Creation Research Society Conference Dr Matthew Cserhati and Bendeguz Levente Szuk Ann Arbor MI July 2830 2016 Introduction There are 10 10 10 12 different gene familes Choi 2006 ID: 547502
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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!