Immunoglobulins, MHC and T Cell receptors genes in ......2020/10/24 · Immunoglobulins, MHC and T Cell receptors genes in Cetaceans Francisco Gambon-Deza´ Servicio Gallego de Salud

Immunoglobulins, MHC and T Cell receptors genes in Cetaceans

Francisco Gambon-DezaServicio Gallego de Salud (SERGAS), Unidad de Inmunologıa, Hospital do Meixoeiro, 36210

Vigo, [email protected]

Abstract

Cetaceans correspond to mammals that have returned to the marine environment. Adaptive changesare very significant with the conversion of the limbs into flippers. It is studied the changes thathave occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant re-gions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgDgene, which is composed of three CH domains but CH1 similar to CH1 of immunoglobulin M. Inthe IGHV locus, it exist a decrease in the number of VH genes with the absence of genes withinClan I. The number of Vλ genes is greater than that of Vκ. In the genes for T lymphocyte recep-tors, it exists a decrease in the number of Vα genes with loss of significant clades and subclades.In Vβ and Vγ, there is also the loss of clades. These declines of Vα, Vβ and Vγ are not presentArtiodactyla, and they are specific to Cetaceans. In MHC present tree evolutive lines of class Igenes. These species have DQ, DR, DO and DM genes, but they are no present DP genes.

Keywords: Cetaceans immunoglobulins, Evolution of Immunoglobulins, MHC Cetaceans, TCRcetaceans.

1. Introduction

Cetaceans are mammals that returned to the aquatic environment. The closest terrestrial mam-mals are the Artiodactyla, more specifically the hippopotamus. In their adaptation process, grossphenotypic changes have occurred with the conversion of limbs to flippers and flukes. There aretwo parvordens. One is the Odontoceti (Cetaceans with teeth like the dolphin) and another calledMysticeti that encompasses the whales with a feeding system through filtering. Fossils of whaleancestors dating back 50 million years (Gatesy & O’Leary, 2001). In molecular studies, the diver-gence of the species present today began 35 million years ago (?).

The organs of the immune system have been studied in detail, finding no differences with ter-restrial mammals. These studies strengthen the idea of the conservation of immune structures inmammals despite morphological and environmental changes in their evolution (Romano et al.,2002). However, this environmental change must impact the immune system. The presenceof antibodies in serum was studied, and its messenger RNA sequenced (Nash & Mach, 1971;Andresdottir et al., 1987). An IgM sequence of RNAm is described in dolphin. This immunoglob-ulin in the transmembrane region shows a variation in the CART motif of uncertain significance(Lundqvist et al., 2002). In dolphins, two genes for IgG are described with characteristics similar

.CC-BY 4.0 International licenseperpetuity. It is made available under apreprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in

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https://doi.org/10.1101/2020.10.24.353342

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4.0

Physeter_catodon

Eschrichtius_robustus

Pontoporia_blainvillei

Balaenoptera_musculus

Mesoplodon_bidens

Tursiops_truncatus

Lagenorhynchus_obliquidens

Balaenoptera_acutorostrata

Monodon_monoceros

Lipotes_vexillifer

Phocoena_phocoena

Inia_geoffrensis

Globicephala_melas

Sousa_chinensis

Tursiops_aduncus

Megaptera_novaeangliae

Phocoena_sinus

Orcinus_orca

Kogia_breviceps

Eubalaena_japonica

9,91

25,42

33,04

26,34

18,87

33,5

25,9

24,72

18,39

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33,5

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15,36

14,29

15,37

Delphinidae

Odontoceti

Physeteridae

Iniidae

Pontoporiidae

Lipotidae

Phocoenidae

Monodontidae

Mysticeti

Figure 1: The figure represents the phylogenetic tree of the species present in this study. It has been obtained from theweb http://www.timetree.org/. In the nodes, the divergence time is expressed.

to those of other mammals (Mancia et al., 2006). The sequence of an mRNA for IgA has also beenpublished (Mancia et al., 2007) having similarity to the IgA of artiodactyls.

Of the genes of the T lymphocyte receptors, there is a study of the TRAV/DV and TRGV loci.They found a simple gene structure with few V genes in its loci (Linguiti et al., 2016). There is arecent study of the gene structure of MHC class II genes in cetaceans, concluding that they presenta general pattern similar to that of other mammals (Zhang et al., 2019). There are also studieson the allelic variability of these proteins. Alleles are common in class I and DQB antigens.The presence of the same alleles in different species is interesting, suggesting a positive selection(Hayashi et al., 2003; Xu et al., 2009; Vassilakos et al., 2009).

In mammals, the number of V regions in the immunoglobulin and TCRs loci is variable(Olivieri et al., 2014b). There is currently no explanation for this variation. In that work, a lownumber of V genes evidenced in mammals that have evolved to adapt to an aquatic environment.Cetaceans are the most significant. In this work, it describes the characteristics of the genes of



https://doi.org/10.1101/2020.10.24.353342


antibodies, V genes of TCRs and MHC of cetaceans.

2. Material and Methods

The entire study is with freely available data. The sequences of the genomes are in the NCBI,and on the web, https://vgp.github.io/. To obtain the sequences of interest, we use our applica-tions developed in Python. For the general study of the sequences, the Biopython library wasused (Cock et al., 2009). The exons of the constant regions of the heavy and light chains of theantibodies and the MHC class I and class II genes were performed with a machine learning (ten-sorflow (Abadi et al., 2016)) trained for their recognition. Other publications express the specificoperation (Olivieri et al., 2020b). Vgeneextractor program similar to the previous one adapted forrecognition of the V exons was used (Olivieri et al., 2020a). These applications extract the possi-ble target exon. For this, a blast was performed with an artificial sequence that gives positivity tothe objective. All hypothetical possible exons around the hit are translated into amino acids. Theamino acid sequences are analyzed by machine learning, and the target sequences are obtained.Later, after a manual review, if the exons obtained are considered valid, they are added to machinelearning.

The graphic representation of the exons was also done with a simple python application usingthe genomediagram library (Pritchard et al., 2006).

The amino acid sequences obtained were aligned with the MAFFT program (Katoh et al.,2005). The trees were built with the Fasttree program (Price et al., 2010) using the LG matrix(Le & Gascuel, 2008) and gamma parameter. The tree visualization was done with the Figtreeprogram (http://tree.bio.ed.ac.uk/software/figtree/)

3. Results

Cetaceans are Laurasatheria mammals that have adapted to the marine environment. These an-imals have undergone significant phenotypic changes. We decided to study the essential moleculesof the adaptive immune system.

At the time of writing this article, there are 12 reference genomes deposited with the NCBI.With computer tools (CHfinder) we look for the exons that code for CHs of immunoglobulins.

3.1. immunoglobulinsAll species have at least one gene for each of the immunoglobulin classes present in mammals

(table 1), Gene duplication found for IgG. All cetaceans have IgD with three exons for CHs. Itstands out that the CH1 of IgD is identified to the CH1 of IgM while CH2 and CH3 are as IgD.

The study of 8 genomes is represented schematically in the figure 2. In general, all species havea very conserved position of genes with an IgM followed by an IgD, two genes for two isotypesof IgG, one gene for IgE and a gene for IgA. An exception is that of Balaenoptera acutorostrata,which has a gene for internal IgG in a standard position and three genes for 3 IgGs appear aftergen for IgA. Also in Physeter catodon, additional exons of IgGs appear, but they must be part ofpseudogenes.



http://tree.bio.ed.ac.uk/software/figtree/

https://doi.org/10.1101/2020.10.24.353342


Table 1: Number of genes for Immunoglobulins class

IGHM IGHD IGHG IGHE IGHA IGKC IGLCMonodon monoceros 1 1 1 2 1 1 1Neophocaena asiaeorientalis 1 1 2 1 1 1 1Phocoena sinus 1 1 2 1 1 1 2Tursiops truncatus 1 1 2 1 2 1 3Orcinus orca 1 1 2 1 1 1 1Physeter catodon 1 1 2 1 1 1 3Balaenoptera acutorostrata 1 1 4 1 1 1 1Balaenoptera musculus 1 1 2 1 1 1 1Lagenorhynchus obliquidens 1 1 1 1 1 1 1Globicephala melas 1 1 1 ? ? 1 1Lipotes vexillifer 1 1 1 1 1 1 2Sousa chinensis 1 1 2 1 1 1 1

The same CHfinder program has added training to identify the exons of the constant regionsof the light chains of immunoglobulins. All species have one gene for the constant region of thekappa chain and 1 to 3 genes for the lambda chain (table 1).

3.2. V regionsAmong the genes of immunoglobulins and those of T lymphocyte receptors, the genes that

show the greatest changes in number enter species correspond to the V genes. We obtained the Vexons of the seven loci that exist in mammals. The V exons obtained with the Vgeneextractor areexpressed in Table 3 As can be seen, Cetaceans present a low number of V exons in all loci. Alsohighlights the presence of a greater number of Vλ than Vκ genes.

In previous publications in which the Immunoglobulin sequences in the dolphin were de-scribed, they indicated the possibility of a low number of VH genes (Lundqvist et al., 2002).With all the VH sequences obtained from the exons in the germinal line of the cetacean species,we made a phylogenetic tree. Additionally we add the consensus sequences of the three clans thatare represented in primates and the sequences of the VH present in the cow.

The distribution of the clades indicates the presence of particularities in the sequences (figure3). There are sequences belonging to Clan III, and there are no sequences associated with Clan I.There is a high heterogeneity between sequences close to Clan II. The presence of an additionalclade with a large number of sequences not associated with the three known Clans stands out. Inthis clade are the 21 VH exons of the cow. Within this new clade, the program extracted sequencesthat present an additional conserved segment of more of 30 amino acids with abundant prolinesand cysteines amino acids. These sequences have already been described in the cow (Deiss et al.,2019). Here we find that the same process of conformation of long CDR3 must occur in cetaceans.

Cetaceans for light chains have a higher number of Vλ genes than Vκ. Three Vκ clans andat least 5 Vλ clans have been described. the primate sequences were aligned with those obtained



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exon3_A-0.999

exon2_A-0.989

exon1_A-0.926

exon3_E-0.995

exon3_E-0.948

exon2_E-0.99

exon1_E-0.943

exon3_G-0.956

exon2_G-1.0

exon1_G-0.998

exon1_G-0.998

exon1_G-0.999

exon2_G-1.0

exon2_G-0.419

exon3_G-0.967

exon2_G-0.988

exon1_G-0.999

exon3_D-0.949

exon1_M-0.941

exon4_M-0.386

exon3_M-0.923

exon2_M-0.981

exon1_M-0.963

NC_041224.1NC_041224.1NC_041224.1NC_041224.1NC_041224.1

exon3_A-1.0

exon2_A-0.781

exon1_A-0.977

exon4_E-0.982

exon3_E-0.995

exon2_E-0.988

exon1_E-0.998

exon3_G-0.892

exon2_G-1.0

exon1_G-0.999

exon2_G-1.0

exon2_G-1.0

exon1_G-0.999

exon3_D-1.0

exon2_D-0.991

exon1_M-0.609

exon4_M-1.0

exon2_M-0.696

exon1_M-0.943

NW_004438415.1NW_004438415.1NW_004438415.1NW_004438415.1NW_004438415.1

exon3_A-1.0

exon2_A-0971

exon1_A

exon4_E-1.0

exon3_E-0.902

exon2_E-0.996

exon1_E-0.992

exon3_G-0.913

exon2_G-1.0

exon1_G-0.999

exon3_G-0.942

exon2_G-1.0

exon1_G-0.999

exon1_M-0.948

exon4_M-0.1

exon3_M-0.673

exon2_M-0.971

exon1_M-0.986

exon3_G-0.987

exon2_G-1.0

exon1_G-1.0

exon3_A-1.0

exon2_A-0.957

exon1_A-1.0

exon4_E-0.895

exon3_E-1.0

exon2_E-0.989

exon1_E-0.999

exon3_G-0.987

exon2_G-1.0

exon1_G-0.999

exon1_G-1.0

exon3_D-1.0

exon2_D-0.981

exon2_D

exon4_M-1.0

exon3_M-0.436

exon3_M-338

exon2_M-0.673

exon1_M-0.892

NW_006726265.1NW_006726265.1NW_006726265.1NW_006726265.1NW_006726265.1 gap

Balaenoptera acutorostrata

exon1_G-1.0

exon2_G-1.0

exon3_G-0.994

exon1_G-1.0

exon2_G-1.0

exon3_G-0.987

NW_006731512.1

exon3_D-0.999

exon2_D-0.988

Super_scaffold_11Super_scaffold_11Super_scaffold_11Super_scaffold_11

Balaenoptera musculus

φ? φ?

Physeter catodon

exon1_M-0.991

exon2_M-0.906

exon3_M-0.442

exon4_M-1.0

exon1_M-0.985

exon2_D-0.987

exon3_D-1.0

NW_006783775.1 NW_006783775.1

exon1_G-1.0

exon2_G-1.0

exon3_G-0.967

exon1_E-0.998

exon2_E-0.979

exon3_E-0.999

exon4_E-0.948

exon1_A-1.0

exon2_A-0.538

exon3_A-1.0

NW_006778806.1 NW_006778806.1

Lipotes vexillifer

exon3_A-1.0

exon2_A

exon1_A-1.0

exon4_E-0.975

exon3_E-0.998

exon2_E-0.963

exon1_E-0.999

exon2_G-1.0

exon2_G-0.998

exon1_G-0.998

exon2_G-1.0

exon2_G-0.999

exon1_G-0.999

exon3_D-1.0

exon2_D-0.994

exon1_M-0.954

exon4_M-1.0

exon3_M-0.477

exon2_M-0.89

exon1_M-0.952

NC_045764.1NC_045764.1NC_045764.1NC_045764.1NC_045764.1

Phocoena sinus

exon1_M-0.979

exon2_M-0.926

exon3_M-0.442

exon4_M-1.0

exon1_M-0.626

exon2_D-0.994

exon3_D-1.0

exon1_G-0.999

exon2_G-1.0

exon3_G-0.901

exon1_G-0.999

exon2_G-1.0

exon3_G-0.908

exon1_E-0.998

exon2_E-0.984

exon3_E-0.995

exon4_E-0.977

exon1_A-1.0

exon2_A-0.79

exon3_A-1.0

NC_047035.1 NC_047035.1 NC_047035.1 NC_047035.1 NC_047035.1

Tursiops_truncatus

Orcinus orca

exon3_A-1.0

exon2_A-0.712

exon1_A-0.859

exon4_E-0.951

exon3_E-0.999

exon2_E-0.989

exon1_E-0.995

exon3_G-0.74

exon2_G-1.0

exon1_G-0.999

exon3_G-0.844

exon2_G-1.0

exon1_G-0.999

exon3_D-1.0

exon2_D-0.994

exon1_M-0.905

exon4_M-1.0

exon3_M-0.999

exon2_M-0.911

exon1_M-0.678

QWLN02014001.1QWLN02014001.1QWLN02014001.1QWLN02014001.1QWLN02014001.1

Sousa chinensis

Figure 2: Schematic representation of the exons found and validated with the CHfinder application. In brown areexons identified as coding for IgM CHs. In green exons for IgD, in blue exons for IgG, in red exons for IgE and inyellow exons for IgA. In each exon, the numbering of the CH encoding is indicated. The probability of certainty isalso expressed (1 is 100%). Exons not found with the CHfinder and that was found by the human review are unfilled.

from cetaceans. As can be deduced from the phylogenetic tree presented in the additional figure 9cetaceans have genes in each of the clans.

In previous publications, it was described in primates and rodents the presence of conservedV region sequences in the chains of T cell receptors (Olivieri et al., 2014c; Olivieri & Gambon-Deza, 2015). The sequences of V regions indicate probable evolutionary conservation of each one



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Table 2: Number of V genes in immunoglobulins and TCR loci

IGHV IGKV IGLV TRA/DV TRBV TRGCTursiops truncatus 47 4 37 15 8 2Physeter catodon 8 6 16 18 12 2Balaenoptera acutorostrata 6 7 18 17 12 3Monodon monoceros 9 1 13 13 10 2Lagenorhynchus obliquidens 5 3 17 9 7 2Orcinus orca 26 2 19 7 8 2Globicephala melas 11 7 13 10 7 2Lipotes vexillifer 13 5 11 11 10 2Neophocaena asiaeorientalis 15 6 23 9 11 2Delphinapterus leucas 11 2 16 9 9 3Phocoena sinus 10 5 10 11 11 2

of them. That is to say, orthologous from each of the V regions exist in neighbouring species.Something different from what happens with the V regions of antibodies where the emergence ofgenes by duplication and subsequent selection occurs. These results suggest a probable determin-ism in recognition of the V regions of chains of TCRs, perhaps mediated by the need to recognizeMHC molecules.

The deduced amino acid sequences of the V genes of the TRAV locus in primates and rodentsconform six significant clades, which in turn harbour 35 subclades in total. The sequences found inthe cetacean TRAV locus plus the consensus sequence of each primate clade were aligned. Whenconstructing the phylogenetic tree with this alignment, the presence of the primate consensussequences allows identifying if there are lines maintained with primates or if new ones are present.

The phylogenetic tree with the consensus sequences of each Primate clade in TRAV is in thefigure 4. Four sequences outside the clades correspond to Vδ sequences. All the others can beassigned to clades present in primates, indicating the conservation of these clades in evolution. Ofthe six main clades described in primates, II and IV do not have representatives in cetaceans. Of the35 subclades found in the TRAV loci of primates, only 15 are present. The results demonstrate aselective decrease in the germinal repertoire of exons V. This diminished repertoire can be specificto Cetaceans or inherited from the common ancestor they share with Artiodactyla. To clarifythis question, we obtained the Vα regions of the cow genome. As can be seen in the additionalfigure 10 the cow has sequences rooted with most of the primate clades indicating its evolutionaryconservation. Clades II and IV have representatives in the cow. These results indicate that Vαgenes losses occurred specifically in cetaceans.

The Vβ genes have an evolutionary pattern similar to that explained above for the Vα genes.In primates and rodents, there are nine main clades. These main clades encompass a total of 25subclades. The phylogenetic tree with the consensus sequences of each primate clade in TRBVis in the figure 5. There are some differences from the pattern described above for the TRAV.All the major primate clades except for clade III and IX have representatives in Cetaceans. The



https://doi.org/10.1101/2020.10.24.353342


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leu

ca

s-1

21

Turs

iops_

trunca

tus-

38


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

18

Globicephala_melas-129

Turs

iops_

trunca

tus-

37

Lagenorh

ynch

us_

obliq

uid

ens-

39

De

lph

ina

pte

rus_

leu

ca

s-1

02

Orcinus_orca-168

Turs

iops_

trunca

tus-

36

Tursio

ps_truncatu

s-146




Tu

rsio

ps_

trun

ca

tus-7

9

Ph

oco

en

a_

sin

us-1

17

Tu

rsio

ps_

tru

nca

tus-3

5

Orcinus_orca-95

Bos_taurus-6

Bos_taurus-17

Monodon_m

onoceros-177



Tursio

ps_trunca

tus-

30


Tu

rsio

ps

_tru

nc

atu

s-7

1

Ba

lae

no

pte

ra_

acu

toro

str

ata

-42

Turs

iops_

trunca

tus-

110

Bos_taurus-16

Lipote

s_vexillife

r-2

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

5

Glo

bice

phal

a_m

elas

-148



Orcinus_orca-174

Lipo

tes_

vexi

llife

r-11

3

Ph

yse

ter_

ca

tod

on

-41

De

lph

ina

pte

rus_

leu

ca

s-7

7

Bos_taurus-15



Mon

odon

_mon

ocer

os-3

4

Ph

oco

en

a_

sin

us-1

20

Orcinus_orca-58



Mo

no

do

n_

mo

no

ce

ros-1

57

Tu

rsio

ps_

trun

ca

tus-1

51


Orcinus_orca-57

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

7

Tursiops_tru

ncatus-1

47

Glo

bic

ephala

_m

ela

s-40

Bos_taurus-13

Bos_taurus-20

De

lph

ina

pte

rus_

leu

ca

s-1

05

Orcinus_orca-128


Clan I

Clan II

Artiodactylia Clade

Clan III

Figure 3: Figure present phylogenetic tree made with amino acid sequences obtained from the VH of cetaceans andcows. The consense sequence of each of the clans identified in the primates has been added. Taxa in red are sequencesfrom primates, green from cow and blue from cetaceans. The alignment of the sequences was performed with themafft program and the tree with fasttree using the LG matrix and gamma parameter. The visualization was made withthe Figtree program.

decrease in subclades of the TRBV loci concerning primates is smaller than in the TRAV loci (35to 15 versus 25 to 15). In the case of cetaceans, two subclades within the main clade II are not inprimates. As we did previously with the Vα exons, we compared the Vβ exons of cetaceans withthe Vβ from a cow (figure 11. Clades III and IX present exons in the cow, indicating that the lossis after the divergence of Artiodactyla. Also of the two new subclades found in cetaceans, onlyone of them is a related cow Vβ.

With the Vgenextractor we also obtained the deduced amino acid sequences of the Vγ ex-ons. Vγ genes in mammals are few in most species. In the phylogenetic trees carried out, theysuggest sequence conservation. In figure 6, we have schematically represented the results foundin cetaceans together with those found in cows and primates. The sequences obtained from theVγ exons are into three main clades. Clade II features two subclades. While primates and cowspresent sequences in all clades, cetaceans do not have sequences in Clade III.



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0.3

Clade_12


Clade_10

Lipotes_vexillife

r-22



Balaen

optera

_acuto

rostrat

a-50

Tursiops_tru

ncatus-122



Clade_17



Physeter_catodon-87

Lipotes_vexillife

r-117


Monodon_monoceros-84



Orcinus_orca-127

Globicephala_m

elas-114

Orcin

us_orca

-68

Clade_29

Neophocaen

a_asiaeorien

talis-51

Physete

r_catod

on-60

Clade_18

Balaenoptera_acutorostra

ta-8

Clade_21


Globic

ephala

_mela

s-91

Clade_31

Clade_14

Clade_6


Phocoena_sinus-85

Physeter_catodon-71




Clade_34

Phocoena

_sinus-58


Clade_19


Globicephala_m

elas-67

Clade_27

Clade_16

Physeter_catodon-70

Physeter_catodon-80


Clade_24

Physet

er_cat

odon-4

9



Clade_5




Balaenoptera_

acutorostrata-9

3

Physeter_catodon-72


Lageno

rhynchu

s_obliq

uidens-8

8

Clade_15

Clade_8

Tursiops_

truncatus-

90

Clade_3


ta-33


Clade_28


Clade_

23


Clade_25

Clade_22


Globicephala_

melas-52

Clade_13Phoco

ena_sinus-9

8

Phocoena_sinus-6

Physeter_catodon-74

Tursiops_t

runcat

us-99



Clade_11




Clade_7


Phocoena_sinus-110


Orcinus_orca-82



Orcinus_orca-123

Orcinus_orca-41

Tursiops_tru

ncatus-31

Physeter_catodon-38


Neophoc

aena_asi

aeorienta

lis-57

Physeter_catodon-73

Phocoe

na_sinu

s-56


Clade_20

Tursiops_truncatus-112Clade_2



Physeter_catodon-36


Physe

ter_catodon-34


3Clade_9

Physeter_catodon-77

Clade_30


Monodon_m

onoceros-108

Delph

inapte

rus_le

ucas-10

0


Clade_35

Clade_1

Clade_4



Clade_26


Orcinu

s_orca

-92


Phocoena_sinus-13




Clade_32




Tursiops_tru

ncatus-32

Clade_33




Phocoena_sinus-97


Phocoena_sinus-27



ta-7


Phocoena_sinus-61

Orcinus_orca-124

Monodon_m

onoceros-63

Physeter_catodon-21



Phocoena_sinus-46




4




Lagenorh

ynchus_o

bliquiden

s-89


Lipotes_vexillifer-4 Glo

bicephala_melas-125

I

II

III

IV

V

VI

Figure 4: Figure present phylogenetic tree made with amino acid sequences obtained from the Vα of cetaceans.The consense sequence of each of the subclades identified in the primates is represented. Taxa in red are consensussequences from primates. Main clades in which they share primate and cetacean sequences are indicated in greenroman numerals while those that do not have cetacean representation are in red. The alignment of the sequenceswas performed with the mafft program and the tree with fasttree using the LG matrix and gamma parameter. Thevisualization with the Figtree program.

3.3. MHC class I and IIIt searches for central exons of MHC class I and class II antigens in the genomes of cetaceans

were with MHCfinder program. Clusters of exons 2, 3 and 4 of MHC class I and that of 2 and 3of class II were probably viable genes. The appearance of loose exons is typical at these loci, andthey are part of pseudogenes. In all species, the studied MHC genes are on the same chromosome.There is an exception of one isolated class I gene that is on another chromosome.

In class I antigens we detect three evolutionary (lines Line 1, 2 and 3, figure 8). Representatives



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0.3

Globice

phala_m

elas-10

3Neophocaena_asiaeorientalis-96

Clade_10

Physe

ter_catodon-59

Phocoe

na_sin

us-83


Clade_1

Clade_17




Lipotes_vexillife

r-60

Clade_11


Clade_2

Clade_14



Orcinus_orca-55

Clade_21

Phocoena_sinus-1

Clade_20

Orcinu

s_orca

-102

Monodon_m

onoceros-4

Clade_

23


Orcinus_orca-28

Physeter_catodon-63

Physeter_catodon-68









Clade_7

Physeter_catodon-62


Globicephala_m

elas-54

Orcinus_orca-73

Clade_22

Balaenopte

ra_acutoros

trata-87

Physeter_catodon-70

Physeter_catodon-48



Balaenoptera_acutorostrata-98Phocoena_sinus-95

Clade_12




ta-22 P

hocoena_sinus-24

Orcinus_orca-11

Clade_13Clade_6

Phocoena_sinus-6

Orcinus_orca-45

Balaenop

tera_acuto

rostrata-1

05

Physeter_catodon-32


Physeter_

catodon-8

6

Phocoena_sinus-64

Clade_8

Physe

ter_catodon-15

Lagenorhy

nchus_

obliqu

idens-

101




Clade_16


Lipotes_vexillife

r-61

Orcinus_orca-36

Orcinus_orca-91



Physete

r_cato

don-8

2

Clade_18

Phocoena_sinus-77




Phocoena_sinus-18

Clade_19

Neophocaena_asia

eorientalis-1

7


Clade_4


Clade_3


Lagenorhynchu

s_obliquidens-

88




Phocoena_sinus-20


Lipotes_

vexillife

r-85




Clade_24



Globicephala_m

elas-13



Clade_5

Clade_15

Tursiops_truncatus-10Lipotes_vexillife

r-14


Physeter_catodon-99

Clade_9



Delphinapterus

_leucas-3

Tursiops_truncatu

s-100

Physeter_catodon-47

Clade_25



Monodon_m

onoceros-9

Phocoena_sinus-51

Lipotes_

vexillife

r-104

Neopho

caena_

asiaeor

ientalis

-84


9

Phocoena_sinus-42


I

II

IIIIV

V

VIVIIVII

VIII

IX

Figure 5: Figure present phylogenetic tree made with amino acid sequences obtained from the Vβ of cetaceans.The consense sequence of each of the subclades identified in the primates is represented. Taxa in red are consensussequences from primates. Main clades in which they share primate and cetacean sequences are indicated in greenroman numerals while those that do not have cetacean representation are in red. The alignment of the sequenceswas performed with the mafft program and the tree with fasttree using the LG matrix and gamma parameter. Thevisualization with the Figtree program.

of lines 1 and 3 are at one end with the class II genes. Line 1 has only one gene per species, whileline 3 there are usually two or more per species. The genes of line 2 are on another chromosome,and there is one gene per species.

MHC class II antigens have already been studied by other authors (Zhang et al., 2019). Theresults with the CHfinder are consistent with those published. In this case, there are no exonswith stop codons or with altered reading frames belonging to pseudogenes. Within the class twoantigens, we evidenced the absence of DP sequences. The position of genes on the chromosomeis in figure 7. From the end of the class I genes, a gene for the DR alpha chain appears first,



https://doi.org/10.1101/2020.10.24.353342


0.2

Bos_taurus

Tarsier(Primate)

Bos_taurus

Bos_taurus

I

IIa

b

III

Figure 6: The figure represents the phylogenetic tree obtained from the alignment of Vγ sequences of primates,cetaceans and cow. The clades are collapsed to reduce size. In red are the clades of primates, in blue of cetaceans andgreen of cow. The alignment of the sequences is with the mafft program and the tree with fasttree using the LG matrixand gamma parameter. The visualization is with the Figtree program

Table 3: Number of MHC class I and II genes in cetaceans

class I DPA DPB DQA DQB DRA DRB DMA DMB DOA DOBTursiops truncatus 7 - - 1 1 1 2 1 1 1 1Physeter catodon 3 - - 1 1 1 1 0 1 1 1Balaenoptera musculus 3 - - 1 1 1 2 1 1 1 1Monodon monoceros 5 - - 1 1 1 2 1 1 1 1Lagenorhynchus obliquidens 4 - - 1 1 1 2 1 1 1 1Orcinus orca 5 - - 1 1 1 2 1 1 1 1Globicephala melas 5 - - 1 1 1 1 1 1 1 1Lipotes vexillifer 6 - - 1 1 1 1 1 1 1 1Neophocaena asiaeorientalis 4 - - 1 1 1 2 1 1 1 1Delphinapterus leucas 3 - - 1 1 1 2 1 1 1 1Phocoena sinus 4 - - 1 1 1 2 1 1 1 1

followed most of the time by two DRB genes (these are in the chain complementary to that ofthe DRA gene). The DQA and DQB gene comes, the first being in the plus chain and the secondin the minus, then the DOA, DMA, DMB and DOB genes appear successively. Of the genomespresented in figure 7, all present structure described above except for Phisiter catodon in whichone of the DRB gene is lost, and the segment containing the DQ genes has undergone an inversion.Also, the DMA gene is not located.

4. Discussion

The study presented shows that cetaceans have constant regions genes from immunoglobulinand TCR genes similar to the rest of mammals. They also present histocompatibility antigenscommon to other mammals. The most significant differences are found in the number of V genes.An open test is why there are so many differences in the number of V genes in the germ line.Cetaceans are the mammalian species that have fewer genes than those described so far.

It remains unclear why two classes of light chains are necessary for mammals. The number of



https://doi.org/10.1101/2020.10.24.353342


exon2_DRB-0.844

exon3_DOB-0.983

exon2_DOB-0.963

exon3_DMB-0.952

exon2_DMB-0.986

exon3_DOA-0.996

exon2_DOA-1.0

exon3_DRB-0.975

exon2_DQA-1.0

exon3_DQA-1.0

exon3_DQB-0.519

exon2_DQB-0.961

exon2_DRB-0.835

exon3_DRB-0.975

exon3_DRA-1.0

exon2_DRA-0.998

exon1_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon3_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

NC_041231.1NC_041231.1NC_041231.1NC_041231.1NC_041231.1

exon1_I-0.996

exon2_I-0.972

exon3_I-0.96

exon1_I-1.0

exon2_I-1.0

exon3_I-1.0

exon1_I-1.0

exon2_I-1.0

exon3_I-1.0

exon1_I-1.0

exon2_I-1.0

exon3_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon2_DRA-0.999

exon3_DRA-0.999

exon3_DRB-0.974

exon2_DRB-0.997

exon3_DRB-0.969

exon2_DRB-0.914

exon2_DQA

exon3_DQA-1.0

exon3_DQB-0.767

exon2_DQB-0.937

exon2_DOA-0.999

exon3_DOA-0.999

exon2_DMA-0.999

exon3_DMA-0.93

exon2_DMB-0.981

exon3_DMB-0.945

exon2_DOB-0.946

exon3_DOB-0.983

exon2_DRB-0.9

NC_047043.1 NC_047043.1 NC_047043.1 NC_047043.1 NC_047043.1T. truncatus

P. catodon

exon2_DRB-0.741

exon3_DOB-0.976

exon2_DOB-0.874

exon3_DMB-0.924

exon2_DMB-0.979

exon3_DMA-0.859

exon2_DMA-0.999

exon3_DOA-0.999

exon2_DOA-0.999

exon2_DQB-0.83

exon3_DQB-0.752

exon3_DQA-1.0

exon2_DQA-1.0

exon2_DRB-0.825

exon3_DRB-0.986

exon2_DRB-0.674

exon3_DRB-0.963

exon3_DRA-0.999

exon2_DRA-0.999

exon1_I-1.0exon2_I-1.0exon3_I-1.0


exon2_I-1.0

exon3_I-0.96

exon2_I-0.965

exon1_I-0.997

NC_045773.1NC_045773.1NC_045773.1NC_045773.1NC_045773.1

P. sinus

exon1_I-1.0

exon2_I-1.0

exon3_I-1.0

exon1_I-1.0

exon1_I-0.97

exon2_I-1.0

exon1_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon2_DRA-0.999

exon3_DRA-0.999

exon3_DRB-0.907

exon3_DRB-0.979

exon3_DRB-0.941

exon2_DQB-0.773

exon2_DQA-1.0

exon3_DQA-1.0

exon2_DQB-0.973

exon3_DQB

exon2_DOA-1.0

exon3_DOA-0.997

exon2_DMA-1.0

exon3_DMA-0.954

exon2_DMB-0.999

exon3_DMB-0.778

exon2_DOB-0.93

exon3_DOB-0.976

Super_scaffold_7 Super_scaffold_7 Super_scaffold_7 Super_scaffold_7 Super_scaffold_7B. musculus

exon3_DRB-0.807

exon3_DOB-0.983

exon2_DOB-0.946

exon3_DMB-0.93

exon2_DMB-0.981

exon3_DMA-0.93

exon2_DMA-0.999

exon3_DOA-0.999

exon2_DOA-0.999

exon2_DQB-0.986

exon3_DQB-0.767

exon3_DQA-1.0

exon2_DQA-1.0

exon2_DRB-0.931

exon3_DRB-0.974

exon2_DRB-0.991

exon3_DRB-0.974

exon3_DRA-0.999

exon2_DRA-0.999

NW_020837975.1NW_020837975.1NW_020837975.1NW_020837975.1NW_020837975.1



NW_020838075.1

L. obliquidens

exon1_I-0.996

exon2_I-0.941

exon3_I-0.96

exon1_I-1.0

exon2_I-1.0

exon3_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon3_I-1.0

exon2_I-1.0

exon1_I-1.0

exon2_DRA-1.0

exon3_DRA-0.999

exon3_DRB-0.972

exon2_DRB-0.819

exon3_DRB-0.93

exon2_DRB-0.93

exon2_DQA-1.0

exon3_DQA-1.0

exon3_DQB-0.752

exon2_DQB-0.953

exon3_DOA-0.999

exon2_DOA

exon2_DMA-0.999

exon3_DMA-0.918

exon2_DMB-0.971

exon3_DMB-0.95

exon2_DOB-0.946

exon3_DOB-0.982

exon2_DRB-0.786

NW_021703780.1 NW_021703780.1 NW_021703780.1 NW_021703780.1 NW_021703780.1M. monoceros

DRA

DRB DRB

DQA

DQB

DOA DMA DOBDMB

DRA

DRB DQA

DQB DOA DOBDMB

DRA

DRB DRB

DQA

DQB

DOA DMA DOBDMB

DRA

DRB DRB

DQA

DQB

DOA DMA DOBDMB

DRA

DRB DRB

DQA

DQB

DOA DMA DOBDMB

DRA

DRB DRB

DQA

DQB

DOA DMA DOBDMB

Figure 7: Schematic representation of the exons found and validated with the MHCfinder application. In brown areexons identified as coding for MHC class I antigens. In red exons for MHC class II alpha chain antigens and greenexons for MHC class II alpha chain antigens. Each exon is numbered. The probability of certainty is also expressed(1 is 100%).

V regions is low. They have more genes for the lambda chain than for the kappa chain. Despitehaving a low number of genes, they have members in each of the clans described at the loci ofthese chains. Lambda light chains appear to have a different evolutionary process that kappa lightchains. Various clans can be identified and appear to be conserved among species as separate asmammals and reptiles (Olivieri et al., 2014a). These results suggest a specific functionality ofthese clans that are not currently known. It is known that in terrestrial vertebrates, no species haveexisted that have lost the lambda chain, but several evolutionary lines have lost the kappa chain(snakes, birds) further supports this hypothesis. In this case, the decrease in V regions is morepronounced in kappa, again suggesting the biological importance of lambda chains.

The number of VH genes is low in all species. A specific loss is evidenced since no specieshas VH genes belonging to Clan I. This fact is inherited from an ancestor with artiodactylia asdemonstrated by the absence in the cow. Some sequences present an elongation of the germsequence of the exon for VH that conditions a very long CDR3 region with disulfide bridges.These VHs are in a clade that is difficult to assign to a specific clan and probably corresponds to anew clan associated with artiodactylia and cetaceans. There are sequences for Clan II and Clan III

Exciting results are those found in the number and distribution of exons for Vα and Vβ. The



https://doi.org/10.1101/2020.10.24.353342


0.2

Phocoena_sinus-NC 045773.1-45

Tursiops_truncatus-NW 022983463.1-52


Neophocaena_asiaeorientalis-NW 020172595.1-46

Lipotes_vexillifer-NW 006774518.1-10


Tursiops_truncatus-NC 047043.1-14

Delphinapterus_leucas-NW 022098019.1-25


Globicephala_melas-NW 022134912.1-29

Orcinus_orca-NW 004438695.1-8






Lagenorhynchus_obliquidens-NW 020838075.1-36


Monodon_monoceros-NW 021703780.1-38




Physeter_catodon-NW 021146318.1-23


Balaenoptera_acutorostrata-NW 006732678.1-44



Physeter_catodon-NC 041231.1-2





























Line 1

Line 2

Line 3

Figure 8: Phylogenetic tree of MHC class I found in cetaceans. The sequence of the antigens is from the sequences ofthe exons found with the MHCfinder application. The alignment is with the mafft program, the tree with the fasttreeprogram (LG matrix, gamma parameter) and the visualization with Figtree.

presence of much fewer Vα genes is evidenced, not presenting clades or subclades that are presentin primates and rodents. Also, the V exons are related to specific primate clades. The absence oftwo main clades (Clades II and IV) at the TRAV loci is evident. Clade II in primates has threesubclades indicating that it is a clade with a large presence of V genes. Clade IV of primates isunique since it is a clade that only has one V gene per species, suggesting a specific recognition.This V gene is absent in Cetaceans. Major clades are also missing at the TRBV locus. In this case,they are III and IX clades. It is noteworthy that clade III is a clade with one Vβ gene per species.Clade IV Vα and clade III Vβ have similar evolutionary maintenance characteristics. The lostin cetaceans is suggestive that they may form a heterodimer with a specific function in primates.This function failed cetaceans, and therefore the clades have disappeared. If this were true, it leadsto the assumption that there are selective pairings between Vαs and Vβs. There are human dataon the presence of specific heterodimers shared between individuals (Tanno et al., 2020). With agreater number of studies in more species, it may be possible to confirm this hypothesis.

There is evidence that germline Vβ genes have predetermined affinity for MHC antigens . Thisevidence would support that the loss of Vβs may be due to the loss of some MHC gene. Cetaceansdo not provide conclusive data (Krovi et al., 2019). The MHC genes of cetaceans are similar to



https://doi.org/10.1101/2020.10.24.353342


those of other mammals.Is there a relationship between the V gene losses between the different loci? In previous pub-

lications, we have shown the existence of correlations between the number of V genes in locibetween species (Olivieri et al., 2014c). The presence of a correlation between the number of Vgenes for immunoglobulins and TCRs is intriguing. In the adaptive immune response, the major-ity of antibody responses are T-dependent, suggesting the possibility of functional relationshipsbetween the V genes of the antibodies and the Vα and Vβ genes of the TCR. New studies willbe necessary to know if the loss of VH clade I in cetaceans is related to the loss of clades andsubclades in the TRAV and TRBV loci.

5. References

References

Abadi, M., Barham, P., Chen, J., Chen, Z., Davis, A., Dean, J., Devin, M., Ghemawat, S., Irving, G., Isard, M.et al. (2016). Tensorflow: A system for large-scale machine learning. In 12th {USENIX} symposium on operatingsystems design and implementation ({OSDI} 16) (pp. 265–283).

Andresdottir, V., Magnadottir, B., Andresson, O. S., & Petursson, G. (1987). Subclasses of igg from whales. DevComp Immunol, 11, 801–806.

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6. Additional figures



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0.3

Tarsius_syrichta-Primate-860

Otolemur_garnettii-Primate-278


Microcebus_murinus-Primate-379

Daubentonia_madagascariensis-Primate-163



Papio_anubis-Primate-415



Gorilla_gorilla-Primate-1078

Pan_paniscus-Primate-347

Callithrix_jacchus-Primate-1201



Saimiri_boliviensis-Primate-1166






Chlorocebus_sabaeus-Primate-346

Vκ

Vλ

Clan II

Clan III

Clan I

Clan I

Clan II

Clan III

Clan IV

Clan V

Figure 9: The figure represents the phylogenetic tree obtained from the alignment of Vκ and Vλ sequences of primates,cetaceans and cow. The clades are collapsed to reduce size. In red are the clades of primates, in blue cetaceans and ingreen cow. The alignment of the sequences is with the mafft program and the tree with fasttree using the LG matrixand gamma parameter. The visualization was made with the Figtree program.



https://doi.org/10.1101/2020.10.24.353342


0.6

Delphinapterus_leucas

Clade_1

Clade_18

Clade_14

Clade_22

Clade_6


Clade_28

Clade_13

Clade_20

Bos_taurus

Clade_24

Clade_17

Clade_31

Clade_16

Clade_7

Bos_taurus

Clade_4

Clade_29

Clade_21

Clade_5

Clade_9

Bos_taurus

Clade_11

Clade_35

Bos_taurus

Clade_19

Bos_taurus

Clade_3

Clade_27Clade_26

Clade_32


Clade_10

Clade_12

Clade_30

Clade_23

Clade_34

Bos_taurus

Clade_33

Clade_2

Clade_8

Clade_25

Clade_15

TRDV

I

II

III

IV

V

VI

Figure 10: The figure represents the phylogenetic tree obtained from the alignment of Vα sequences of primates,cetaceans and cows. The clades are collapsed to reduce size. In red are the clades of primates, in blue cetaceans andgreen cow. The alignment of the sequences is with the mafft program and the tree with fasttree using the LG matrixand gamma parameter. The visualization is with the Figtree program



https://doi.org/10.1101/2020.10.24.353342


0.3

Clade_18

Bos_taurus

Clade_22

Clade_6

Bos_tauru

Bos_taurus

Clade_13

Bos_taurus

Clade_10

Lipotes_vexill ifer

Clade_4

Clade_15

Clade_23

Bos_taurus

Bos_taurus

Clade_21

Clade_19

Bos_taurus

Clade_2

Clade_14

Clade_24

Clade_25

Clade_9

Clade_5

Clade_7

Clade_17

Clade_11

Clade_8

Bos_taurus

Clade_1

Bos_taurus


Clade_12

Bos_taurus

Bos_taurus

Physeter_catodon

Clade_3

Clade_16

Clade_20

IV

V

VI

II

III

I

VII

VIII

IX

Figure 11: The figure represents the phylogenetic tree obtained from the alignment of Vβ sequences of primates,cetaceans and cows. The clades are collapsed to reduce size. In red are the clades of primates, in blue cetaceans andgreen cow. The alignment of the sequences is with the mafft program and the tree with fasttree using the LG matrixand gamma parameter. The visualization is with the Figtree program



https://doi.org/10.1101/2020.10.24.353342


0.2

Bos_taurus

Tarsier(Primate)

Bos_taurus

Bos_taurus

I

IIa

b

III



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0.3

Clade_18

Bos_taurus

Clade_22

Clade_6

Bos_tauru

Bos_taurus

Clade_13

Bos_taurus

Clade_10

Lipotes_vexill ifer

Clade_4

Clade_15

Clade_23

Bos_taurus

Bos_taurus

Clade_21

Clade_19

Bos_taurus

Clade_2

Clade_14

Clade_24

Clade_25

Clade_9

Clade_5

Clade_7

Clade_17

Clade_11

Clade_8

Bos_taurus

Clade_1

Bos_taurus


Clade_12

Bos_taurus

Bos_taurus

Physeter_catodon

Clade_3

Clade_16

Clade_20

IV

V

VI

II

III

I

VII

VIII

IX



https://doi.org/10.1101/2020.10.24.353342


0.6

Delphinapterus_leucas

Clade_1

Clade_18

Clade_14

Clade_22

Clade_6


Clade_28

Clade_13

Clade_20

Bos_taurus

Clade_24

Clade_17

Clade_31

Clade_16

Clade_7

Bos_taurus

Clade_4

Clade_29

Clade_21

Clade_5

Clade_9

Bos_taurus

Clade_11

Clade_35

Bos_taurus

Clade_19

Bos_taurus

Clade_3

Clade_27Clade_26

Clade_32


Clade_10

Clade_12

Clade_30

Clade_23

Clade_34

Bos_taurus

Clade_33

Clade_2

Clade_8

Clade_25

Clade_15

TRDV

I

II

III

IV

V

VI



https://doi.org/10.1101/2020.10.24.353342


20.0

Physeter_catodon-97

Ba

lae

no

pte

ra_

acu

toro

str

ata

-46


Tu

rsio

ps_

trun

ca

tus-7

4

Neophoca

ena_asi

aeori

enta

lis-1

07

Orcinus_orca-83

Tu

rsio

ps_

trun

ca

tus-7

5





Tu

rsio

ps_

trun

ca

tus-1

51 P

ho

co

en

a_

sin

us-1

24

Lipotes_vexilli

fer-4

Monodon_m

onoceros-1

27


Lage

norh

ynch

us_o

bliq

uide

ns-2

8

Monodon_m

onoceros-177

Tursiops_truncatus-181 Li

pote

s_ve

xilli

fer-

113


Orcinus_orca-171

Tu

rsio

ps_

trun

ca

tus-7

6

Orc

inus

_orc

a-27

Orcinus_orca-166

Mo

no

do

n_

mo

no

ce

ros-1

09

Tursio

ps_

trunca

tus-1

82

Ph

oco

en

a_

sin

us-1

04

Lip

ote

s_

ve

xillife

r-62

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

7

Turs

iops_

trunca

tus-

37

Glo

bice

phal

a_m

elas

-149

Glo

bice

phal

a_m

elas

-148

Bos_taurus-8

Lip

ote

s_

ve

xillife

r-63

Bos_taurus-6

Bos_taurus-16

Orcinus_orca-86

De

lph

ina

pte

rus_

leu

ca

s-7

7


Bos_taurus-22

Tursio

ps_truncatu

s-32

Bos_taurus-19

Phoco

ena_sin

us-8

2

Lagenorh

ynch

us_

obliq

uid

ens-

39

Bos_taurus-25


Tu

rsio

ps_

trun

ca

tus-1

50

Bos_taurus-11


Orcinus_orca-58

Balaenopte

ra_acuto

rostra

ta-1

La

ge

no

rhyn

ch

us_

ob

liqu

ide

ns-1

59

Orcinus_orca-92




Neophoca

ena_asia

eorie

nta

lis-152

Mo

no

do

n_

mo

no

ce

ros-7

8

Tursio

ps_trunca

tus-

30



Glo

bic

ephala

_m

ela

s-40



Tu

rsio

ps_

trun

ca

tus-1

53


Phocoena_sinus-93

Orc

inu

s_

orc

a-1

54

Orcinus_orca-49

Bos_taurus-9

Neophocaena_asiaeorientalis-55O

rcinus_orca-95

Del

phin

apte

rus_

leuc

as-3

3

De

lph

ina

pte

rus_

leu

ca

s-1

03

Bos_taurus-15


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

19

Glo

bic

ephala

_m

ela

s-111

Bos_taurus-23

Tu

rsio

ps

_tru

nc

atu

s-1

00

Tursiops_tru

ncatus-1

47

Turs

iops_

trunca

tus-

38

Ph

oco

en

a_

sin

us-1

17

Lagenorhynchus_obliquidens-130P

ho

co

en

a_

sin

us-6

4

Turs

iops_

trunca

tus-

36


Orcinus_orca-57

De

lph

ina

pte

rus_

leu

ca

s-1

05

Tursio

ps_

trunca

tus-1

84

Tursio

ps_truncatu

s-144

Tursio

ps_truncatu

s-145


42

Orc

inus_orc

a-1

06


Lip

ote

s_ve

xillifer-8

1

Monodon_m

onoceros-89


Bos_taurus-12O

rcin

us_o

rca-

114

Orc

inu

s_

orc

a-6

1

Ph

oco

en

a_

sin

us-1

20





Ph

oco

en

a_

sin

us-6

6

Tursio

ps_

trunca

tus-1

83

De

lph

ina

pte

rus_

leu

ca

s-1

02

Monodon_m

onocero

s-126

Tursio

ps_truncatu

s-146


Glo

bic

ep

ha

la_

me

las-7

3

Bos_taurus-18


Physeter_catodon-52

Ba

lae

no

pte

ra_

acu

toro

str

ata

-47

Bos_taurus-24

Bos_taurus-17

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

5

Tu

rsio

ps_

trun

ca

tus-7

9

Bos_taurus-21

Orcinus_orca-59


Bos_taurus-26

Orcinus_orca-174


Tu

rsio

ps_

trun

ca

tus-7

2

Cla

n I

I-P

rim

ate

-Co

nse

nsu

s1

0

Bos_taurus-14


De

lph

ina

pte

rus_

leu

ca

s-1

21 N

eo

ph

oca

en

a_

asia

eo

rie

nta

lis-1

01

Orcinus_orca-128

Neophoca

ena_asia

eorie

nta

lis-160



Orc

inus_

orca-1

25



Glo

bicephala

_mela

s-29


Turs

iops_

trunca

tus-

110

Tu

rsio

ps_

trun

ca

tus-6

9

Mon

odon

_mon

ocer

os-3

4

Mo

no

do

n_

mo

no

ce

ros-1

57



Ba

lae

no

pte

ra_

acu

toro

str

ata

-42



Orcinus_orca-167

Neophoca

ena_asi

aeori

enta

lis-1

08


Lipote

s_vexillife

r-2

Ph

oco

en

a_

sin

us-1

23

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

18


Tu

rsio

ps_

tru

nca

tus-3

5

Tu

rsio

ps

_tru

nc

atu

s-7

1

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

16

Ph

yse

ter_

ca

tod

on

-45

Orc

inu

s_

orc

a-1

15

Orcinus_orca-84

Ph

yse

ter_

ca

tod

on

-41

Bos_taurus-20

Phocoena_sinus-53

Delp

hin

apte

rus_

leuca

s-94

Bos_taurus-10

Orcinus_orca-180

Ne

op

ho

ca

en

a_

asia

eo

rien

talis

-12

2

Orc

inus

_orc

a-11

2

Bos_taurus-7

Tu

rsio

ps

_tru

nc

atu

s-7

0

Orcinus_orca-85

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

8

Bos_taurus-13G

lob

ice

ph

ala

_m

ela

s-1

58

Orcinus_orca-168

Lip

ote

s_ve

xillifer-8

0

De

lph

ina

pte

rus_

leu

ca

s-1

56

Ph

yse

ter_

ca

tod

on

-44

Orc

inu

s_

orc

a-1

55

Tursio

ps_truncatu

s-31

Clan I

Clan IIIClan

II



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0.3

Globice

phala_m

elas-10

3Neophocaena_asiaeorientalis-96

Clade_10

Physe

ter_catodon-59

Phocoe

na_sin

us-83


Clade_1

Clade_17




Lipotes_vexillife

r-60

Clade_11


Clade_2

Clade_14



Orcinus_orca-55

Clade_21

Phocoena_sinus-1

Clade_20

Orcinu

s_orca

-102

Monodon_m

onoceros-4

Clade_

23


Orcinus_orca-28

Physeter_catodon-63

Physeter_catodon-68









Clade_7

Physeter_catodon-62


Globicephala_m

elas-54

Orcinus_orca-73

Clade_22

Balaenopte

ra_acutoros

trata-87

Physeter_catodon-70

Physeter_catodon-48Globicephala_melas-38


Balaenoptera_acutorostrata-98Phocoena_sinus-95

Clade_12




ta-22 P

hocoena_sinus-24

Orcinus_orca-11

Clade_13

Clade_6

Phocoena_sinus-6

Orcinus_orca-45

Balaenop

tera_acuto

rostrata-1

05

Physeter_catodon-32


Physeter_

catodon-8

6

Phocoena_sinus-64

Clade_8

Physe

ter_catodon-15

Lagenorhy

nchus_

obliqu

idens-

101




Clade_16


Lipotes_vexillife

r-61

Orcinus_orca-36

Orcinus_orca-91



Physete

r_cato

don-8

2

Clade_18

Phocoena_sinus-77




Phocoena_sinus-18

Clade_19

Neophocaena_asia

eorientalis-1

7


Clade_4


Clade_3


Lagenorhynchu

s_obliquidens-

88




Phocoena_sinus-20


Lipotes_

vexillife

r-85




Clade_24



Globicephala_m

elas-13



Clade_5

Clade_15

Tursiops_truncatus-10Lipotes_vexillife

r-14


Physeter_catodon-99

Clade_9



Delphinapterus

_leucas-3

Tursiops_truncatu

s-100

Physeter_catodon-47

Clade_25



Monodon_m

onoceros-9

Phocoena_sinus-51

Lipotes_

vexillife

r-104

Neopho

caena_

asiaeor

ientalis

-84


9

Phocoena_sinus-42


I

II

IIIIV

V

VIVIIVII

VIII

IX



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0.3

Clade_12


Clade_10

Lipotes_vexillife

r-22



Balaen

optera

_acuto

rostrat

a-50

Tursiops_tru

ncatus-122



Clade_17



Physeter_catodon-87

Lipotes_vexillife

r-117





Orcinus_orca-127

Globicephala_m

elas-114

Orcin

us_orca

-68

Clade_29

Neophocaen

a_asiaeorien

talis-51

Physete

r_catod

on-60

Clade_18


ta-8

Clade_21


Globic

ephala

_mela

s-91

Clade_31

Clade_14

Clade_6


Phocoena_sinus-85

Physeter_catodon-71




Clade_34

Phocoena

_sinus-58

Balaenoptera_acutorostrata-78Clade_19


Globicephala_m

elas-67

Clade_27

Clade_16

Physeter_catodon-70

Physeter_catodon-80


Clade_24

Physet

er_cat

odon-4

9



Clade_5




Balaenoptera_

acutorostrata-9

3

Physeter_catodon-72


Lageno

rhynchu

s_obliq

uidens-8

8

Clade_15

Clade_8

Tursiops_

truncatus-

90

Clade_3


ta-33


Clade_28


Clade_

23


Clade_25

Clade_22


Globicephala_

melas-52

Clade_13Phoco

ena_sinus-9

8

Phocoena_sinus-6

Physeter_catodon-74

Tursiops_t

runcat

us-99



Clade_11




Clade_7


Phocoena_sinus-110


Orcinus_orca-82



Orcinus_orca-123

Orcinus_orca-41

Tursiops_tru

ncatus-31

Physeter_catodon-38


Neophoc

aena_asi

aeorienta

lis-57

Physeter_catodon-73

Phocoe

na_sinu

s-56


Clade_20

Tursiops_truncatus-112Clade_2



Physeter_catodon-36

Lipotes_vexillifer-106Physe

ter_catodon-34


3Clade_9

Physeter_catodon-77

Clade_30


Monodon_m

onoceros-108

Delph

inapte

rus_le

ucas-10

0


Clade_35

Clade_1

Clade_4



Clade_26


Orcinu

s_orca

-92


Phocoena_sinus-13




Clade_32




Tursiops_tru

ncatus-32

Clade_33




Phocoena_sinus-97


Phocoena_sinus-27



ta-7


Phocoena_sinus-61

Orcinus_orca-124

Monodon_m

onoceros-63

Physeter_catodon-21



Phocoena_sinus-46




4




Lagenorh

ynchus_o

bliquiden

s-89


Lipotes_vexillifer-4 Glo

bicephala_melas-125

I

II

III

IV

V

VI



https://doi.org/10.1101/2020.10.24.353342


0.3




Microcebus_murinus-Primate-379




Papio_anubis-Primate-415



Gorilla_gorilla-Primate-1078

Pan_paniscus-Primate-347




Saimiri_boliviensis-Primate-1166






Chlorocebus_sabaeus-Primate-346

Vκ

Vλ

Clan II

Clan III

Clan I

Clan I

Clan II

Clan III

Clan IV

Clan V



https://doi.org/10.1101/2020.10.24.353342


exon3_A-0.999

exon2_A-0.989

exon1_A-0.926

exon3_E-0.995

exon3_E-0.948

exon2_E-0.99

exon1_E-0.943

exon3_G-0.956

exon2_G-1.0

exon1_G-0.998

exon1_G-0.998

exon1_G-0.999

exon2_G-1.0

exon2_G-0.419

exon3_G-0.967

exon2_G-0.988

exon1_G-0.999

exon3_D-0.949

exon1_M-0.941

exon4_M-0.386

exon3_M-0.923

exon2_M-0.981

exon1_M-0.963

NC_041224.1NC_041224.1NC_041224.1NC_041224.1NC_041224.1

exon3_A-1.0

exon2_A-0.781

exon1_A-0.977

exon4_E-0.982

exon3_E-0.995

exon2_E-0.988

exon1_E-0.998

exon3_G-0.892

exon2_G-1.0

exon1_G-0.999

exon2_G-1.0

exon2_G-1.0

exon1_G-0.999

exon3_D-1.0

exon2_D-0.991

exon1_M-0.609

exon4_M-1.0

exon2_M-0.696

exon1_M-0.943

NW_004438415.1NW_004438415.1NW_004438415.1NW_004438415.1NW_004438415.1

exon3_A-1.0

exon2_A-0971

exon1_A

exon4_E-1.0

exon3_E-0.902

exon2_E-0.996

exon1_E-0.992

exon3_G-0.913

exon2_G-1.0

exon1_G-0.999

exon3_G-0.942

exon2_G-1.0

exon1_G-0.999

exon1_M-0.948

exon4_M-0.1

exon3_M-0.673

exon2_M-0.971

exon1_M-0.986

exon3_G-0.987

exon2_G-1.0

exon1_G-1.0

exon3_A-1.0

exon2_A-0.957

exon1_A-1.0

exon4_E-0.895

exon3_E-1.0

exon2_E-0.989

exon1_E-0.999

exon3_G-0.987

exon2_G-1.0

exon1_G-0.999

exon1_G-1.0

exon3_D-1.0

exon2_D-0.981

exon2_D

exon4_M-1.0

exon3_M-0.436

exon3_M-338

exon2_M-0.673

exon1_M-0.892

NW_006726265.1NW_006726265.1NW_006726265.1NW_006726265.1NW_006726265.1 gap

Balaenoptera acutorostrata

exon1_G-1.0

exon2_G-1.0

exon3_G-0.994

exon1_G-1.0

exon2_G-1.0

exon3_G-0.987

NW_006731512.1

exon3_D-0.999

exon2_D-0.988

Super_scaffold_11Super_scaffold_11Super_scaffold_11Super_scaffold_11

Balaenoptera musculus

φ? φ?

Physeter catodon

exon1_M-0.991

exon2_M-0.906

exon3_M-0.442

exon4_M-1.0

exon1_M-0.985

exon2_D-0.987

exon3_D-1.0

NW_006783775.1 NW_006783775.1

exon1_G-1.0

exon2_G-1.0

exon3_G-0.967

exon1_E-0.998

exon2_E-0.979

exon3_E-0.999

exon4_E-0.948

exon1_A-1.0

exon2_A-0.538

exon3_A-1.0

NW_006778806.1 NW_006778806.1

Lipotes vexillifer

exon3_A-1.0

exon2_A

exon1_A-1.0

exon4_E-0.975

exon3_E-0.998

exon2_E-0.963

exon1_E-0.999

exon2_G-1.0

exon2_G-0.998

exon1_G-0.998

exon2_G-1.0

exon2_G-0.999

exon1_G-0.999

exon3_D-1.0

exon2_D-0.994

exon1_M-0.954

exon4_M-1.0

exon3_M-0.477

exon2_M-0.89

exon1_M-0.952

NC_045764.1NC_045764.1NC_045764.1NC_045764.1NC_045764.1

Phocoena sinus

exon1_M-0.979

exon2_M-0.926

exon3_M-0.442

exon4_M-1.0

exon1_M-0.626

exon2_D-0.994

exon3_D-1.0

exon1_G-0.999

exon2_G-1.0

exon3_G-0.901

exon1_G-0.999

exon2_G-1.0

exon3_G-0.908

exon1_E-0.998

exon2_E-0.984

exon3_E-0.995

exon4_E-0.977

exon1_A-1.0

exon2_A-0.79

exon3_A-1.0

NC_047035.1 NC_047035.1 NC_047035.1 NC_047035.1 NC_047035.1

Tursiops_truncatus

Orcinus orca

exon3_A-1.0

exon2_A-0.712

exon1_A-0.859

exon4_E-0.951

exon3_E-0.999

exon2_E-0.989

exon1_E-0.995

exon3_G-0.74

exon2_G-1.0

exon1_G-0.999

exon3_G-0.844

exon2_G-1.0

exon1_G-0.999

exon3_D-1.0

exon2_D-0.994

exon1_M-0.905

exon4_M-1.0

exon3_M-0.999

exon2_M-0.911

exon1_M-0.678

QWLN02014001.1QWLN02014001.1QWLN02014001.1QWLN02014001.1QWLN02014001.1

Sousa chinensis



https://doi.org/10.1101/2020.10.24.353342


4.0

Physeter_catodon

Eschrichtius_robustus

Pontoporia_blainvillei

Balaenoptera_musculus

Mesoplodon_bidens

Tursiops_truncatus

Lagenorhynchus_obliquidens


Monodon_monoceros

Lipotes_vexillifer

Phocoena_phocoena

Inia_geoffrensis

Globicephala_melas

Sousa_chinensis

Tursiops_aduncus

Megaptera_novaeangliae

Phocoena_sinus

Orcinus_orca

Kogia_breviceps

Eubalaena_japonica

9,91

25,42

33,04

26,34

18,87

33,5

25,9

24,72

18,39

9,91

33,5

6,74

11,14

15,54

5,68

3,6

15,36

14,29

15,37

Delphinidae

Odontoceti

Physeteridae

Iniidae

Pontoporiidae

Lipotidae

Phocoenidae

Monodontidae

Mysticeti



https://doi.org/10.1101/2020.10.24.353342


0.2

























































Line 1

Line 2

Line 3



https://doi.org/10.1101/2020.10.24.353342


Bos_taurus-26

Glo

bic

ep

ha

la_

me

las-1

58

Tursio

ps_truncatu

s-32

Tu

rsio

ps

_tru

nc

atu

s-1

00


42

Del

phin

apte

rus_

leuc

as-3

3

Ne

op

ho

ca

en

a_

asia

eo

rien

talis

-12

2

Neophoca

ena_asi

aeori

enta

lis-1

08


Monodon_m

onocero

s-126


Tursio

ps_truncatu

s-145

Orcinus_orca-171

Orcinus_orca-166


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

16

Lage

norh

ynch

us_o

bliq

uide

ns-2

8

Tu

rsio

ps_

trun

ca

tus-7

6


Bos_taurus-21


Physeter_catodon-97

Orcinus_orca-59

Bos_taurus-10

La

ge

no

rhyn

ch

us_

ob

liqu

ide

ns-1

59

Tursio

ps_truncatu

s-31


Bos_taurus-23


Phoco

ena_sin

us-8

2

Bos_taurus-9

Tu

rsio

ps_

trun

ca

tus-6

9


Tu

rsio

ps_

trun

ca

tus-1

50

Lip

ote

s_ve

xillifer-8

1


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

19

Orcinus_orca-167

Orcinus_orca-86



Lip

ote

s_

ve

xillife

r-62

Glo

bic

ephala

_m

ela

s-111

Bos_taurus-19


Bos_taurus-11


Delp

hin

apte

rus_

leuca

s-94

De

lph

ina

pte

rus_

leu

ca

s-1

03

Orc

inu

s_

orc

a-1

15


Orc

inus

_orc

a-11

4

Bos_taurus-24


Bos_taurus-18



Ph

oco

en

a_

sin

us-6

4

Ba

lae

no

pte

ra_

acu

toro

str

ata

-46


Ph

yse

ter_

ca

tod

on

-44

Orc

inus

_orc

a-27

Monodon_m

onoceros-89

De

lph

ina

pte

rus_

leu

ca

s-1

56

Cla

n I

I-P

rim

ate

-Co

nse

nsu

s1

0

Mo

no

do

n_

mo

no

ce

ros-7

8

Ph

oco

en

a_

sin

us-6

6

Mo

no

do

n_

mo

no

ce

ros-1

09

Neophoca

ena_asi

aeori

enta

lis-1

07

Tu

rsio

ps_

trun

ca

tus-7

2

Bos_taurus-14

Neophoca

ena_asia

eorie

nta

lis-152

Bos_taurus-7

Tu

rsio

ps_

trun

ca

tus-1

53

Tu

rsio

ps

_tru

nc

atu

s-7

0


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-1

01

Phocoena_sinus-93

Tursio

ps_

trunca

tus-1

82

Tu

rsio

ps_

trun

ca

tus-7

4


Glo

bicephala

_mela

s-29


Orc

inu

s_

orc

a-1

55

Glo

bice

phal

a_m

elas

-149

Physeter_catodon-52

Ph

oco

en

a_

sin

us-1

23

Ba

lae

no

pte

ra_

acu

toro

str

ata

-47

Orc

inu

s_

orc

a-1

54

Bos_taurus-8


Ph

oco

en

a_

sin

us-1

04

Orc

inu

s_

orc

a-6

1

Orc

inus_orc

a-1

06

Glo

bic

ep

ha

la_

me

las-7

3

Phocoena_sinus-53

Lip

ote

s_

ve

xillife

r-63

Tursio

ps_truncatu

s-144

Tu

rsio

ps_

trun

ca

tus-7

5

Ph

oco

en

a_

sin

us-1

24


Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

8

Monodon_m

onoceros-1

27

Orcinus_orca-83

Orcinus_orca-180


Orcinus_orca-92


Bos_taurus-22

Bos_taurus-25

Balaenopte

ra_acuto

rostra

ta-1


Lip

ote

s_ve

xillifer-8

0

Tursio

ps_

trunca

tus-1

83

Orcinus_orca-85

Orc

inus

_orc

a-11

2

Bos_taurus-12


Orcinus_orca-49


Neophoca

ena_asia

eorie

nta

lis-160


Orcinus_orca-84

Lipotes_vexilli

fer-4

Orc

inus_

orca-1

25

Ph

yse

ter_

ca

tod

on

-45

Tursio

ps_

trunca

tus-1

84

De

lph

ina

pte

rus_

leu

ca

s-1

21

Turs

iops_

trunca

tus-

38

Tursiops_truncatus-99N

eo

ph

oca

en

a_

asia

eo

rie

nta

lis-1

18


Turs

iops_

trunca

tus-

37

Lagenorh

ynch

us_

obliq

uid

ens-

39

De

lph

ina

pte

rus_

leu

ca

s-1

02

Orcinus_orca-168

Turs

iops_

trunca

tus-

36

Tursio

ps_truncatu

s-146




Tu

rsio

ps_

trun

ca

tus-7

9

Ph

oco

en

a_

sin

us-1

17

Tu

rsio

ps_

tru

nca

tus-3

5

Orcinus_orca-95

Bos_taurus-6

Bos_taurus-17

Monodon_m

onoceros-177



Tursio

ps_trunca

tus-

30


Tu

rsio

ps

_tru

nc

atu

s-7

1

Ba

lae

no

pte

ra_

acu

toro

str

ata

-42

Turs

iops_

trunca

tus-

110

Bos_taurus-16

Lipote

s_vexillife

r-2

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

5

Glo

bice

phal

a_m

elas

-148



Orcinus_orca-174

Lipo

tes_

vexi

llife

r-11

3

Ph

yse

ter_

ca

tod

on

-41

De

lph

ina

pte

rus_

leu

ca

s-7

7

Bos_taurus-15



Mon

odon

_mon

ocer

os-3

4

Ph

oco

en

a_

sin

us-1

20

Orcinus_orca-58



Mo

no

do

n_

mo

no

ce

ros-1

57

Tu

rsio

ps_

trun

ca

tus-1

51


Orcinus_orca-57

Ne

op

ho

ca

en

a_

asia

eo

rie

nta

lis-6

7

Tursiops_tru

ncatus-1

47

Glo

bic

ephala

_m

ela

s-40

Bos_taurus-13

Bos_taurus-20

De

lph

ina

pte

rus_

leu

ca

s-1

05

Orcinus_orca-128


Clan I

Clan II

Artiodactylia Clade

Clan III



https://doi.org/10.1101/2020.10.24.353342


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Immunoglobulins, MHC and T Cell receptors genes in ......2020/10/24 · Immunoglobulins, MHC and T Cell receptors genes in Cetaceans Francisco Gambon-Deza´ Servicio Gallego de Salud