genomic analysis of the novel mycobacteriophage bromden

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Hope College Digital Commons @ Hope College 17th Annual Celebration of Undergraduate Research and Creative Performance (2018) Celebration of Undergraduate Research and Creative Performance 4-13-2018 Genomic Analysis of the Novel Mycobacteriophage Bromden Kaitlyn Lein Kimberly Paquee Timbree Pederson Mahew Switalski Carter Smiley See next page for additional authors Follow this and additional works at: hps://digitalcommons.hope.edu/curcp_17 Part of the Biology Commons is Poster is brought to you for free and open access by the Celebration of Undergraduate Research and Creative Performance at Digital Commons @ Hope College. It has been accepted for inclusion in 17th Annual Celebration of Undergraduate Research and Creative Performance (2018) by an authorized administrator of Digital Commons @ Hope College. For more information, please contact [email protected]. Recommended Citation Repository citation: Lein, Kaitlyn; Paquee, Kimberly; Pederson, Timbree; Switalski, Mahew; Smiley, Carter; Oonk, Emma; Baird, Darby; Van Wyk, Brooke; Hemesath, Lilly; Meder, Abigail; Orndorff, Madelyn; and Grimes, Megan, "Genomic Analysis of the Novel Mycobacteriophage Bromden" (2018). 17th Annual Celebration of Undergraduate Research and Creative Performance (2018). Paper 20. hps://digitalcommons.hope.edu/curcp_17/20 April 13, 2018. Copyright © 2018 Hope College, Holland, Michigan.

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Hope CollegeDigital Commons @ Hope College17th Annual Celebration of UndergraduateResearch and Creative Performance (2018)

Celebration of Undergraduate Research andCreative Performance

4-13-2018

Genomic Analysis of the NovelMycobacteriophage BromdenKaitlyn Lein

Kimberly Paquette

Timbree Pederson

Matthew Switalski

Carter Smiley

See next page for additional authors

Follow this and additional works at: https://digitalcommons.hope.edu/curcp_17

Part of the Biology Commons

This Poster is brought to you for free and open access by the Celebration of Undergraduate Research and Creative Performance at Digital Commons @Hope College. It has been accepted for inclusion in 17th Annual Celebration of Undergraduate Research and Creative Performance (2018) by anauthorized administrator of Digital Commons @ Hope College. For more information, please contact [email protected].

Recommended CitationRepository citation: Lein, Kaitlyn; Paquette, Kimberly; Pederson, Timbree; Switalski, Matthew; Smiley, Carter; Oonk, Emma; Baird,Darby; Van Wyk, Brooke; Hemesath, Lilly; Meder, Abigail; Orndorff, Madelyn; and Grimes, Megan, "Genomic Analysis of the NovelMycobacteriophage Bromden" (2018). 17th Annual Celebration of Undergraduate Research and Creative Performance (2018). Paper 20.https://digitalcommons.hope.edu/curcp_17/20April 13, 2018. Copyright © 2018 Hope College, Holland, Michigan.

Student Author(s)Kaitlyn Lein, Kimberly Paquette, Timbree Pederson, Matthew Switalski, Carter Smiley, Emma Oonk, DarbyBaird, Brooke Van Wyk, Lilly Hemesath, Abigail Meder, Madelyn Orndorff, and Megan Grimes

This poster is available at Digital Commons @ Hope College: https://digitalcommons.hope.edu/curcp_17/20

Gen

omic

Ana

lysi

s of

Nov

el M

ycob

acte

rioph

age

Bro

mde

nK

aitly

n Le

in, K

imbe

rly P

aque

tte, T

imbr

ee P

eder

son,

Mat

thew

Sw

itals

ki, C

arte

r Sm

iley,

Em

ma

Oon

k, D

arby

Bai

rd, B

rook

e V

an W

yk, L

illy

Hem

esat

h, A

biga

il M

eder

, Mad

elyn

Orn

dorff

, Meg

an G

rimes

. M

ento

rs: D

r. Jo

seph

Stu

key

Dep

artm

ent o

f Bio

logy

, Hop

e C

olle

ge, H

olla

nd, M

I

I.A

bstr

act

Twen

ty n

ew m

ycob

acte

rioph

ages

wer

e is

olat

ed fr

om s

oil s

ampl

es

colle

cted

aro

und

the

stat

e of

Mic

higa

n an

d ot

her p

arts

of t

he U

nite

d S

tate

s. A

ll ph

ages

wer

e ca

pabl

e of

infe

ctin

g M

ycob

acte

rium

sm

egm

atis

and

wer

e is

olat

ed th

roug

h ei

ther

enr

ichm

ent o

r dire

ct

plat

ing

at 3

2℃. A

var

iety

of p

laqu

e m

orph

olog

ies

wer

e pr

oduc

ed

base

d on

siz

e, s

hape

, and

cla

rity;

bot

h ly

tic a

nd te

mpe

rate

pha

ges

are

repr

esen

ted

in th

is c

olle

ctio

n. T

he m

ycob

acte

rioph

age,

B

rom

den,

was

cho

sen

as o

ne o

f tw

o ph

ages

for c

ompl

ete

geno

me

sequ

enci

ng a

nd c

ompa

rativ

e ge

nom

ic a

naly

ses.

The

pre

dom

inan

t pl

aque

pro

duce

d by

Bro

mde

n af

ter 4

8 ho

urs

at 3

2℃ is

0.5

mm

in

diam

eter

, circ

ular

, and

cle

ar. T

he g

enom

e of

Bro

mde

n is

70.

2 K

b,

58.2

% G

C, a

nd c

onta

ins

119

gene

s. B

rom

den’

s co

mpl

ete

geno

me

sequ

ence

indi

cate

s a

rela

tions

hip

to m

ycob

acte

rioph

ages

of c

lust

er

L, a

nd s

trong

est s

imila

rity

to m

ycob

acte

rioph

age

Dyo

Eda

fos

of

subc

lust

er L

4, w

hich

is th

e on

ly o

ther

mem

ber o

f the

L4

subc

lust

er o

f m

ycob

acte

rioph

ages

. The

two

geno

mes

alig

n at

onl

y 85

% id

entit

y ov

er 8

7% o

f the

sho

rter B

rom

den,

with

the

larg

est d

iffer

ence

bei

ng

an 8

.5 k

b se

ctio

n fo

und

in D

yoE

dafo

s bu

t mis

sing

in B

rom

den.

Thi

s ac

coun

ts fo

r the

diff

eren

ce in

thei

r gen

e nu

mbe

rs, a

s D

yoE

dafo

s ha

s 33

mor

e ge

nes

than

Bro

mde

n. A

uto-

anno

tatio

n in

dica

ted

ther

e ar

e 13

pos

sibl

e tR

NA

gen

es in

Bro

mde

n. T

he G

C c

onte

nt o

f Bro

mde

n (5

8.2%

) is

low

com

pare

d to

mos

t oth

er c

lust

ers

of

myc

obac

terio

phag

es a

s w

ell a

s th

eir c

omm

on h

ost,

M. s

meg

mat

is

(67.

4%).

The

othe

r clu

ster

s w

ith re

lativ

ely

low

GC

con

tent

als

o ha

ve

few

mem

bers

, sug

gest

ing

that

thes

e ph

ages

may

mor

e re

adily

infe

ct

othe

r bac

teria

l hos

ts w

ith lo

wer

GC

con

tent

. A d

etai

led

anal

ysis

of

the

com

plet

e ge

nom

e se

quen

ces

and

com

paris

on w

ith s

eque

nced

m

ycob

acte

rioph

ages

is th

e su

bjec

t of t

he s

econ

d se

mes

ter o

f the

ye

arlo

ng c

ours

e an

d is

pre

sent

ed.

II.In

trod

uctio

nM

ycob

acte

rioph

age

Bio

logy

and

Gen

omic

s-

Nea

rly 9

,700

myc

obac

terio

phag

es h

ave

been

isol

ated

, of

whi

ch 1

,577

hav

e be

en s

eque

nced

and

cha

ract

eriz

ed-

Pha

ges

allo

w fo

r stu

dy o

f myc

obac

teria

thro

ugh

enha

nced

ge

netic

s, u

nder

stan

ding

of h

ow p

hage

con

tribu

te to

bac

teria

l bi

olog

ical

pro

cess

es-

Full

geno

me

sequ

ence

s of

pha

ges

reve

al n

ovel

func

tions

, ge

nes,

and

evo

lutio

n of

myc

obac

teria

l pha

ge a

nd h

osts

Dr.

Jose

ph S

tuke

yD

epar

tmen

t of B

iolo

gyst

ukey

@ho

pe.e

du

III.P

hage

Gen

omic

s R

esea

rch

2017

-201

8

2017

-201

8 Ph

age

Gen

omic

s R

esea

rch

Stud

ents

(Bro

mde

n gr

oup)

and

Pha

ge N

ames

Ack

now

ledg

emen

tsU

nive

rsity

of P

ittsb

urgh

Hat

full

Lab

How

ard

Hug

hes

Med

ical

In

stitu

te

SE

A-P

HA

GE

S P

rogr

am

Hop

e C

olle

ge D

epar

tmen

t of

Bio

logy

TA’s

: Meg

an G

rimes

and

M

adel

yn O

rndo

rff

IV.P

hysi

cal a

nd G

enom

ic C

hara

cter

istic

s

Figu

re 6

- Fr

eque

ncy

of G

C c

onte

nt

in B

rom

den

gene

s (L

eft)

Cal

cula

ting

the

GC

con

tent

for e

ach

gene

in B

rom

den

reve

aled

that

ther

e ar

e no

influ

entia

l out

liers

, but

ther

e ar

e si

x st

atis

tical

ly s

igni

fican

t gen

es.

Gen

es 6

1(50

.12)

, 105

(48.

33),

and

109(

49.7

5) a

re b

elow

2 s

tand

ard

devi

atio

ns fo

r the

GC

con

tent

. G

enes

22

(64.

73),

68(6

7.09

), an

d 10

1(66

.67)

ar

e ab

ove

two

stan

dard

dev

iatio

ns fr

om

the

mea

n.

95%

CI:

[50.

3, 6

4.78

5]. M

ean:

57.

5Fa

ndom

Imag

e

Abb

y M

eder

Boo

gey1

Han

nah

DeV

ore

Dee

rs

Julia

Wils

onP

hout

teA

mel

ia W

aalk

esS

elco

uth

Sar

ah O

len

Laet

aH

anna

h C

izau

skas

Bro

mde

n

Kai

tlyn

Lein

Ladi

ana

Ced

ric P

orte

rP

hutb

ol

Ana

Per

ecki

Sat

urnu

sM

atth

ew S

wita

lski

Mas

todo

n

Lydi

a D

ough

tyTh

yatir

aC

arte

r Sm

iley

Nep

hario

us

Tim

brer

e P

eder

son

Zuri

Bro

oke

Van

Wyk

Oni

sm

Lilly

Hem

esat

hLo

nder

Dar

by B

aird

M

alel

dil

Adr

iana

Mira

belli

Gra

ves

Kim

Paq

uette

P

upil

Zach

Wyl

ie

John

nyC

ache

Que

stio

n: W

hat M

ycob

acte

rium

spe

cies

doe

s B

rom

den

com

mon

ly in

fect

?M

etho

d: L

ook

at th

e ge

ne B

LAS

T, u

nusu

al g

enes

in p

hage

s, c

odon

usa

ge b

ias,

and

GC

con

tent

to fi

nd g

enes

that

hav

e be

en s

tole

n fro

m

host

s.R

esul

ts:

V.Po

tent

ial p

rimar

y ho

sts

Bro

mde

n C

hara

cter

istic

sIs

olat

ed v

ia d

irect

pla

ting

proc

edur

e fro

m m

oist

soi

l sam

ple,

col

lect

ed

by H

anna

h C

izau

skas

in W

estla

nd, M

ichi

gan

from

a p

umpk

in p

atch

that

w

as c

ompo

sted

with

gra

ss c

lippi

ngs

Circ

ular

cle

ar p

laqu

es, 0

.5m

m d

iam

eter

at 4

8 ho

urs

on M

. sm

egm

atis

ho

st a

t 32°

C

Sip

hovi

ridae

Stru

ctur

e

70,1

83 b

ase

pairs

, Lin

ear G

enom

e w

ith 1

0 bp

3’ o

verh

ang,

TC

GA

TCA

GC

C

58.2

% G

C,1

19 p

rote

in c

odin

g ge

nes,

13

tRN

A g

enes

Pia

tt

Dev

era

Cas

eJul

es

Jarv

iP

hara

oh

Arm

adill

o

Figu

re 1

- Tr

ansm

issi

on E

lect

ron

Mic

rosc

opy

Imag

es (D

isco

vere

d 20

15-2

016)

Figu

re 2

- A

ligne

d G

enom

e M

aps

of

Rep

rese

ntat

ive

Phag

es D

epic

ting

Leve

l of

Sim

ilarit

y be

twee

n G

enom

es U

sing

Ph

amer

ator

(Lef

t and

bot

tom

)

Top:

Pha

ge G

uuel

aD fr

om c

lust

er L

2 M

iddl

e: B

rom

den

draf

t fro

m c

lust

er L

4 B

otto

m: D

yoE

dafo

s dr

aft f

rom

clu

ster

L4

Bro

mde

n is

clo

sely

alig

ned

with

bot

h ph

ages

. Pur

ple

colo

r ind

icat

es c

lose

al

ignm

ent.

Bro

mde

n ha

s a

shor

ter g

enom

e th

an b

oth

Guu

elaD

and

Dyo

Eda

fos

(left)

. B

rom

den

has

a sh

orte

r gen

ome

com

pare

d to

the

aver

age

geno

me

leng

th o

f L p

hage

s.

Bro

mde

n’s

com

plet

e ge

nom

e is

sho

wn

belo

w.

Hol

in P

rote

in in

Bro

mde

n A

hol

in is

a p

rote

in th

at fu

nctio

ns to

cre

ate

a “h

ole”

in th

e m

embr

ane

of th

e ho

st c

ell.

This

allo

ws

the

new

ly p

rodu

ced

phag

e to

be

rele

ased

at t

he e

nd o

f the

lytic

cyc

le. O

ne c

ompo

nent

cod

ed fo

r by

a ho

lin g

ene

is a

tran

smem

bran

e do

mai

n, w

hich

allo

ws

the

holin

to a

ttach

to a

spe

cific

are

a in

the

mem

bran

e an

d is

nee

ded

for a

hol

in to

func

tion.

The

re a

re tw

o ge

nes

in B

rom

den

that

cou

ld h

ave

a po

tent

ial h

olin

func

tion,

gp2

8 an

d gp

29, a

ccor

ding

to th

eir l

ocat

ion

and

com

paris

on to

oth

er p

hage

gen

es.

How

ever

, it i

s ha

rd to

det

erm

ine

whi

ch g

ene

is a

hol

in o

r if b

oth

gene

s w

ork

toge

ther

, with

out s

peci

fic la

b da

ta.

Gp2

8:

●15

1 am

ino

acid

s ●

Pha

mily

193

0●

App

letre

e2_2

7, G

uuel

aD_2

9, M

iley1

6_29

, Nic

hola

sp3_

29, W

inky

_29

are

in P

ham

illy

1930

and

hav

e a

holin

func

tion

●0

trans

mem

bran

e do

mai

ns (h

ttp://

ww

w.e

nzim

.hu/

hmm

top/

serv

er/h

mm

top)

G

p29:

109

amin

o ac

ids

●P

ham

ily 3

7230

●R

umpe

lstil

tski

n_30

, Joe

Dirt

_28,

Loa

drie

_30

are

in P

ham

ily 3

7230

and

hav

e a

holin

func

tion

●3

trans

mem

bran

e do

mai

ns (h

ttp://

ww

w.e

nzim

.hu/

hmm

top/

serv

er/h

mm

top)

VI.S

peci

fic P

rote

in F

unct

ions

Tape

Mea

sure

Pro

tein

(TM

P) in

Bro

mde

n ●

Pro

tein

that

pro

vide

s in

form

atio

n an

d al

low

s m

ycob

acte

rioph

ages

to tr

ansp

ort

info

rmat

ion

into

the

host

cel

l dur

ing

an in

fect

ion

phas

e●

The

stud

y of

dom

ains

requ

ired

for t

he p

rote

in’s

func

tion

can

lead

to n

ew

disc

over

ies

in th

e ev

olut

ion

of m

ycob

acte

rioph

ages

Bro

mde

n’s

TMP

has

two

dom

ains

- see

figu

re 7

to th

e rig

ht fo

r an

exam

ple

●A

naly

zing

the

dom

ains

can

lead

to a

bet

ter u

nder

stan

ding

of t

he ta

pe

mea

sure

pro

tein

of B

rom

den

●Is

the

long

est g

ene

reco

rded

in B

rom

den

at 1

697

amin

o ac

ids

●S

urro

unde

d by

tail

asse

mbl

y ch

aper

ones

and

min

or ta

il pr

otei

ns

Figu

re 4

- Pl

aque

M

orph

olog

yA

fter c

ontin

uing

to p

ick

plaq

ues

from

dire

ct

plat

ing

tech

niqu

es,

Bro

mde

n’s

plaq

ues

wer

e co

nsis

tent

ly

circ

ular

, cle

ar a

nd

0.5m

m in

dia

met

er.

Con

sist

ent m

orph

olog

y pr

oves

it w

as a

pur

e st

ock.

Figu

re 5

- C

odon

Usa

ge B

ias

Com

paris

on (L

eft)

Whe

n co

mpa

ring

the

codo

n us

age

bias

of M

. sm

egm

atis

to th

e co

don

usag

e bi

as o

f Bro

mde

n as

soci

ated

w

ith e

ncod

ed tR

NA

s, w

e fo

und

that

m

any

tRN

A e

ncod

ed c

odon

s w

ere

mor

e fre

quen

tly u

sed

in B

rom

den,

pe

rhap

s ex

plai

ning

the

reas

on fo

r en

code

d tR

NA

s.

Figu

re 3

- Ly

sin

and

Hol

in G

enes

(Top

and

rig

ht)

Bro

mde

n gp

28 a

nd g

p29

(circ

led

in b

lue)

are

lo

cate

d do

wns

tream

of L

ysin

A a

nd L

ysin

B

(bot

h ci

rcle

d in

red)

. The

hol

in g

ene

is

com

mon

ly fo

und

dow

nstre

am b

ecau

se a

ll th

ree

prot

eins

are

use

d in

the

lysi

s m

odul

e.

The

imag

e on

the

right

sho

ws

the

lysi

s pr

oces

s w

ith th

e gr

een

figur

es a

ctin

g as

the

lysi

n pr

otei

ns a

nd t

he b

lue

figur

es a

ctin

g as

th

e ho

lin p

rote

ins.

The

yel

low

and

pur

ple

figur

es re

pres

ent m

embr

anes

of t

he h

ost c

ell.

Th

e ho

lin a

llow

s fo

r the

lysi

n to

pas

s th

roug

h th

e ce

ll m

embr

ane

and

degr

ade

the

oute

r m

embr

ane

in o

rder

to re

leas

e ph

age

prog

eny.

Figu

re 7