AAAATTTTCGTATCTGTTGGAGTTAGATAAGCCTACGCTTGATGGACCGTTGGGTGGCTTTCTAAGTGAGCTCGTGCCATCACAATTAATATAAGGAATTGTAGATGTTTCTTTCGTTATAGGTATTTCAA

AATAATTATAAGAACCTACGCCCTCGTCTTTCTCCATTGGAACAGTTGCCGTTTTCGCAGTTCTTTTTGGTTCAGTCCTCATATCATGTGATTCCCCTGGCTCTCCTGATCTTTTTATACTTACTTTGAAAT

CGTCATATGTGTATTTCTTTGATGCAACTCCGATAACGAAGACAATGCTTCCAATAATAACTAAGAATTTGCATACCGTTATTAAACCTACCAAAAGTTTACCTATAAGCTTCTGTAATATTGGCCCCATCA

TTGTTGTGAATACGCACCCTACCAAAAATGATGGGAAATCCAGCACAATACTGCCAGGCCCACTACCTATTGTAATTTTCCATCGTAACCAATCCCTTTTCAAATCCATCCGTGACTTCTATGTCTCGTTA

CTTTCACAGCGTGTGGAGCTACTAGAAAAGTGGCAAAGCTAAACAGCTGATCGAAGTAAACAGAAAAGAACACTAATTGTAGATCAGGCTGTGTACTAGACCTTATTTTACTGTATTTTTTCGGAAAGAA

AAAAGGAGCGCTTTGCAGATCGAAAGTTTCGCTCGTAAATTATTTGTAAGATGCTATTCATAATATGTTAACTGAGAGAAACCAGGTCAAAACAAAACAATTTTGGGCTCTTGCCTCCAAATTTGCCTACC

CTAGAACAGGTATCCATTATCTCGCCTGTACCCGATTAAAAAAAAGACCAATTATTTAAAACTTCTCAAGAAGTTTCATATGCAGTGTATAAGTTGAAGGAATATAGGAATATATATCCTTCAGAAAAGCA

ACACAATACCTAATTACATAACCGATATTTACCTTTTAGAGTGCCTCATTCTTGCAATCTTTCTGTTCGCCATAACACCACCGCCCATGCTCATGCCATTATTTGTTCCCATCCCCATCTGATTAGGGGCT

GACTGCGGCTGCCCAAAAGAAGTTGTCGGCACACCACCTGCCCCCCCAAAAATGGATGATGGATTTGTTACGTTTGAATTGGAACCAGAGGCAGCATTCGCACCAAATATATCACTTGGCCTTAATGC

ATTGGTCGCGGTATTAGTAATTCCGCCATTCAATCCGCTAAAATTAATATTAGGAACTGTTGATGGCGTGAATGAGCTGTTTGTATTGAAAGATGGGGTTTGCGATTGATGTGGTTGGTTATTAGAGCCG

GCAAACACCGTATTAGCATTAGTGTTGCCGTTCATATTAAATACAGAGCCGCCACCAGGCGTTGAATTATTTCCCGTAAAATTAAAAGCAGAGGGAACATTGACATTTTGTGCATTCGTGGAAGGAGGTT

TATTGAATAAACCAGCATTAGCATTAGTTGACGAAGTTGCTGATGTAAAAGGATTGAGACCCCCTGCACCATTGTTTCCAAAATTAAATGAAGATTGATTAGAAGCTGCACCAGTTGCTGCTGTTCCTGA

GCTCGAAAAGCCAAATGCCGAGCCCGCTCCATTCGTATTGCCACTAGCGATACTTTGATCCGGTTTTCCTACGTTAAATGTACCCGCTATATTGGTTCCTGAGGTATTGGAAGTAGTAGTTGTGCCGTT

ACCAGTAGCAGGGGCGTTAAACGAGAATGATGTGGAGTTTGCTGAGGCATTGGTACCATTGGTGTTAGCAGTACCGAATGAAAATGCAGATTTAGATGTTGTATTACCAGTAGCGTCTGTTGGCTTACC

CAAGACAGGAATCGGCGTTGAGGAAGCAGAACCATCGAAGAAAGAAGTTGGAGAGTTTGACTTTTCTTTATTGTGATTGAACTTTGTAAAGGAAAAGCCATTTGATAGCTTCTCCGTATTTGCTGCCGC

TGTACTTGCTGTCGACTTCATCGACTCGGGAGCCCCAAAACTAAAAGATGGTTTTGTGCTAGTGGTTGTTGTATTATTTGTTGTGGAACCGCCAAAGGTGAAAGATGGCGGTGTAGGTCTTTTATCTGT

CTCATTAGCAGGAGGTTTAGTGAAAGAAAATGAGGTGTTAGAGCCTGGTGGTTCTTTAGCTGCATCTGACTTACCAAATGAAAACAATGGCTTTGGTTGTGAGGTTTTTGAAGACGCAAACGTAAAGGA

GGGCTTTTTAGGTTCCGAAACAACAGATGAATCTTTTTGAGCAGGTTCAGTAAAAGAAAAAGTTGGCTTGAGAGTCTTATCATCCGTCGGTGCTTGAACATCAACAGGCTTGCCCGGAAACGAAAACGA

GGGTTTAGCTGCTTCGTTTGAAATTGGACTACTCTTACGTTCCTCCTCTGACTTAGAGAAAGAGAATGTAGGTTTCGCACTTCCCTCAGAGATCTTATTTTCACTTGTTGACTGCCCAAAAGTAAAAGTAG

GCTTCTTGACTATTGTGGCAGGTGTCTCAGATGGTTTGGTGTGTGTTTCTTTCGCGGTGGCGGCTTTACCAAAGGTAAATTGTGCAGAGGAGTCAATATTGCTTGTTACATCAGCTTTTTTTCCGAATGT

AAATAATGGTGTACCTTCAGCTTGCTTATCACTTGCACCAAAGACAAAGCTTGGTTTCCCTGATGCGTCCTTTTCTGACTCTCCCTTTTTGGTCTCCTTTTGATCACCGGTCTTGCCGAAATCGAATAAAG

GCTTGGTGTTTGTATCCTCGCTAACAGGTAAACGCCTTTTTCTTTTGGGCTCATTTTCATCATCACCTTCATCACCATTCTCTTCTTGTTTACCAAAAGAAAATATTGGAGCAGTTGATTTTGGAGGCGCG

TCTGATTCTGTATGATTTTCACTTTTTTCGGATGTCTTTCCAAATTTAAAAGGTTGACTGGCAGAAGTAACGGTATCTGATTTACCACCAAAATTGAATAAAGTTGTGGAAGGGACAGTATTGTCGACAGC

CTTAGTTTTATTAGCCTTTTGGCTAAAATTGAATGATAAGGTAGGCGCCTCGGCAGTTTTCGTTGACTTATCGGTTTTTCCCATTTCTACACTCGATTTAAAGACTGCACCTGCAGAAGAAGTTGCCTTAG

GAGAAGTTTTCTTAGATGGAGTCTCATTGTCCTTGATAAAGTCAAAACCTACGGTGGGCAAAACAATACTTTCTTTGTCCTTTTTGGGCTCAATATTTTTCTTTAACGTAGGCGTACCAGAGCGCTCTGAA

TTGGGAACAAAGCTCTCCTGAATAGGGGCAGTTTTTGCAACTGTGGAAGCTGGTCCTTTTAAAAGTAGATTTTTTTGAGGATTCGATAACCTATTAGAGTTGATGTCTGCACGTAGGTCTTCAATTTCGC

TTGTCAGGTTAGGGCCTGTAGCCAGATTGCCATTTGAAATACTACTCTTAATATTATTTCTATTCTCGCTTGTCTTCTGATCACCGCCAGCGTTACCTTCCTTATCCTTGTTATCCTTTTTTTGTATAGCGT

CATATTCTGACAAATCATATTCAAAATTTGCTGACCACACGGTCCCCTTTGACTGACTATGAAACCTTTTTCTATTGGATCTATTTTTCAATGATTTGAGAATGGGTAGTCCAACATTGGTGTCTTCACCGC

TTTTTCCGGCCAACTGCCTAGTGCAAGAACCGTTTTTAATAGGGGAAGGAGTAGATGATGTGCATAGGTACGATCCTCCCTCATCGCTTTTACTTTGAGAGCCCAATATAACCGACGATGTAATAGATG

GAAATTCAGTTGATTGAATTAATCCAAGCTCACGCATATTTCTCACCCTCTGCTTCTCCCTTAATAACCTCAGTCTTTGAATGGGCAAAATTGGCAAAAGCGGCGGTCTCTCAGTGTTTTCGGTTCCATAT

ATTATAATTGGCGCATTATTGTTGTTCTGAGTTAAGCTGTCGCTATGCTGTGATGTACCGGACACCCTCTTTCTCTTATTAACATGCAGTGTGTCTTCAACATCTGATTCCTCCAAATGATTCGCGTATGA

GAGGTTTGAACTGAAAACTTTCTTGCTCGATGGCCGTTTTTTATTGGGGTTTGTGAAGAATGATTTTAAAGTGGAAGAAAACGATCTCTTTTCGACACGTGGAGAAGACATCACAGAAGAAGTGTTTGAA

GACATGAATGACTAAAAATTGTCGCTCACTCTCTGTCCCTATAACCCTTTCGAGGCTAATATCCTATCGTATTTGCACCGCTACGTAGTGTCCTTATTGAGTTCCTCATCACTTATTTTCTTTAAGTGTTTC

TTGACATTACGAAATTTCGTCAAAGAAAAAAATTAAAATGAAAAAGCATTTCAATGTCACATAATACGAACCATTGATCACGTGCAACGACAAACCCTAAATATAAAAACTAGGGCGTAAAAACCGGGGC

TTGAAAATTAGGGCATAAAATAGGCTTTGCATACACGTGACTTATATTTGGTGTCGGCGTTTTCTTTACGCGGTGTAGTGTAAATCTCTTGTCGTACAAGTGGATATACGCACTGTATACCTCCAGTAACA

CCAAAAAAAAAACCGTGGTTGTCCCATGTAAACGAGTACCGCACACGTAGGCCAAAGCACTCCAGAGAGACTTCGTGTCAAAGGTCTATAATAGGTGGTGCCTTCTTGCTTCTTTTTTGCAGATTCTTA

GTATAATACGCTAGACTATTGTACTTTCTAATTTTAAGAGATATCTTTTTCCTCACAAAGATTTCGTTAAGCAATCGAAGTAAAGTACTCCATCAGAAGAGTTTTTAAAATTTTCGTATCTGTTGGAGTTAGA

TAAGCCTACGCTTGATGGACCGTTGGGTGGCTTTCTAAGTGAGCTCGTGCCATCACAATTAATATAAGGAATTGTAGATGTTTCTTTCGTTATAGGTATTTCAAAATAATTATAAGAACCTACGCCCTCGT

CTTTCTCCATTGGAACAGTTGCCGTTTTCGCAGTTCTTTTTGGTTCAGTCCTCATATCATGTGATTCCCCTGGCTCTCCTGATCTTTTTATACTTACTTTGAAATCGTCATATGTGTATTTCTTTGATGCAAC

TCCGATAACGAAGACAATGCTTCCAATAATAACTAAGAATTTGCATACCGTTATTAAACCTACCAAAAGTTTACCTATAAGCTTCTGTAATATTGGCCCCATCATTGTTGTGAATACGCACCCTACCAAAA

ATGATGGGAAATCCAGCACAATACTGCCAGGCCCACTACCTATTGTAATTTTCCATCGTAACCAATCCCTTTTCAAATCCATCCGTGACTTCTATGTCTCGTTACTTTCACAGCGTGTGGAGCTACTAGA

AAAGTGGCAAAGCTAAACAGCTGATCGAAGTAAACAGAAAAGAACACTAATTGTAGATCAGGCTGTGTACTAGACCTTATTTTACTGTATTTTTTCGGAAAGAAAAAAGGAGCGCTTTGCAGATCGAAAG

TTTCGCTCGTAAATTATTTGTAAGATGCTATTCATAATATGTTAACTGAGAGAAACCAGGTCAAAACAAAACAATTTTGGGCTCTTGCCTCCAAATTTGCCTACCCTAGAACAGGTATCCATTATCTCGCC

TGTACCCGATTAAAAAAAAGACCAATTATTTAAAACTTCTCAAGAAGTTTCATATGCAGTGTATAAGTTGAAGGAATATAGGAATATATATCCTTCAGAAAAGCAACACAATACCTAATTACATAACCGATA

TTTACCTTTTAGAGTGCCTCATTCTTGCAATCTTTCTGTTCGCCATAACACCACCGCCCATGCTCATGCCATTATTTGTTCCCATCCCCATCTGATTAGGGGCTGACTGCGGCTGCCCAAAAGAAGTTGT

CGGCACACCACCTGCCCCCCCAAAAATGGATGATGGATTTGTTACGTTTGAATTGGAACCAGAGGCAGCATTCGCACCAAATATATCACTTGGCCTTAATGCATTGGTCGCGGTATTAGTAATTCCGCC

ATTCAATCCGCTAAAATTAATATTAGGAACTGTTGATGGCGTGAATGAGCTGTTTGTATTGAAAGATGGGGTTTGCGATTGATGTGGTTGGTTATTAGAGCCGGCAAACACCGTATTAGCATTAGTGTTG

CCGTTCATATTAAATACAGAGCCGCCACCAGGCGTTGAATTATTTCCCGTAAAATTAAAAGCAGAGGGAACATTGACATTTTGTGCATTCGTGGAAGGAGGTTTATTGAATAAACCAGCATTAGCATTAG

TTGACGAAGTTGCTGATGTAAAAGGATTGAGACCCCCTGCACCATTGTTTCCAAAATTAAATGAAGATTGATTAGAAGCTGCACCAGTTGCTGCTGTTCCTGAGCTCGAAAAGCCAAATGCCGAGCCCG

CTCCATTCGTATTGCCACTAGCGATACTTTGATCCGGTTTTCCTACGTTAAATGTACCCGCTATATTGGTTCCTGAGGTATTGGAAGTAGTAGTTGTGCCGTTACCAGTAGCAGGGGCGTTAAACGAGAA

TGATGTGGAGTTTGCTGAGGCATTGGTACCATTGGTGTTAGCAGTACCGAATGAAAATGCAGATTTAGATGTTGTATTACCAGTAGCGTCTGTTGGCTTACCCAAGACAGGAATCGGCGTTGAGGAAG

CAGAACCATCGAAGAAAGAAGTTGGAGAGTTTGACTTTTCTTTATTGTGATTGAACTTTGTAAAGGAAAAGCCATTTGATAGCTTCTCCGTATTTGCTGCCGCTGTACTTGCTGTCGACTTCATCGACTC

GGGAGCCCCAAAACTAAAAGATGGTTTTGTGCTAGTGGTTGTTGTATTATTTGTTGTGGAACCGCCAAAGGTGAAAGATGGCGGTGTAGGTCTTTTATCTGTCTCATTAGCAGGAGGTTTAGTGAAAGA

AAATGAGGTGTTAGAGCCTGGTGGTTCTTTAGCTGCATCTGACTTACCAAATGAAAACAATGGCTTTGGTTGTGAGGTTTTTGAAGACGCAAACGTAAAGGAGGGCTTTTTAGGTTCCGAAACAACAGA

TGAATCTTTTTGAGCAGGTTCAGTAAAAGAAAAAGTTGGCTTGAGAGTCTTATCATCCGTCGGTGCTTGAACATCAACAGGCTTGCCCGGAAACGAAAACGAGGGTTTAGCTGCTTCGTTTGAAATTGG

ACTACTCTTACGTTCCTCCTCTGACTTAGAGAAAGAGAATGTAGGTTTCGCACTTCCCTCAGAGATCTTATTTTCACTTGTTGACTGCCCAAAAGTAAAAGTAGGCTTCTTGACTATTGTGGCAGGTGTCT

CAGATGGTTTGGTGTGTGTTTCTTTCGCGGTGGCGGCTTTACCAAAGGTAAATTGTGCAGAGGAGTCAATATTGCTTGTTACATCAGCTTTTTTTCCGAATGTAAATAATGGTGTACCTTCAGCTTGCTTA

TGGTCTCCTTTTG CTTGCCGAAATCGAATAAAG

GTGTTTGTATCCTCGCTAACAGGTAA CGCCTTTTTCTTTTGGGCTCATTTTCATCA

CACCTTCATCACCATTCTCTTCTTGTTTAGGC AAAAGAAAATATTGGAGCAGTTGATTTTGGA

AGGGCGCGTCTGATTCTGTATGATTTTCACG GTTTTTTCGGATGCTCTTTCCAAATTTAAA

GGTTGACTGGCAAGAAGTAACGGTATC TACCACCTTAAAAATTGAATAAAGT

GGGACAGAATTGTCG

TGGTCTCCTTTTG CTTGCCGAAATCGAATAAAG

GTGTTTGTATCCTCGCTAACAGGTAA CGCCTTTTTCTTTTGGGCTCATTTTCATCA

CACCTTCATCACCATTCTCTTCTTGTTTAGGC AAAAGAAAATATTGGAGCAGTTGATTTTGGA

AGGGCGCGTCTGATTCTGTATGATTTTCACG GTTTTTTCGGATGCTCTTTCCAAATTTAAA

GGTTGACTGGCAAGAAGTAACGGTATC TACCACCTTAAAAATTGAATAAAGT

GGGACAGAATTGTCG

ATGGCTTTGG GGTTTTTGAAGAC

ACGTAAAGGAGGTTT AGGTTCCGAAACAA

GAGCAGGTTCAG AAGTTGGCTG

ATGGCTTTGG GGTTTTTGAAGAC

ACGTAAAGGAGGTTT AGGTTCCGAAACAA

GAGCAGGTTCAG AAGTTGGCTG

Bernard Dujon Bernard Dujon

Déclin et contingence, bases de l'évolution

biologique

Decline and contingency, bases of biological

evolution

Déclin et contingence, bases de l'évolution

biologique

Decline and contingency, bases of biological

evolution

Colloque Sciences de la vie, sciences de l'information Centre culturel international de Cerisy-la-Salle, 17-24 Septembre 2016

Ernst Haeckel, 1834 -1919

Unicellular

(without nuclei)

Unicellular

(with nuclei) Pluricellular

1866

2016 Multiple

Reversible

Symbioses

Gregor Johann Mendel, 1822 - 1884

1866

Genotype Phenotype

DNA RNA Proteins 1953 RNA RNA

2016 Gene and allele

interactions Complex RNA

interactions (splicing, editing, processing, RNAi, trans-generational …)

Intrinsic variance

Regular selection acting on limited variations

Charles Robert Darwin

(1809 -1882)

Abrupt genetic changes

Hugo Marie de Vries

(1848 -1935)

?

Species or

individual n° 2

Common core of genes

(ancestral origin)

Species or

individual n° 1

Species or

individual n° 3

Restricted set of genes

(origin ?)

ca. 100 genes mutated and

a few genes missing

CNV in the human genome CNV in the human genome

Yoon et al., (2009)

Genome Res. 19: 1586-1592

Segmental duplications Segmental deletions

Gene losses

Pseudogenes

Deletions

Gene gains

Duplications

Fission / fusion

De novo formation

Horizontal acquisitions

Each genome is only a snapshot in time within

continual changes, not an optimized structure

1: Genomes are (much) too big

2: There are too many genes in genomes

The C-value paradox (Swift, 1950)

Major lessons from genomics Major lessons from genomics

Genomes are too big Genomes are too big

Paramecium

tetraurelia

100 Mb

Gonyaulax

grindleyi

98 000 Mb

1000 X

Zea mais

3 000 Mb

Vitis vinifera

487 Mb

Fritillaria

assyriaca

100 000 Mb

1000 X

Amoeba dubia

670 000 Mb

Homo sapiens

2 900 Mb

Necturus lewisi

100 000 Mb

Saccharomyces

cerevisiae 12 Mb

55 000 X

Genome sizes and content

Coding exons (exome) 1.9 % of genome

Introns

> 100 000

Other

pseudo -genes

~25 000

Regulations and

evolution: 98.1 %

Mobile elements > 1 100 000

Genes are complex mosaics (exons and introns)

Many genes encode RNA, not proteins

Genomes contain many other elements than genes:

- pseudogenes and traces of ancient sequences

- mobile elements and their remnants

- NUMTs, NUPTs, NUPAVs

- structural elements of chromosomes (CEN, TEL)

- transcription is pervasive

UTR and introns Coding exons Mobile elements and remants Pseudogenes DNA RNA

Too many genes in genomes

The genome of Saccharomyces cerevisiae

13.4 Mb (> 70 % coding) ~ 5 800 protein-coding genes

44 % of genes are not unique (paralogs)

Many genes escaped systematic genetic screenings

1996

No genome is minimal

In each genome many genes are dispensible

< 18 % of genes are essential for cellular life

> 50 % of the non-essential genes generate no detectable phenotype when deleted

The yeast systematic gene deletion collection The yeast systematic gene deletion collection

Core and pan-genomes Core and pan-genomes Variability + dispensability --> core- and pan-genomes

Medini et al., 2005 «The microbial

pan-genome» Curr. Op. Genetics & Development 15: 589-594

Closed species: e.g. B. anthracis

Open species: e.g. S. agalactiae

> What is a species ?

From 61 E. coli genomes fully sequenced (Lukjancenko et al., 2010 Microb. Ecol. 60: 708-720)

ca. 4 000 genes / individual genome

pan-genome : 15 574 gene families

core-genome: 993 gene families

Adapted from Wolf and Koonin (2013) Bioessays 35: 829-837

Phase of complexification: brief, sporadic

Phase of reductive evolution: long, nearly clockwise

Burst of novel

lineages

Gradual reductive

evolution in each

lineage

Reductive evolution

Parasitism, commensalism, symbiosis: Microsporidia, Chlorarachniophytes, Cryptophytes

Loss of genes and loss of functions play the key role in evolution

Role of sex, loss of sex and horizontal acquisitions: Bdelloid rotifers

Free-living eukaryotes: Yeasts

Microsporidia Microsporidia

Corradi and Slamovits, 2010,

Brief. Funct. Genomics 10: 115-124.

2001 vol. 414: . 450-453

Genome size: 2.5 Mb

Total genes: 1 997

Microsporidia Microsporidia

Horizontal gene acquisitions in

Encephalitozoon hellem Horizontal acquisition of genes involved in nucleic-acid metabolism

Alexander et al. 2016 PNAS 113: 4116-4121

Complex ancestor Intermediate forms Small number of genes

Large genomes

Final forms Small number of genes

Small genomes

Gene loss

Intron loss

Genome size

reduction

Horizontal

acquistions

Gould, 2012, Nature 492: 46-48

Bigellowiella natans Ancestral rhizaria

Guillardia theta Ancestral chromalveolate

Primary endosymbiosis Secondary endosymbiosis

Ancestral eukaryote

Secondary endosymbiosis Secondary endosymbiosis

Viridiplantae

Unikonts Chromalveolata

Excavata

2 313 84

8

748 5 666

Rhizaria

Keeling et al., 2005 Trends in Ecology and Evolution, 20: 670-676

Genomics of the eukaryotes Genomics of the eukaryotes

Bigelowiella natans

Guillardia theta

Curtis et al. (2012) Nature 492: 59-65

Genome size (Mb) 87.2 94.7

Split CDS (%) 80 86

Mean exons /gene 6.4 8.8

Mean intron size (nuc.) 110 184

Nucleomorph:

3 chromosomes:

196, 181, 174 kb

inverted repeats at

chromosome ends (rDNA, ubiquitin-

conjugating enzyme gene)

Douglas et al., 2001 Nature

410: 1091-1096

Nucleomorph:

3 chromosomes:

141, 134, 98 kb

inverted repeats at

chromosome ends (rDNA, DnaK

pseudogenes)

Gilson et al., 2006 PNAS

103: 9566-9571

Secondary endosymbiosis Secondary endosymbiosis

Example of a genomic quartet of 4

scaffolds

pairs of

ohnologs

alleles of one

ohnolog

Nature (2013) 503: 453-457

Total genome size 244 Mb (including 26 Mb homozygous 2x)

49,300 protein-coding genes

Numerous homologous blocks (colinear regions) forming two groups: - pairs of ohnologs (mean 74 % identity) corresponding to an ancient

genome duplicaton - pairs of alleles (mean 96 % identity) for each member of the pair of

ohnologs. Their coexistence in the same genome forms quartets that, altogether, cover 40 % of the entire genome (---> a locally tetraploid genome)

Asexual metazoa Asexual metazoa World-wide expansion

Survive total desiccation >

genome fragmentation and

regeneration

Asexual reproduction

The genomic structure is incompatible with conventional meiosis

Allelic pairs are found on the same chromosomes

Colinear regions do not extend to entire chromosome scale

Multiple traces of gene conversion between gene copies reassort alleles without meiosis

Multiple traces of horizontal gene acquisition of non-metazoan origin throughout the genome (8%)

Asexual metazoa Asexual metazoa

M M

M M

M M

B B

B B

B B

etc… etc… etc… etc…

M M B B B B M M

etc…

M M B B

B B M M

etc… etc… etc…

What are yeasts ? What are yeasts ?

Generation 0: 1 cell

Generation 1: 2 cells

Generation 2: 4 cells

Generation 3: 8 cells

Generation 100: ~1030 cells (approx. one week of growth)

i.e. ~ 10 trillions of tons = a several centimeters-high crust covering all world continents

Unicellular forms of modern fungi (devoid of fruiting bodies) adapted to rapid and

unlimited clonal proliferation so long as nutrients are available.

Generation 10: 1 024 cells

Generation 20: 1 048 576 cells

Generation 30: ~109 cells

Generation 50: ~1015 cells

Exponential

mitotic growth

Natural yeasts and experimental models Natural yeasts and experimental models

Terrestrial habitats Leaves, roots, trunks

fruits, plant exudates,

insect guts, soils

Saccharomyces, Lachancea,

Naumovozyma, Kluyveromyces,

Kazachstania, Eremothecium,

Schizosaccharomyces …

Aquatic habitats Fresh or saline water,

planctonic or surfaces

of plants and animals

Rhodotorula, Sporobolomyces,

Debaryomyces, Metchnikowia,

Leucosporidium …

Human, animal or plant pathogens or commensals Antagonist effect against various plant diseases Saccharomyces, Candida, Dipodascus, Cryptococcus, Malassezia

Taphrina, Protomyces, Eremothecium, Galactomyces …

Fermentable sugars: fructose, glucose, sucrose, maltose, melibiose, raffinose, lactose …

Oxidative utilization of a very large variety of organic compounds, including: Non-fermentable sugars: xylose, arabinose, ribose, rhamnose, fucose … Non-fermentable alcohols: methanol, ethanol, propanol,

glycerol, erythritol, ribitol, arabitol, mannitol … Amino-sugars: glucosamine, acetyl-glucosamine, galactosamine… Organic acids: lactic,

succinic, citric, malic … Other compounds: acetone, ethyl acetate, glucuronic acid, anthracene …

Need organic Nitrogen (but some species are able to assimilate nitrate or nitrite)

> 1 500 species

The world of yeasts The world of yeasts

flagellated cells

loss of flagellum

Numerous species e.g. Saccharomyces Debaryomyces, Yarrowia

Few species e.g. Schizosaccharomyces

Ascomycota

~ 1000 MYr

Basidiomycota Some species e.g. Rhodotorula

Some species e.g. Cryptococcus

Few species e.g. Malassezia

Recurrent formation of other yeasts

Rare species e.g. Hortea

Approximate number of generations from present

106 108 109 1010 1011 107 1012

human-chimpanzee separation

"Budding yeasts"

"Fission yeasts"

Filamentous fungi

with fruting bodies

Fungi with fruting

bodies

Fungi with fruting

bodies

Fungi with fruting

bodies

«modern» fungi Dikarya

~1500 MYr

~1100 MYr

Microsporidia and «primitive» fungi

Chytridiomycota Glomeromycota Zygomycota Neocallimastigomycota Blastocladiomycota

Origin of Taphrinomycotina

Origin of Saccharomycotina

Yeasts

M M

Mycelium of Ascomycota or Basidiomycota

M M

M M

B B

B B

B B

etc…

~ Linear

growth

mitosis

~ Exponential

growth

etc… etc… etc…

M M B B B B M M

etc…

M M B B

B B M M

etc… etc… etc…

WhatWhat are are yeastsyeasts ?? WhatWhat are are yeastsyeasts ??

Yeast genomes are highly evolved structures that have lost a number of

ancestral features.

Contrary to common intuitive thinking, yeasts are not a homogeneous

group of closely related, evolutionary primitive eukaryotes. They have

emerged recurrently from distinct lineages of more complex fungi.

Saccharomycotina genome signatures Saccharomycotina genome signatures

Ogataea polymorpha Dekkera bruxellensis

Komagataella pastoris Lindnera jadinii (Candida utilis)

Ogataea parapolymorpha Kuraishia capsulata

Methylo

trophs

Saccharomyces uvarum

Candida dubliniensis

Blastobotrys adeninivorans

Yarrowia lipolytica

Nadsonia fulvescens

Eremothecium cymbalariae

Kazachstania exigua Kazachstania servazzii

Lachancea thermotolerans

Lachancea kluyveri

Kluyveromyces lactis

Saccharomyces cerevisiae

Nakaseomyces (Candida) glabrata

Saccharomyces paradoxus Saccharomyces mikatae Saccharomyces kudriavzevii

Naumovozyma castellii

Lachancea waltii

Eremothecium gossypii

Vanderwaltozyma polyspora

Kazachstania africana

Naumovozyma dairenensis

Tetrapisispora phaffi

Sac

char

omyc

etac

eae

Clavispora lusitaniae

Millerozyma sorbitophila

Candida albicans

Meyerozyma guilliermondii

Candida parapsilosis

Candida tropicalis

Scheffersomyces stipitis

Lodderomyces elongisporus Candida orthopsilosis

Spathaspora passalidarum

«C

TG

»

Debaryomyces hansenii

basal

lineages

Zygosaccharomyces rouxii Torulaspora delbruckii

Nakaseomyces bacillisporus

ZT clade

KLE clade

WGD

code

Geotrichum candidum

Gene numbers

4 700 –

6 000

6 100 –

6 400

5 000 –

6 000

6 100 –

6 800

Genome size

9 -

14

12 -

14

12 -

14

12 -

24

Mb

Coding capacity

> 70

> 70

> 70

~ 45

%

Split genes

3 - 5

6 - 7

15

15 -

35

%

Loss of HP1-mediated chromatin modification & Loss of canonical RNAi machinery

Debaryomyces hansenii

Yarrowia lipolytica

Saccharomyces cerevisiae

1115

329

1443

2823

369 85

834

Gene losses Deletions

Pseudogenes

Gene gains Duplications & sub- or neo-functionalization Hybridizations Horizontal acquisitions De novo formation

functional losses associated to gene loss

Sugar utilization GAL7 (UDP transferase), GAL10 (epimerase), GAL1 (kinase), GAL3 (activator), SUC2 (invertase)

Phosphate metabolism PHO3, PHO5, PHO11, PHO12 (acid phosphatases), PHO89 (transporter)

Nicotinic acid biosynthesis BNA1, BNA2 (dioxygenases), BNA4 (monooxygenase), BNA5 (kynureninase), BNA6 (phosphoribosyl transferase), BNA7 (kynurenin formamidase)

Allantoine metabolism DAL1, DAL2 (allantoinases), DAL3 (ureidoglycolate lyase)

Transporters OPT1, OPT2 (oligopeptide-transporters)

Etc …

functional gains associated to gene loss

General

metabolism Nicotinic acid NAD+

External nicotinic acid

permeases

Synthetic enzymes

In C. glabrata, the intracellular concentration of NAD+ depends directly on the external concentration of nicotinic acid

---> regulate specific adhesion to epitheliums (Domergue et al., 2005 Science 308, 866-870)

Eukaryotic-type centrom

eres

Post WGD

ZT clade

CTG

Methylotrophs

Basal

KLE clade

Taphrinomycotina

Poin

t centro

mere

s

Sa

cc

ha

rom

yc

eta

cea

e

> 10 kb

3 A A A A 3 3 3

IR IR

3 3 3 A A 3 3 3

heterochromatin heterochromatin

Point centromeres Point centromeres 3

A

Canonical histone H3

Centromeric histone H3 variant (CenP-A)

3 A 3 3 3 3 3

0.13 kb

CDE I CDE II CDE III Recruitment of plasmid elements

Malik and Henikoff, 2009 Cell 138: 1067-1082

Regio

nal c

entro

mere

s

3

3 – 5 kb

A A A A A 3 3 3 3 3

LTR and Ty remnants IR IR

Loss of classical heterochromatin

modification

Geotrichum candidum

24.8 Mb, 6 804 CDS, 35 % with intron(s).

SpecificallySpecifically RetainedRetained Ancestral Ancestral GenesGenes (SRAG)(SRAG)

Debaryomyces hansenii 113 SRAGs (2.0 %) Amino-acid, carbon metabolism, transport … Geotrichum candidum 263 SRAGs (3.9 %) Transcriptional regulation, cell cycle, cellusose /pectin hydrolysis

… Yarrowia lipolytica 232 SRAGs (3.6 %) Extracellular proteases, oxydo-reduction …

Saccharo mycotina

Pezizo mycotina

Taphrinomycotina

Basidiomycota

Pseudo-orphans with discordant phylogenies

280 genes have no homolog in any sequenced Saccharomcotina, but have homologs in Pezizomycotina and / or Basidomycota 17 correspond to horizontal transfers from filamentous fungi (low sequence divergence with outgroup) 263 correspond to SRAG (same sequence divergence with outgroup as other genes)

X

X

Gene loss

and decay

Evolved form 1

Evolved form 2

Evolved form 3

Etc … Duplications, sub-functionalization, neo-

functionalization, exon-shuffling

accompanied by selection

----- adaptations

Complex ancestor etc…

Novel lineage

Novel lineage

Horizontal gene acquistions

Introgressions

Hybridizations, endosymbiosis

Genome duplication

Exon-shuffling

De novo gene formation

--- major innovations

SummarySummary

Genomes are never minimal

Evolution is mostly reticulate