistance between different species of bacteria

Horizontal Gene Transfer

Consequences:• Phylogenetic relationships are sometimes difficult to discern (as genetic material is being swapped around)

• Rapid transfer of functional genes: pathogenicity genes, rapid evolution of drug resistance

• Bacteria effectively have a HUGE genome size (Pan-Genome), a large genome to draw from, as individual cells can share genes with other individuals

Blattner et al. 1997

1997 – “The” E. coli genome

Extensive variation in gene content

Two E. coli genomes(Perna et al., 2001)

Three E. coli genomes(Welch et al., 2002)

Lineage-specific “islands” can be a

significant fraction (up to

30%) of the genome

Pan-Genome

Core

Variable

Core

Variable

Genome of any one organism Genome of the “species”

The Pan Genome (yellow + blue) of a prokaryotic “species” is much larger than the genome of any one bacterial organism or of the core genome (blue) of the species

Touchon M, Hoede C, Tenaillon O, Barbe V, et al. (2009) Organised Genome Dynamics in the Escherichia coli Species Results in Highly Diverse Adaptive Paths. PLoS Genet 5(1): e1000344. doi:10.1371/journal.pgen.1000344http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000344

E. coli core and pan-genome evolution

http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000344

Evolution of new symbiotic relationships in bacteria can occur by gene acquisitione.g. the evolution of different pathogenic types of E. coli is thought to occur by horizontal (lateral) gene transfer of pathogenicity genes/islands of genes

Example of acquisition of genes encoding type III secretion systems in pathogenic E. coli that can deliver pathogenicity determinants directly into eukaryotic host cells

…it can be hard to determine the environment that matters most in the context of many co-evolutionary events… commensal in one species, pathogenic in another…

http://www.compoundchem.com/wp-content/uploads/2014/09/A-Guide-to-Different-Classes-of-Antibiotics.png

Antibiotics target highly conserved aspects of bacterial growth and metabolism

Antibiotics are often useful for only a subset of bacteria –e.g. evolutionarily/phenotypically related groups

Why do antibiotics kill bacterial cells but not human cells?

Because they target bacterial specific metabolic processes or very specific differences between processes conserved between humans and bacteria

note: chemotherapeutic drugs are hard to develop because…

Antibiotics kill! They are lethal! That is extremely strong selection!

If there are antibiotic resistant variants in the population they will quickly rise to fixation!

Hospitals are evolutionary breeding grounds for selecting for multiple-drug resistant antibiotic strains of bacteria.

Indiscriminant use of antibiotics reduces their long-term utility –e.g. animal agriculture

Evolution of Antibiotics and Antibiotic Resistance

http://www.cmaj.ca/content/180/4/408.figures-only

The evolutionary arms race between antibiotics and antibiotic resistance

For every mechanism of offense there seems to be a good defense…

Antibiotic resistance genes spread among bacteria because they have multiple mechanisms for exchanging DNA (aka Lateral/Horizontal Gene Transfer)

Cyanobacteria

Cyanobacteria

Eukaryote- Plant

Cyanobacteria

Bacteria

Bacteria

Bacteria

Bacteria

Eukaryote-protozoan

Eukaryote-protozoan

Eukaryote-animal

Eukaryote-fungal

(Phylogenetic evidence for gene transfer from organelles)

e.g. Arabidopsis genome has >1000 genes from cyanobacteria

Adapted from slide from Nancy Moran’s Oct 3, 2006 lecture “Symbiotic Bacteria in Animals”

Beneficial microbes in animal hosts--examples

1 Insect-nutritional mutualists (aphids & Buchnera)Many invertebrates have specialized intracellular associations with bacteria that make nutrients

Examples: marine bivalves, leeches, many insects


Metazoa: ancestral loss of many genes underlying biosynthesis of compounds essential for metabolism, including many amino acids and many cofactors. -->dietary requirements.

Little or no gene uptake

Tree of Life, N. Pace


Routes of transmission

Vertical (parent to offspring)

Horizontal May live in the environment (outside hosts), or

not

Mixture of vertical and horizontal Eg acquire from other individuals in the same

family or colony (termites, humans… )

Termite with gut removed

Diverse microbes in termite gut


maternal bacteriocytes containing symbionts

early embryos with symbionts visible

late embryos

J. Sandström

1 mm


1mmJ. White

Buchnera aphidicola within pea aphid bacteriocyte


Aphid eggs containing Buchnera from mother

A. Mira0.5 mm


Shigenobu et al 2000 Nature

The Buchnera gene set (570 genes) is a subset of that of E. coli (~4500 genes)


Essential amino acid biosynthetic pathways

argA argB argC argD argE carAB argF argG argH

Glutamate---> ---> ---> ---> ---> Ornithine ---> ---> ---> ---> ARG

ilvHI ilvC ilvD ilvE

Pyruvate ---> ---> ---> ---> VAL

ilvA ilvHI ilvC ilvD ilvE

Threonine ---> a-Ketobutyrate ---> ---> ---> ---> ILE + Pyruvate

ilvHI ilvC ilvD leuA leuCD leuB ilvE

Pyruvate ---> ---> ---> ---> ---> ---> ---> LEU

aroH aroB aroD aroE aroK aroA aroCPEP+Erythrose ---> ---> ---> ---> ---> ---> ---> Chorismate4-Phosphate

pheA pheA hisC

Chorismate ---> ---> ---> PHE

trpEG trpD trpC trpC trpAB

Chorismate ---> ---> ---> ---> ---> TRP

thrA asd thrA thrB thrC

Aspartate ---> ---> ---> Homoserine ---> ---> THR metB metC metE

Homoserine ---> ---> ---> MET

thrA asd dapA dapB dapD dapC dapE dapF lysA

Aspartate ---> ---> ---> ---> ---> ---> ---> ---> ---> LYS

hisG hisI hisA hisHF hisB hisC hisB hisD

PRPP + ATP ---> ---> ---> ---> ---> ---> ---> ---> HIS

Nonessential amino acid biosynthetic pathways

tyrA tyrA hisC

Chorisimate ---> ---> ---> TYR

proB proA proC

Glutamate ---> ---> ---> PRO

serA serC serB

3-Phosphoglycerate ---> ---> ---> SER

glyA

Serine ---> GLY

cysE cysK

Serine ---> ---> CYS gtBD/gdhA

2-oxoglutarate ---> GLU

glnA

Glutamate ---> GLN

aspC+tyrB

Oxaloacetate ---> ASP

asnB/asnA

Aspartate ---> ASN

alaB/avtA

Pyruvate ---> ALA

GENE / product present in Buchnera GENE / product absent in Buchnera

(based on Shigenobu et al 2000)Adapted from slide from Nancy Moran’s Oct 3, 2006 lecture “Symbiotic Bacteria in Animals”

Moran NA, Bennett GM. The tiniest tiny genomes. Annu Rev Microbiol. 2014;68:195-215. doi: 10.1146/annurev-micro-091213-112901. Epub 2014 Jun 2. PubMed PMID: 24995872.

Tiniest Tiny Genomes

“The extreme case, to date, is the genome of “Candidatus Nasuia deltocephalinicola,” one of two obligate symbionts of the leafhopper Macrosteles quadrilineatus; this Nasuia strain possesses a mere 137 protein-coding genes and a genome of only 112 kb”

evolutionary innovations through symbiosis:

examples

• Eukaryotic cell (mitochondria)• Photosynthesis in eukaryotes

(plastids)• Colonization of land by plants

(mycorrhizae)• Nitrogen fixation by plants (rhizobia)• Animal life at deep sea vents

(chemoautotrophic life systems)• Use of many nutrient-limited niches

by animal lineages


jeremy glasner, ph.d. december 1, 2015. key lessons from microbial evolution microbes have been...

Documents