Marsupial phyloSNPs

Introduction to Marsupial phyloSNPs

In this project, new genomic data from the Tasmanian devil (Sarcophilus harrisii), Tasmanian tiger (Thylacinus cynocephalus), and echidna (Tachyglossus aculeatus) are analyzed for significant changes at the protein coding level. The goal is to find single amino acid changes in one of these species at a highly invariant residue in a well-conserved exon in a gene with known or predictable tertiary structure. Such changes are thought to enrich for genetic changes with significant, adaptive biochemical or phenotypic consequences (1,2,3,4), in contrast to ordinary SNPs at positions of low conservation. Thus phyloSNPs are informative to the distinctive biology of the species carrying them and suggest a focus for subsequent experiment.

Marsupial genomic and cDNA data to date has been quite limited compared to placental mammal. Yet as outgroup, metatheran animals provide important context to placentals and represent important context in understanding human protein evolution. The monotheres are inevitably limited by the paucity of extant species (basically platypus and echidna) and dim prospects for fossil DNA. Consequently echidna provides an important adjunct to the existing but incomplete platypus assembly. While extant birds and reptiles -- the preceding divergence node -- are abundant it must be remembered that a very considerable time elapsed (from 310 mry to 175 mry) prior to divergence of mammals with living representatives. This gap of 135 myr is comparable to the whole evolutionary record of theran mammals.

Assumed vertebrate phylogenetic tree

Marsupial relationships taken from 2009 paper establishing the mitochondrial genome sequence of the Tasmanian tiger (Thylacinus cynocephalus):

Newick tree that generates vertebrate phylogenetic tree used in the analysis here:

((((((((((((((((((homSap,panTro),gorGor),ponPyg),macMul),calJac),tarSyr),(micMur,otoGar)),tupBel),
(((((musMus,ratNor),dipOrd),cavPor),speTri),(oryCun,ochPri))),
(((((vicPac,susScr),turTru),bosTau),((equCab,(felCat,canFam)),(myoLuc,pteVam))),(eriEur,sorAra))),
(((loxAfr,proCap),echTel),(dasNov,choHof))),
(monDom,((macEug,triVul),(sarHar,thyCyn)))),
(ornAna,tacAcu)),
((galGal,taeGut),anoCar)),
xenTro),
(((tetNig,takRub),(gasAcu,oryLap)),danRer)),
calMil),
petMar);

Phylo-sorting data

-	-	-	-	-	-	-	((((((((((((((((((	-	-	-	-
10	26	10	>	27	gene	homSap	,	Homo	sapiens	(human)	hg181
11	38	11	>	40	gene	panTro	),	Pan	troglodytes	(chimp)	panTro
12	25	12	>	26	gene	gorGor	),	Gorilla	gorilla	(gorilla)	gorGor
13	40	13	>	42	gene	ponPyg	),	Pongo	pygmaeus	(orang)	ponAbe
14	28	14	>	30	gene	macMul	),	Macaca	mulatta	(rhesus)	rheMac
15	12	15	>	12	gene	calJac	),	Callithrix	jacchus	(marmoset)	calJac
16	48	16	>	53	gene	tarSyr	),(	Tarsius	syrichta	(tarsier)	tarSyr
17	29	17	>	31	gene	micMur	,	Microcebus	murinus	(mouse_lemur)	micMur
18	37	18	>	39	gene	otoGar	)),	Otolemur	garnettii	(bushbaby)	otoGar
19	50	19	>	57	gene	tupBel	),(((((	Tupaia	belangeri	(tree_shrew)	tupBel
20	31	20	>	33	gene	musMus	,	Mus	musculus	(mouse)	mm91
21	43	21	>	45	gene	ratNor	),	Rattus	norvegicus	(rat)	rn41
22	18	22	>	19	gene	dipOrd	),	Dipodomys	ordii	(kangaroo_rat)	dipOrd
23	14	23	>	15	gene	cavPor	),	Cavia	porcellus	(guinea_pig)	cavPor
24	45	24	>	48	gene	speTri	),(	Spermophilus	tridecemlineatus	(squirrel)	speTri
25	35	25	>	37	gene	oryCun	,	Oryctolagus	cuniculus	(rabbit)	oryCun
26	33	26	>	35	gene	ochPri	))),(((((	Ochotona	princeps	(pika)	ochPri
27	52	27	>	59	gene	vicPac	,	Vicugna	pacos	(lama)	vicPac
54	57	28	>	49	gene	susScr	),	Sus	scrofa	(pig)	
28	51	29	>	58	gene	turTru	),	Tursiops	truncatus	(dolphin)	turTru
29	11	30	>	11	gene	bosTau	),((	Bos	taurus	(cow)	bosTau
30	20	31	>	21	gene	equCab	,(	Equus	caballus	(horse)	equCab
31	22	32	>	23	gene	felCat	,	Felis	catus	(cat)	felCat
32	13	33	>	14	gene	canFam	)),(	Canis	familiaris	(dog)	canFam
33	32	34	>	34	gene	myoLuc	,	Myotis	lucifugus	(microbat)	myoLuc
34	42	35	>	44	gene	pteVam	))),(	Pteropus	vampyrus	(macrobat)	pteVam
35	21	36	>	22	gene	eriEur	,	Erinaceus	europaeus	(hedgehog)	eriEur
36	44	37	>	47	gene	sorAra	))),(((	Sorex	araneus	(shrew)	sorAra
37	27	38	>	28	gene	loxAfr	,	Loxodonta	africana	(elephant)	loxAfr
38	41	39	>	43	gene	proCap	),	Procavia	capensis	(hyrax)	proCap
39	19	40	>	20	gene	echTel	),(	Echinops	telfairi	(tenrec)	echTel
40	17	41	>	18	gene	dasNov	,	Dasypus	novemcinctus	(armadillo)	dasNov
41	15	42	>	16	gene	choHof	))),(	Choloepus	hoffmanni	(sloth)	choHof
42	30	43	>	32	gene	monDom	,((	Monodelphis	domestica	(opossum)	monDom
55	55	44	>	29	gene	macEug	,	Macropus	eugenii	(wallaby)	
56	56	45	>	46	gene	sarHar	),(	Sarcophilus	harrisii	(tasmanian_devil)	
57	60	46	>	56	gene	triVul	,	Trichosurus	vulpecula	(bushytail_possum)	
58	59	47	>	55	gene	thyCyn	)))),(	Thylacinus	cynocephalus	(tasmanian_tiger)	
43	34	48	>	36	gene	ornAna	,	Ornithorhynchus	anatinus	(platypus)	ornAna
59	58	49	>	50	gene	tacAcu	)),((	Tachyglossus	aculeatus	(echidna)	
44	23	50	>	24	gene	galGal	,	Gallus	gallus	(chicken)	galGal
45	46	51	>	51	gene	taeGut	),	Taeniopygia	guttata	(finch)	taeGut
46	10	52	>	10	gene	anoCar	)),	Anolis	carolinensis	(lizard)	anoCar
47	53	53	>	60	gene	xenTro	),(((	Xenopus	tropicalis	(frog)	xenTro
48	49	54	>	54	gene	tetNig	,	Tetraodon	nigroviridis	(pufferfish)	tetNig
49	47	55	>	52	gene	takRub	),(	Takifugu	rubripes	(fugu)	fr21
50	24	56	>	25	gene	gasAcu	,	Gasterosteus	aculeatus	(stickleback)	gasAcu
51	36	57	>	38	gene	oryLap	)),	Oryzias	latipes	(medaka)	oryLat
52	16	58	>	17	gene	danRer	)),	Danio	rerio	(zebrafish)	danRer
60	54	59	>	13	gene	calMil	),	Callorhinchus	milii	(elephantfish)	
53	39	60	>	41	gene	petMar	)	Petromyzon	marinus	(lamprey)	petMar
											
44	44	51	f	51	gene	fasta	tree_syntax	genus	species	common	ucsc
phy	alp	phy		alp

Candidate analysis

(methods explained here shortly)

Case of ERN2

Here a very ancient L appears to be transitioning to F at marsupial node but has not settled down so ends up L or F depending on lineage-sorting on each terminal marsupial leaf whereas placentals have settled on the phenylalanine (a phyloSNP caught in mid-air). While L and F might seem about the 'same' as amino acids, the branch length conservation totals say both are important but for different reasons: this is not a waffle codon or reduced alphabet situation.

ERN2 endoplasmic reticulum to nucleus signalling 2
remote hoverall homology to ERN1 yet for this exon, only 3 diffs so some possibilities for confusion

ERN1_monDom       KLPFTIPELVQASPCRSSDGILYM all ERN1s are leucine

uc002dma.2_hg18_5 KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_panTro KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_ponAbe KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_rheMac KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_calJac KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_tarSyr KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_micMur KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_tupBel KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_mm9_5_ KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_rn4_5_ KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_cavPor KLPFTIPELVHTSPCRSSDGVFYT
uc002dma.2_speTri KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_oryCun KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_ochPri KLPFSIPELVHASPCRSSDGVFYT
uc002dma.2_turTru RLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_bosTau RLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_equCab KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_felCat RLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_canFam KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_myoLuc KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_eriEur KLPFTVPELVHTSPCRSSDGVFYT
uc002dma.2_sorAra KLPFTIPELVHASPCRSSDGVFYT
uc002dma.2_loxAfr KLPFTIPELVHAS-----------
uc002dma.2_proCap ---------------------FYT
uc002dma.2_echTel KLPFTIPELVLASPCRSSDGVFYT
uc002dma.2_dasNov KLPFTIPELVHTSPCRSSDGIFYT
uc002dma.2_monDom KLPFTIPELVHASPCRSSDGVLYT
macropus eugeneii KLPFTIPELVQASPCRSSDGILYM
uc002dma.2_ornAna KLPFTIPELVQSSPCRSSDGILYT
uc002dma.2_anoCar KLPFTIPELVQSSPCRSSDGIIYT
finch             KLPFTIPELVQSSPCRSSDGVLYT
chicken           KLPFTIPELVQASPCRSSDGILYM
XenopusT          KLPFTIPELVQSSPCRSSDGILYT
XenopusL          KLPFTIPELVQSSPCRSSDGILYT
uc002dma.2_tetNig KLPFTIPELVQASPCRSSDGVLYM
uc002dma.2_fr2_5_ KLPFTIPELVQASPCRSSDGVLYM
uc002dma.2_gasAcu KLPFTIPDLVQSAPCRSSDGILYT
uc002dma.2_oryLat KLPFTIPELVQSAPCRSSDGILYT
uc002dma.2_petMar KLPFTIPELVHASPCRTSDGVLYT

ERN1 are all L
uc002jdz.2_hg18_5 KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_panTro KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_ponAbe KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_rheMac KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_calJac KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_tarSyr KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_micMur KLPFTIPELVQASPCRSTDGILYM
uc002jdz.2_otoGar KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_tupBel KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_mm9_5_ KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_rn4_5_ KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_dipOrd KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_cavPor KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_speTri KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_oryCun KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_vicPac KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_turTru KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_bosTau KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_equCab KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_canFam KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_myoLuc KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_pteVam KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_eriEur KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_sorAra KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_loxAfr KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_proCap KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_echTel KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_dasNov KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_choHof KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_monDom KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_ornAna KLPFTIPELVHASPCRSSDGILYM
uc002jdz.2_galGal KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_taeGut KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_anoCar KLPFTIPELVQASPCRSSDGILYM
uc002jdz.2_xenTro KLPFTIPELVQSSPCRSSDGILYT
uc002jdz.2_tetNig KLPFTIPELVQASPCRSSDGVLYM
uc002jdz.2_fr2_5_ KLPFTIPELVQASPCRSSDGVLYM
uc002jdz.2_gasAcu KLPFTIPELVQASPCRSSDGVLYM
uc002jdz.2_oryLat KLPFTIPELVQASPCRSSDGVLYM
uc002jdz.2_danRer KLPFTIPELVQASPCRSSDGILYM

Case of XXXX

(more shortly)

Case of YYYY

(more shortly)

Case of ZZZZ

(more shortly)