Gene Family Evolution: Horizontal Gene Transferdurand/Phylogenetics/2011/Lectures/Lecture11.pdf3 (a) NEW: acquisition of a new gene missing in other members of a given clade, 1. Loss

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Gene Family Evolution:

Horizontal Gene Transfer

03‐327/727 Lecture 11

Also referred to as lateral transfer

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Horizontal gene transfer (HGT)Why do we care?

1. Best way to identify HGT: disagreement between gene tree and species tree

Species tree

A B C

A B C

Gene tree

2. Unrecognized HGT can confound species tree inference

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Horizontal gene transfer (HGT)Why do we care?

• Genetic diversity

• Adaption to changing environment

• Purge deleterious mutations

• More efficient selection of beneficial mutations.

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1. Alternative to sex

Species tree

A B C


• How to detect HGT

• HGT in Bacteria

• HGT in Eukaryotes

– Barriers to HGT in Eukaryotes

– Plastids

– Case studies

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(a) NEW: acquisition of a new gene missing in other members of a given clade, 1. Loss and regain2. Non‐orthologous gene transfer

(b) ADDITIONAL: acquisition of a paralog of the given gene with a distinct evolutionary ancestry, and

(c) REPLACEMENT: acquisition of a phylogenetically distant ortholog followed by xenologous gene displacement, that is, elimination of the ancestral gene

Classification of horizontal transfer events

Koonin et al. ARM (2001) 55 709‐42

Detecting Horizontal Transfers

Unexpected phylogenetic tree topology

• Unusual phyletic pattern

• Conservation of gene order

• Anomalous DNA composition

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Fish Mouse HumanChicken

Tim

e

A A1A2 A1 A1A2

Contemporary Sequences

HA1MA1 HA2FA CA


Terminology review….

HA1MA1 HA2FA CA

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Orthologs: characters that have descended from a common ancestral character via speciation.

HA1MA1 HA2FA CA


HA1MA1 HA2FA CA

Paralogs: characters that have descended from a common ancestral character via Duplication.

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HA1MA1 HA2FA CA

Xenologs: characters that have descended from a common ancestral character via horizontal transfer

Mn‐dependent transcriptional regulator

Unexpected phylogenetic tree topology

(Tatusov, 1996)

eubacteriaarchaea

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uuremgenmpneubsubbhalctracpneutpalbbur

Species Tree

The signature of horizontal transfer isincongruence between the species tree and the gene tree

Horizontal transfer event

Gene Tree

uurempneu

bsubbhalctracpneu

tpalbbur

mgen

Phylogenetic tree for glutamine synthetase indicates horizontal transfer between the three domains.

BacteriaArchaeaEukaryote

• Species of archaea and bacteria are mixed and, therefore, are not monophyletic.

• The eukaryotes are monophyletic however, the Bacteria, and not the Archaea, is its closest outgroup.

• Several bacterial species have both a bacterial GSI isoform and a eukaryoticGSII isoform.

Brown, J.B. (2003) NRG 4 121‐132

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Problems for detectionRuling out other sources of tree disagreement

• Tree construction artifacts:

– Rate heterogeneity: Different rates of substitution at different sites

– “Heterotachy”: Changes in rate over time

– “Fast clock species”: One species is change much faster than the others

• Duplication followed by differential loss

• Transfer of genes between nucleus, mitochondrion, chloroplast, etc.



Origin of gene Gene loss

Horizontal transfer OR Lineage‐specific gene loss

Here, horizontal transfer is the most parsimonious explanation because only one transfer event needs to be hypothesized while two gene loss events need to be assumed in the gene loss model.

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• Independent origin? – (for SNPs, fusion events)• Gene loss?• Horizontal transfer?

Unusual phyletic pattern

Conservation of gene order

Gene order is not generally conserved in microbial genomes

E. coli

B. subtilis

V. cholerae

• The presence of three or more genes in the same order in distant genomes is extremely unlikely unless these genes form an operon.

• Each operon typically emerges only once during evolution and is maintained by selection ever after.

• Therefore, when an operon is present in only a few distantly related genomes, horizontal gene transfer seems to be the most likely scenario.

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Genes with conserved gene order tend to be functionally related

Huynen et.al, Curr. Opin. Struct. Biol. June 2000

Tryptophan biosynthesis operon across genomes

Species have characteristic codon usage

Anomalous DNA composition

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Analysis of codon usage of B. subtilis genes reveals three classes of genes

Class 3 (13%) genes that were apparently horizontally transferred.

Class 1 comprises the majority of the B. subtilisgenes (82%)

Class 2 (5%) genes that are highly expressed under exponential growth conditions

Because some of the genes in this group showed clear relationships with bacteriophage genes, thehypothesis has been proposed that all these genes were alien and have been acquired horizontallyfrom various sources.

Kunst, F et al. Nature (1997) 390 249‐256

• Amelioration – the process in which a sequence adjusts to the base composition and codon usage of the resident genome

• Amelioration is a function of the relative rate of G,C to A,T mutations

• Due to amelioration, very ancient horizontal transfer events would not be detected by using the method anomalous DNA composition.

Lawrence and Ochman. J Mol Evol (1997) 44:383–397

Amelioration

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• HGT in Bacteria



– Plastids

– Case studies


• Mechanisms


• HGT in Bacteria



– Plastids

– Case studies

Classical view

• Occasionally

• Never

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• Mechanisms


• HGT in Bacteria



– Plastids

– Case studies

Emerging view

• Rampant

• More and more examples are coming to light

1) Transformation – prokaryotes can take up free DNA from their surroundings

2) Conjugation – (bacterial sex) an organism builds a tube‐like structure known as the pilus, joins it to its ‘‘mate’’, and transfers a plasmid through the tube.

3) Transduction – genes can be moved from one prokaryote species to another via viruses.

Mechanisms of horizontal transfer(also referred to as lateral transfer)

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Horizontal transfer by transformationCommunity of cellsof species B

Community of cells of species A

DNA from aLysed cell

A cell picks up the DNA and incorporates into genome

‘mutation’ rises to fixation in the species B

1.

2.

3.

mutation fixation

Transfers can be either selectively driven orselectively neutral.

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Koch’s Postulates

• The microorganism must be found in abundance in all organisms suffering from the disease, but should not be found in healthy organisms.

• The microorganism must be isolated from a diseased organism and grown in pure culture.

• The cultured microorganism should cause disease when introduced into a healthy organism.

• The microorganism must be reisolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent.

Robert Koch, 1843–1910

Classical Microbiology

Implications of Koch’s postulates:

• One pathogen = one disease

• The pathogen always causes disease

• Bacterial infections are caused by a “monoclonal” population

– All individuals have identical genomes

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In the 1950’s, it was recognized that resistance to multiple antibiotics could be trans‐ferred from Shigella to E. coli in a single event.

HGT is a rare event, e.g., • Antibiotic resistance• Virulence factors

Mid‐20th Century View

Genomic view of microbiology

• Bacterial infections are diverse, polyclonal populations.

• Pathogenicity is contextual; virulence depends on

– particular combination of genes in individual genomes,

– the genetic profile (gene complement) of the bacterial

population

– host environment.

• Genetic exchange via horizontal gene transfer, resulting in

new combinations of genes and alleles that modulate

virulence, evasion of host defense systems, and drug

resistance is a fundamental aspect of the infectious process,

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.Pangenome (Supragenome): The complete set of all gene clusters in a species.

Core Clusters: Gene clusters shared by ALL strains in a species.

Distributed Clusters: Gene clusters NOT present in all strains.

A recent study of 44 Streptococcus pneumoniae genomes:

Microbial Pan‐Genome

Genes per strain 2107Genes in pangenome 3221Core 1666 (52%)Distributed 1555 (48%)

Donati et al.,

Models to Study the PangenomeFinite Supragenome Model (Justin Hogg)

Core genes as a function of sequenced genomes.

Predicted core size: 1647 genes.

New genes as a function of sequenced genomes.

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Andam & Gogarten, Nature Reviews Microbiology 9, 543‐555 (July 2011)

Horizontal transfer and prokaryotic speciation



• HGT in Bacteria



– Plastids

– Case studies

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Barriers to transfer in (multicellular) eukaryotes

• Propensity for DNA uptake varies greatly

• Genomic DNA enclosed in nucleus

• Differential intron processing

• Segregation of reproductive cell lines

Dunning Hotopp, TIG, 2011

Horizontal transfer involving animals

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Bock, Trends Plant Scince, 2009

Horizontal transfer involving plants

Richards, Current Biol. 2011

Horizontal transfer within fungi

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Acquisition of plastids through endosymbiosis

Keeling

Dunning Hotopp, TIG, 2011

An HGT model of the accumulation in the nucleus of genes originating in an organelle or endosymbiont

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The unorthodox lifestyle of bdelloid rotifers

Can survive

• Total dessication

• Ionizing radiation

• No sex

How?

. Gladyshev et al (2008)., Science ,

320 (5880) 1210 ‐ 1213

Massive Horizontal Gene Transfer in Bdelloid Rotifers

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Horizontal transfer of photosynthetic genes in sea slugs

Rumpho M E et al. PNAS 2008;105:17867-17871

©2008 by National Academy of Sciences

Agrobacterium: A plant pathogen that transforms its host

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Passage of T‐DNA from Agrobacterium into host plant nuclear DNA

Documents

Gene Family Evolution: Horizontal Gene Transferdurand/Phylogenetics/2011/Lectures/Lecture11.pdf3 (a) NEW: acquisition of a new gene missing in other members of a given clade, 1. Loss