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Mon, Wed 11:30 AM - 12:50, on Zoom*Prof: Gill BejeranoCA: Boyoung (Bo) Yoo* Track class on Piazza

CS273A

Gill Lecture 6: Repeats II

The Human GenomeSource Code

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Announcements

• Homework 3 is due 2/24 11:59PM PST

• Error in the homework 3 writeup– In Question 2.3, the line count we gave for hg19_lung_gtex.bed was not uniquely sorted. This file should be uniquely sorted and have 108,874 lines – Also, the overlapping regions (the result from bedtoolsintersect) should be uniquely sorted

• Reminder: midterm survey will close today at 5PM (anonymous!)

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TTATATTGAATTTTCAAAAATTCTTACTTTTTTTTTGGATGGACGCAAAGAAGTTTAATAATCATATTACATGGCATTACCACCATATACATATCCATATCTAATCTTACTTATATGTTGTGGAAATGTAAAGAGCCCCATTATCTTAGCCTAAAAAAACCTTCTCTTTGGAACTTTCAGTAATACGCTTAACTGCTCATTGCTATATTGAAGTACGGATTAGAAGCCGCCGAGCGGGCGACAGCCCTCCGACGGAAGACTCTCCTCCGTGCGTCCTCGTCTTCACCGGTCGCGTTCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAATAAAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATTGGCAGTAACCTGGCCCCACAAACCTTCAAATTAACGAATCAAATTAACAACCATAGGATGATAATGCGATTAGTTTTTTAGCCTTATTTCTGGGGTAATTAATCAGCGAAGCGATGATTTTTGATCTATTAACAGATATATAAATGGAAAAGCTGCATAACCACTTTAACTAATACTTTCAACATTTTCAGTTTGTATTACTTCTTATTCAAATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCTATACTTTAACGTCAAGGAGAAAAAACTATAATGACTAAATCTCATTCAGAAGAAGTGATTGTACCTGAGTTCAATTCTAGCGCAAAGGAATTACCAAGACCATTGGCCGAAAAGTGCCCGAGCATAATTAAGAAATTTATAAGCGCTTATGATGCTAAACCGGATTTTGTTGCTAGATCGCCTGGTAGAGTCAATCTAATTGGTGAACATATTGATTATTGTGACTTCTCGGTTTTACCTTTAGCTATTGATTTTGATATGCTTTGCGCCGTCAAAGTTTTGAACGATGAGATTTCAAGTCTTAAAGCTATATCAGAGGGCTAAGCATGTGTATTCTGAATCTTTAAGAGTCTTGAAGGCTGTGAAATTAATGACTACAGCGAGCTTTACTGCCGACGAAGACTTTTTCAAGCAATTTGGTGCCTTGATGAACGAGTCTCAAGCTTCTTGCGATAAACTTTACGAATGTTCTTGTCCAGAGATTGACAAAATTTGTTCCATTGCTTTGTCAAATGGATCATATGGTTCCCGTTTGACCGGAGCTGGCTGGGGTGGTTGTACTGTTCACTTGGTTCCAGGGGGCCCAAATGGCAACATAGAAAAGGTAAAAGAAGCCCTTGCCAATGAGTTCTACAAGGTCAAGTACCCTAAGATCACTGATGCTGAGCTAGAAAATGCTATCATCGTCTCTAAACCAGCATTGGGCAGCTGTCTATATGAATTAGTCAAGTATACTTCTTTTTTTTACTTTGTTCAGAACAACTTCTCATTTTTTTCTACTCATAACTTTAGCATCACAAAATACGCAATAATAACGAGTAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTTTCCTACGCATAATAAGAATAGGAGGGAATATCAAGCCAGACAATCTATCATTACATTTAAGCGGCTCTTCAAAAAGATTGAACTCTCGCCAACTTATGGAATCTTCCAATGAGACCTTTGCGCCAAATAATGTGGATTTGGAAAAAGAGTATAAGTCATCTCAGAGTAATATAACTACCGAAGTTTATGAGGCATCGAGCTTTGAAGAAAAAGTAAGCTCAGAAAAACCTCAATACAGCTCATTCTGGAAGAAAATCTATTATGAATATGTGGTCGTTGACAAATCAATCTTGGGTGTTTCTATTCTGGATTCATTTATGTACAACCAGGACTTGAAGCCCGTCGAAAAAGAAAGGCGGGTTTGGTCCTGGTACAATTATTGTTACTTCTGGCTTGCTGAATGTTTCAATATCAACACTTGGCAAATTGCAGCTACAGGTCTACAACTGGGTCTAAATTGGTGGCAGTGTTGGATAACAATTTGGATTGGGTACGGTTTCGTTGGTGCTTTTGTTGTTTTGGCCTCTAGAGTTGGATCTGCTTATCATTTGTCATTCCCTATATCATCTAGAGCATCATTCGGTATTTTCTTCTCTTTATGGCCCGTTATTAACAGAGTCGTCATGGCCATCGTTTGGTATAGTGTCCAAGCTTATATTGCGGCAACTCCCGTATCATTAATGCTGAAATCTATCTTTGGAAAAGATTTACAATGATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATAAAG

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Class Topics(0) Genome context:

cells, DNA, central dogma(1) Genome content / genome function:

genes, gene regulation, epigenetics, repeats, SARS-CoV-2(2) Genome sequencing:

technologies, assembly/analysis, technology dependence (3) Genome evolution:

evolution = mutation + selection, main forces of evolution:Neutral evolution, Negative selection, Positive selection

(4) Population genomics:Human migration, paternity testing, forensics, cryptogenomics

(5) Genomics of human disease:personal genomics, GxE disease types, deep dive monogenics

(6) Comparative Genomics :Genomics of amazing animal adaptations, ultraconservation

good morning!

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We are technically DONE with genome function

Biology – not that complicated!!

Functional part list • In our genome:

• Gene• Protein coding• Non coding / RNA genes

• Gene regulatory elements• “Atomic” event: transcription factor binding site• Build up: promoters, enhancers, silencers, gene reg. domain

• “Around” our genome• Chromatin – open / closed• Epigenomic (and some epigenetic) marks

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The Functional Genome

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Type # in genome % of genomegenes 20,000 2-3%

ncRNA 20,000+ 2%

cis elements 1,000,000 10-15%

Corollary: most of the genome is devoid of function (which we understand)

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Classes of Interspersed Repeats

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LINE & SINE Elements

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LINE & SINE Elements

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SARS-CoV-2 integration into human genome?

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2020

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Typical RT work…

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Genomic Transmission

For repeat copies to accumulate through human generations they must make it into the germline cells (eggs & sperms).

Equally true for any genomic mutation.

cell

genome =all DNA

chicken ≈ 1013 copies(DNA) of egg (DNA)

chicken

eggegg

egg

celldivision

DNA strings =Chromosomes

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DNA Transposons

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Retrovirus-like Elements

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Every Genome is DifferentDNA Replication is imperfect – between individuals of the same species, even between the cells of an individual.

...ACGTACGACTGACTAGCATCGACTACGA...

chicken

egg ...ACGTACGACTGACTAGCATCGACTACGA...

functionaljunk

TT CAT

“anythinggoes”

many changesare not tolerated

chicken

This has bad implications – disease, and good implications – adaptation.

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TE composition and assortment vary among eukaryotic genomes

20%

40%

60%

80%

100%

Slime

mol

dBud

ding

yea

stFi

ssio

n ye

ast

Neuro

spor

aAra

bido

psis

RiceNem

atod

eDro

soph

ila

Mos

quito

Fugu

Mou

seHum

an

DNA transposons

LTR Retro.

Non-LTR Retro.

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Repeats: mostly neutralMost repeat events/instances are neutral.

Ie, a repeat instance is dropped in a new place, and joins the rest of the neutral DNA, gradually decaying over time.

Many repeat copies are “dead as a duck” on arrival at their new location (eg 5’ truncation).

Some instances may be active (spawn new instances) for a while, but when an active copy is hit by a mutation – the host is not affected, the instance is inactivated and decays away.

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Repeat Ages

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Figure from Ryan Gregory (2005)

INTERSPECIES VARIATION IN GENOME SIZE WITHIN VARIOUS GROUPS OF ORGANISMS

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The amount of TE correlate positively with genome size

Plas

mod

ium

Slim

e m

old

Budd

ing

yeas

t

Fiss

ion

yeas

t

Neur

ospo

ra

Arab

idop

sis

Bras

sica

Rice

Mai

zeNe

mat

ode

Dros

ophi

laM

osqu

itoSe

a sq

uirt

Zebr

afis

hFu

guM

ouse

Hum

an

0

500

1000

1500

2000

2500

3000 Genomic DNA

TE DNA

Protein-codingDNA

Mb

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TEs

Protein-coding genes

The proportion of protein-coding genes decreases with genome size, while the proportion of TEs increases with genome size

Gregory, Nat Rev Genet 2005 21

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Repeats: not just neutralSo far we treated all repeat proliferation events as neutral.

While the majority of them appear to be neutral, this is certainly not the case for all repeat instances.

And because there are so many repeat instances even a small fraction of all repeats can be a big set compared to other types of elements in the genome.(Eg, 1% of ½ the genome is still a lot)

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Repeats & Retroposed Genes

Remember how LINEs reverse transcribe copies of themselves back into the genome? How they sometimes reverse transcribe SINEs “by mistake”? Well, they also grab m/ncRNAs and reverse transcribe them into the genome!

Retrogenes (“retrotranscribed”):Protein coding RNA that was reverse transcribed and inserted back into the genome.The RNA can be grabbed at any stage (partial/full transcript, before/during/after all introns are spliced).

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Retroposed Genes & Pseudogenes

Pseudogenes (“dead genes”):Genomic sequences that resemble (originated from) genes that no longer make proteins.

Retrogenes (“retrotranscribed”):Protein coding RNA that was reverse transcribed and inserted back into the genome.The RNA can be grabbed at any stage (partial/full transcript, before/during/after all introns are spliced).

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Repeat Insertions Can “Break Things”

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Repeat Insertions Can “Make Things”

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Any Sequence Can Become Functional

Random mutation (especially in a large place like our genome) can create functional DNA elements out of neutrally evolving sequences.

So is there anything special about a piece of DNA from a repetitive origin that takes on a new function?

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Regulatory elements from obile Elements

[Yass is a small town in New South Wales, Australia.]

Co-option event, probably due to favorable genomic context

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Origins, Current Function, Cooption

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Britten & Davidson Hypothesis: Repeat to Rewire!

Enhancer structure reminder

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The Road to Co-Option

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Transposition Event

Random Mutations

Neutral decay

PotentialCo-OptionStates

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Assemby Challenges

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Inferring Phylogeny Using Repeats

[Nishihara et al, 2006]

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Transposons as Genetics Engineering Tools

Human Gene Therapy

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Repeats: fun conspiracy theories1. Repeats wreck so much havoc in the genome, by inserting themselves, deleting segments between instances and more – they make the genome feel like a “rolling sea”. Maybe it is because of them that enhancers evolved to work irrespective of distance and orientation?

2. When the last active copy of a repeat dies, all instances of the repeat are now decaying. Wait long enough and they lose resemblance to each other. Look in 200My and you never know they belonged to the same repeat family. So… if half the genome is recognizable as repetitive now, how much of the genome originated from repeats? Most of it?

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Repeats: fun conspiracy theories3. If repeats do significantly accelerate the rate of creation of novel functional (gene/regulation) elements – how many functional elements today came from repeats (including old ones we no longer can recognize as such)? Most?

4. Is that why our genome “tolerates” these elements?

5. You make a conspiracy theory…

6. You think of ways* to solve one!

* Computationally. Evolution is mostly computational business.

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II. Simple Repeats

•Every possible motif of mono-, di, tri- and tetranucleotide repeats is vastly overrepresented in the human genome.

•These are called microsatellites,Longer repeating units are called minisatellites,The real long ones are called satellites.

•Highly polymorphic in the human population.•Highly heterozygous in a single individual.•As a result microsatellites are used in paternity testing, forensics, and the inference of demographic processes.

•There is no clear definition of how many repetitions make a simple repeat, nor how imperfect the different copies can be.

•Highly variable between species: e.g., using the same search criteria the mouse & rat genomes have 2-3 times more microsatellites than the human genome. They’re also longer in mouse & rat.

AAAAAAAAA

CACACACAC

CAACAACAA

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DNA Replication

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Simple Repeats Create Funky DNA structures

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These Bumps Give The DNA Polymerase Hiccups

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Expandable Repeats and Disease

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Restriction Enzymes• Restriction enzymes recognize and make a cut within

specific DNA sequences, known as restriction sites. • This is usually a 4-6 base pair palindromic sequence.• Naturally found in different types of bacteria• Bacteria use restriction enzymes to protect themselves

from foreign DNA • Many have been isolated and sold for use in lab work

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blunt end

sticky end

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DNA Fingerprint BasicsDNA fragments of different size will be produced by a restriction enzyme that cuts at the points shown by the arrows.

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DNA fragments are then separated based on size using gel electrophoresis.

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DNA Fingerprinting can be used in paternity testing or murder cases.

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There are Tracks for it

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Interspersed vs. Simple RepeatsFrom an evolutionary point of view transposons and simple repeats are very different.

Different instances of the same transposon share common ancestry (but not necessarily a direct common progenitor).

Different instances of the same simple repeat most often do not.

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Now you really know most everythingIn the Genome:Genes (up to 5% of genome)

coding and non coding (exons, introns)Gene regulation (15% of genome)

proteins: transcription factors, chromatin remodelers, ...RNA genes: microRNAs, antisense, guide RNAs…DNA elements: TF binding sites, promoters, enhancers, ...

Repetitive sequences (50% of genome)Interspersed repeats (transposons that hop around)Simple repeats (local replication “sore spots”)

Categories are not mutually exclusive.Function comes & goes with evolution = mutation + selection

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Class Topics(0) Genome context:

cells, DNA, central dogma(1) Genome content / genome function:

genes, gene regulation, epigenetics, repeats, SARS-CoV-2(2) Genome sequencing:

technologies, assembly/analysis, technology dependence(3) Genome evolution:

evolution = mutation + selection, main forces of evolution:Neutral evolution, Negative selection, Positive selection

(4) Population genomics:Human migration, paternity testing, forensics, cryptogenomics

(5) Genomics of human disease:personal genomics, GxE disease types, deep dive monogenics

(6) Comparative Genomics :Genomics of amazing animal adaptations, ultraconservation

good day!

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TTATATTGAATTTTCAAAAATTCTTACTTTTTTTTTGGATGGACGCAAAGAAGTTTAATAATCATATTACATGGCATTACCACCATATACATATCCATATCTAATCTTACTTATATGTTGTGGAAATGTAAAGAGCCCCATTATCTTAGCCTAAAAAAACCTTCTCTTTGGAACTTTCAGTAATACGCTTAACTGCTCATTGCTATATTGAAGTACGGATTAGAAGCCGCCGAGCGGGCGACAGCCCTCCGACGGAAGACTCTCCTCCGTGCGTCCTCGTCTTCACCGGTCGCGTTCCTGAAACGCAGATGTGCCTCGCGCCGCACTGCTCCGAACAATAAAGATTCTACAATACTAGCTTTTATGGTTATGAAGAGGAAAAATTGGCAGTAACCTGGCCCCACAAACCTTCAAATTAACGAATCAAATTAACAACCATAGGATGATAATGCGATTAGTTTTTTAGCCTTATTTCTGGGGTAATTAATCAGCGAAGCGATGATTTTTGATCTATTAACAGATATATAAATGGAAAAGCTGCATAACCACTTTAACTAATACTTTCAACATTTTCAGTTTGTATTACTTCTTATTCAAATGTCATAAAAGTATCAACAAAAAATTGTTAATATACCTCTATACTTTAACGTCAAGGAGAAAAAACTATAATGACTAAATCTCATTCAGAAGAAGTGATTGTACCTGAGTTCAATTCTAGCGCAAAGGAATTACCAAGACCATTGGCCGAAAAGTGCCCGAGCATAATTAAGAAATTTATAAGCGCTTATGATGCTAAACCGGATTTTGTTGCTAGATCGCCTGGTAGAGTCAATCTAATTGGTGAACATATTGATTATTGTGACTTCTCGGTTTTACCTTTAGCTATTGATTTTGATATGCTTTGCGCCGTCAAAGTTTTGAACGATGAGATTTCAAGTCTTAAAGCTATATCAGAGGGCTAAGCATGTGTATTCTGAATCTTTAAGAGTCTTGAAGGCTGTGAAATTAATGACTACAGCGAGCTTTACTGCCGACGAAGACTTTTTCAAGCAATTTGGTGCCTTGATGAACGAGTCTCAAGCTTCTTGCGATAAACTTTACGAATGTTCTTGTCCAGAGATTGACAAAATTTGTTCCATTGCTTTGTCAAATGGATCATATGGTTCCCGTTTGACCGGAGCTGGCTGGGGTGGTTGTACTGTTCACTTGGTTCCAGGGGGCCCAAATGGCAACATAGAAAAGGTAAAAGAAGCCCTTGCCAATGAGTTCTACAAGGTCAAGTACCCTAAGATCACTGATGCTGAGCTAGAAAATGCTATCATCGTCTCTAAACCAGCATTGGGCAGCTGTCTATATGAATTAGTCAAGTATACTTCTTTTTTTTACTTTGTTCAGAACAACTTCTCATTTTTTTCTACTCATAACTTTAGCATCACAAAATACGCAATAATAACGAGTAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTTTCCTACGCATAATAAGAATAGGAGGGAATATCAAGCCAGACAATCTATCATTACATTTAAGCGGCTCTTCAAAAAGATTGAACTCTCGCCAACTTATGGAATCTTCCAATGAGACCTTTGCGCCAAATAATGTGGATTTGGAAAAAGAGTATAAGTCATCTCAGAGTAATATAACTACCGAAGTTTATGAGGCATCGAGCTTTGAAGAAAAAGTAAGCTCAGAAAAACCTCAATACAGCTCATTCTGGAAGAAAATCTATTATGAATATGTGGTCGTTGACAAATCAATCTTGGGTGTTTCTATTCTGGATTCATTTATGTACAACCAGGACTTGAAGCCCGTCGAAAAAGAAAGGCGGGTTTGGTCCTGGTACAATTATTGTTACTTCTGGCTTGCTGAATGTTTCAATATCAACACTTGGCAAATTGCAGCTACAGGTCTACAACTGGGTCTAAATTGGTGGCAGTGTTGGATAACAATTTGGATTGGGTACGGTTTCGTTGGTGCTTTTGTTGTTTTGGCCTCTAGAGTTGGATCTGCTTATCATTTGTCATTCCCTATATCATCTAGAGCATCATTCGGTATTTTCTTCTCTTTATGGCCCGTTATTAACAGAGTCGTCATGGCCATCGTTTGGTATAGTGTCCAAGCTTATATTGCGGCAACTCCCGTATCATTAATGCTGAAATCTATCTTTGGAAAAGATTTACAATGATTGTACGTGGGGCAGTTGACGTCTTATCATATGTCAAAGTCATTTGCGAAGTTCTTGGCAAGTTGCCAACTGACGAGATGCAGTAACACTTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCACAAACTTTAAAACACAGGGACAAAATTCTTGATATGCTTTCAACCGCTGCGTTTTGGATACCTATTCTTGACATGATATGACTACCATTTTGTTATTGTTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATGTTTTCAATGTAAGAGATTTCGATTATCTTATAGTTCATACATGCTTCAACTACTTAATAAATGATTGTATGATAATAAAG

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Human Genome Project

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1990: Start

2001: Draft

2003:“Finished” (really 50 years to W&C)$3 billion dollar

3 billion basepairs

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DNA Sequencing: Plummeting Costs

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100 million species

7 billion individuals

1013 cells in a human

We could never sequence enough

or sequence just an active portion

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DNA Sequencers: Room-size to USB-size

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Illumina HiSeqX

PacBio RS II Oxford Nanopore MinIon

ABI 3730xl

1st gen

3rd gen

2nd gen

3rd gen

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