Lazarus and doppelganger genes - PowerPoint Presentation

Slide1

Lazarus and doppelganger genes

Creation Research Society ConferenceDr. Matthew Cserhati and Bendeguz Levente SzukAnn Arbor, MIJuly 28-30, 2016Slide2

Introduction

There are 1010-1012 different gene familes (Choi, 2006)If an average protein is 267 amino acids (801

bp

) (

Brochieri

, 2005), then there are

4

801

~ 10

160

different possible gene

sequences

Ratio of possible gene sequences

to gene families: 10

160

/10

12

= 10

148Slide3

Introduction

According to François Jacob, no two evolutionary trajectories are the sameMeaning the same species doesn’t evolve twiceThus, in the world of genes, the same gene should also not evolve twiceVery unlikely, since as we saw (Cserhati, 2015, CRS conference), the probability of a random gene sequence being functional is 10-342Slide4

Lazarus speciesSlide5

Lazarus genesSlide6

Examples of Lazarus genes

Gene name

Species distribution

Function

Reference(s)

Lazarus genes

Aristaless

N. vectensis, vertebrates

Homeobox gene, craniofacial development

McGonnell, 2010

Wnt-2,3,4,8,11

N. vectensis, vertebrates

secreted signalling molecules in development

Kusserow, 2005; Miller, 2005DickkopfC. capillata, vertebratescellular differentiation regulatorYang, 2003BMPSuberites (worm), vertebratesDetermination of dorsoventral axis of mesodermMüller, 2003OR genesH. magnipapillata, cephaolocordates, vertebratesOlfaction, cellular migrationChurcher, 2011cytovecN. vectensis, vertebratesIntermediate filemantZimek, 2012Slide7

How many Lazarus genes are there?

Putnam et al. (2007) discovered that there are 13,830 human genes and 12,319 genes from Nematostella vectensis which are present in the eumetazoan

gene set

7,309

present

in

Drosophila

(fruit fly)

7,261 in

Caenorhabditis

elegans

(worm)

This means that around 5,000 (12.3k – 7.3k) genes were lost in the sea anemone and reappeared in humanNematostella vectensis – starlet sea anemoneSlide8

In summary

Some evolutionists may say that genes could have been deactivated throughout long evolutionary time periods and resurfaced later onSurvival as pseudogenesBut why keep a functionless gene for so long?Sequence erosion would occur rapidlySlide9

Doppelganger genes - introductionSlide10

The CaMKII gene

Arabidopsis thaliana

– thale cressSlide11

CaMKII

Average similarity between thale cress, yeast, human, fly, and worm is 54%Boundary for sequence homology is 40%Twilight zone of sequence homologyPlays a role in long-term memory in vertebrates

Obviously plays a role in invertebrates like worms

Also yeast, plants

Obvious question is, why does a protein occur in both plants and

animals with a similar sequence ?Slide12

Other Doppelganger genes

Doppelganger genes

CaMKII

Vertabrates, planarian, yeast, thale cress

neural signal transmission

Mineta, 2003

APX1

Plants, Hydra, trypanosomes

ascorbate peroxidase, plays role in oogenesis

Habetha, 2005

cADPR

Euglena, sponges

ADP-ribosyl cyclase

Puce, 2004Slide13

Other Doppelganger genes

Technau et al. (2007) discovered 56 Nematostella and 44 Acropora* proteins, which are shared uniquely with non-metazoan organisms

plants

, fungi,

protists

, and

prokaryotes

e-score

of <

1e-10

At

an

e-score of 1e-4, 2.7% of

Nematostella and 2.5% of Acropora proteins were shared uniquely with non-metazoans*another anemone speciesSlide14

Horizontal gene transfer and Lazarus/doppelganger genes

Evolutionists could say that Lazarus and doppelganger genes are due to horizontal gene transfer (HGT)Highest proportion of HGT genes are in bdelloid rotifers10% of transcriptsIn more complex organisms HGT is less likelyMore cellular boundaries to pass through

Cell wall, plasma membrane, nuclear membraneSlide15

Horizontal gene transfer and Lazarus/doppelganger

genesHGT between bacteria and eukaryotes would have to introduce introns into the geneNo biological mechanism is known which does thisWhatever foreign gene is found within an organism not caused by HGT may be a Lazarus/doppelganger gene

Whatever gene is not a Lazarus or doppelganger gene could be horizontally transferredSlide16

How many Lazarus/doppelganger genes are there?

Filter 1: N. vectensis genes were BLASTed against sequences from 10 different large taxonomic categoriesh

umans, rodents, mammals, vertebrates, invertebrates, plants, Fungi, Bacteria, Archaea, viruses

e

-score: 1e-20 (strict criterion)

Filter 2: When

BLASTed

against invertebrates

e-score: 1e-4 (lax criterion)

This is to filter out all possible hits with any invertebrate species and to ensure that the gene occurs only in

N.

vect

.

and the other category (gray area in figure)Genes also filtered if they were found in bacteria or viruses which may serve as vectorsSlide17

Animals

=>

Disjunct

groupsSlide18

FilteringSlide19

Taxonomic group

Number of sequences

Number of Nematostella hits (E<1e-20)

Non-invertebrate Nematostella hits (E< 1e-5)

Non-HGT genes (after bacterium+virus double filter)

Vertebrates

17,862

8,220

995

959 (5.4%)

Mammals

19,846

9,128

1,1611,103 (5.6%)Rodents26,33912,1932,0832,002 (7.6%)Human20,20412,3722,1962,117 (10.5%)Invertebrates26,05014,785 [e-score: 1e-4]00Plants39,1774,285325302 (0.8%)Fungi31,5854,447387369 (1.2%)Bacteria332,1932,281411397 (0.1%) [single filter]Archaea19,3579277976 (0.4%) [single filter]Viruses16,6022,4051270 Slide20

Common Lazarus/doppelganger genesSlide21

Lazarus genes in human

The Human Genome Sequencing Consortium discovered 223 genes which were possible HGT genes between bacteria and humansNo similarity to any other nonvertebrate eukaryoteLander et al. (2001) found 113 genes which had no homologs in non-vertebrate eukaryotesThought to be result of HGT but had introns

Salzberg et al. (2001) found only 40 of them to be genuine HGT

Stanhope (2001) found that only 28 of the 113 genes studied by Lander were genuine HGTSlide22

Lazarus genes in human

The data from these study groups was re-analyzed by Crisp et al. (2015) and found 363 genesFrom the 365 genes rejected as HGT by Stanhope, Salzberg and Crisp, 94 genes were rejected as HGT by all groups

Also found

members of 12 gene families with at least 3 genes which were hypothetically transferred from prokaryotes to

humans

Is it possible to transfer a large number of members of a gene family between bacteria and humans by random chance during HGT?Slide23

Note

P-values were calculated by the hypergeometric distribution: p = Hypergeometric(N,M,n,k), where N, the population size is 60,620 human ENSG identifiers present in the Ensembl database, M = the 363 human non-HGT genes found by Crisp et al., n = the size of the gene family under consideration, and

k

= the number of genes from the specific gene family which were found in human.Slide24

HGT genes between bacteria and human with multiple members

Gene family

Number of genes transferred

Number of genes in family

p-value

acyl-CoA synthetase

7

28

2.83e-10

arylsulfatase

3

14

7.38e-5

cytochrome P450, family 26332.17e-7GTPase, IMAP family member6109.38e-12hyaluronan synthase348.61e-7monoamine oxidase441.29e-9Na/glucose (and other solutes) cotransporter 34

8.61e-7

N-acetyltransferase (arylamine N-acetyltransferase)

3

4

8.61e-7

peptidyl arginine deiminase

4

5

6.43e-9

PRAME protein

12

41

1.26e-17

retinol binding protein

3

7

7.4e-6

solute carrier family 37 (glucose-6-phosphate transporter)

5

5

7.7e-12Slide25

Conclusion

The appearance, disappearance, and then subsequent re-appearance of a gene is highly unlikely according to evolution, given the huge size of the gene sequence universeYet Lazarus and doppelganger genes seem to appear abundantly in natureJust like living fossil speciesThere are at least 94 which occur between bacteria and humanUnique or ORFan genes are specific to species, but Lazars/doppelganger genes may also be common

Also a case of mosaicismSlide26

Thanks for your attention!