INF 5010 Introduction to biology Ole Christian Lingjærde Division for Biomedical Informatics Dept of Computer Science, UiO

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What is life? Biology is the study of living organisms, where the latter may be defined as: A naturally occurring protein based entity, able to make a complete copy of itself, using only its own machinery In practice, the only known examples of such entities are DNA based.

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The variety of life forms

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Important terms

Archaea, Bacteria, Eukaryota: The three branches of living organisms

Prokarytoa: Joint term for archaea and bacteria. All prokaryota are unicellular organisms and lack a membrane-bound nucleus.

Eukaryota: May be unicellular or multicellular and all have a nucleus and other membrane-enclosed organelles

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Important terms

Opisthokonta: Large group of eukaryotes which includes fungi, choanoflagellates* and animals.

* free-living unicellular and colonial flagellate eukaryotes considered to be the closest living relatives of the animals

Metazoa: This is a different name for animals

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Finding Homo sapiens

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All l

ivin

g or

gani

sms

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Euka

ryot

es

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Anim

als

Bilateria = animals with bilateral symmetry, i.e. both a front and a back, as well as an upside and downside

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Bila

teria

Deuterostomia = subclass of animals with a particular embryonic development (the first opening becomes the anus, while in the other branches it becomes the mouth)

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Deu

tero

stom

ia

Chordata = subclass of deuterostomia where embryos possess among other things a primitive axis ("backbone") called a notochord and a tail.

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Cho

rdat

a

Craniata = chordates with skulls (i.e. heads containing brain and sense organs)

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Cra

niat

a

Vertebrata = chordates with backbones

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Verte

brat

a

Gnathostomata = jawed vertebrates

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Gna

thos

tom

ata

Sarcopterygii = "lobe-finned fish" includes the tetrapods (these branches split paths around 395 million years ago)

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Sacr

opte

rygi

i

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Terr

estri

al v

erte

brat

es

Amniota = group of tetrapods (four-limbed vertebrates) with eggs that are adapted to be laid on land (rather than in water).

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Amni

ota

Synapsida = amniota with an opening low in the skull roof behind each eye.

How many species? “If we say 400,000, we shall, perhaps, not be very wide of the truth” John Obadiah Westwood (1833)

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"It is [...] interesting that the total number of species obtained by extrapolating down to around 1mm or so is in the range 10 million to 50 million." Robert May (1988)

Log10(length in mm)

Num

ber o

f spe

cies

𝑆𝑆 ~

1 𝐿𝐿2

Why so many species?

"Life finds a way." Jeff Goldblum (Jurassic Park, 1993)

Life is

• A dynamic entity • Molded by evolutionary forces • Filling niches as they become available • Subject to a constantly changing environment

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DNA: the common thread "DNA is the common thread that links every living thing with a single primaeval ancestor." John Sulston

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DNA: the common thread

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The DNA molecule consists of two parallel strands attached to each other by hydrogen bonds. Each strand consists of a backbone and bases attached to the backbone. The information in DNA is contained in the order of the bases (of which there are four types) along the strands.

A more detailed view

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Base pairing rule:

G on one strand is always attached to C on the other.

A on one strand is always attached to T on the other.

Each strand thus contains all the information.

Nucleotides The basic building blocks of DNA molecules are called nucleotides, each consisting of • a sugar (dexoyribose) • a phosphate group • a base (A, C, G or T)

RNA are molecules closely related to DNA: • a sugar (ribose) • a phosphate group • a base (A, C, G or U)

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The DNA double helix It was in 1953 that the double-helical structure of DNA was proposed by James Watson and Francis Crick.

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"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetical material."

DNA replication

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Original DNA First replication Second replication

This process is referred to as semiconservative replication, since each of the two copies consist of one original DNA strand and one new copy.

Errors in DNA replication DNA replication is not completely faultless.

While the fidelity of the copying process is generally high, the large number of nucleotides in a DNA molecule means that errors do happen.

Some types of replication errors are: • mispairings • insertions and deletions

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Mispairings caused by a slight shift in position of one strand

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A nucleotide is wrongly paired with another (e.g. T-G), causing an inconsistency between the two strands.

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Insertions and deletions caused by strand slippage

One strand has a nucleotide that is not paired at all with a nucleotide on the other strand, causing an insertion (left branch) or a deletion (right branch) in the new strand.

Mutations Sophisticated DNA repair mechanisms in the cell fix most mistakes introduced in DNA replication.

Mistakes that evade repair, become permanent mutations. These will be present in all future generations of that particular cell lineage (unless mutated again).

Many types of mutations exist (some shown in figure).

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Substitution Insertion

Deletion Frameshift

Somatic vs. germ line Somatic mutations occur in nonreproductive cells and will not be passed onto offspring. Germ line mutations occur in reproductive cells (like egg and sperm) and will be passed onto offspring.

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What can mutations do? Mutations may have no effect, small effect or large effect.

Some mutations have no effect, unless specific conditions (e.g. the presence of other mutations) are also present.

Even a single mutation can cause alterations with widespread effect.

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Example: Flies carrying Hox mutations may sprout legs on their foreheads instead of antennae:

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Greaves and Maley, Nature (2012)

Example: Cancer involves an accumulation of somatic mutations, leading to uncontrolled proliferation. Each cancer is, in effect, multiple different (subclonal) cancers that occupy overlapping or distinct tissue habitats.

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Example: Mutations in bacterial genomes may lead to resistance to antibiotics. As for cancer, there is a selective pressure favoring those strains that are able to proliferate under the given restraints.

When mutations accumulate When a cell has accumulated a large number of mutations, or the DNA repair system is damaged by mutations, it can enter any of these states:

• an irreversible dormant stage (senescence) • programmed cell death (apoptosis) • unregulated proliferation (tumorigenesis)

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How common are mutations? • Mutation rates vary substantially among taxa,

and among different parts of the genome in a single organism.

• Mutation rates as low as 1 per billion (109) nucleotides and as high as 1 per 100 nucleotides have been reported.

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Example: • E. coli is a common gut bacterium • Genome size is about 4.2 million base pairs • Reported mutation rate is approx. 10-9

Each cell division thus leads to ~ 8.4 * 106 * 10-9 = 0.0084 new mutations.

Thus, approx. 1% of cells will contain a new mutation.

Since bacteria can divide as rapidly as every 30 mins, a single bacterium can grow into 1020 ~ 1 million cells in about 10 hours, so 10,000 bacteria will have accumulated at least one mutation (and not all the same!).

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Example:

• Several viruses have RNA genomes, including HIV, hepatitis C virus, and influenza.

• These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity.

• This diversity allows the population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs.

• This has lead to the concept of a quasispecies: a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population.

Ref: Lauring and Andino, Plos Pathogens, 2010.

Species vs. quasispecies

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Hostile environment

†

Not all mutations are bad!

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DNA packaging in the cell

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Ideograms

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Idiogram of Giemsa-stained chromosome 12.

The position of the centromere, which separates the two chromosome arms (designated p and q), is shown as hatched area. At this resolution, the long q arm of chromosome 12 can be subdivided into two main regions, which are designated 12q1 and 12q2. Region 12q1 can be further subdivided into five subregions, designated 12q11 through 12q15, each of which corresponds to a band detected by Giemsa staining.

12q1

12

q2

The human genome

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22 chromosome pairs + two sex chromosomes

Genes in DNA encode proteins

Ole Christian Lingjærde INF 3350

F1 & F2 - 2006 - 44

Genes

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A gene, or transcription unit, includes a promoter, an RNA-coding region, and a terminator.

Proteins

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The building blocks of proteins are amino acids. These are small organic molecules that consist of a central carbon atom linked to an amino group, a carboxyl group, a hydrogen atom, and a variable component called a side chain. There are 20 different amino acids.

References • Nature Education (http://www.nature.com/scitable)

• Page 21-23,25,27-29,31,33,41-46 • Tree of Life web project (http://tolweb.org/tree)

• Page 6-17 • Nature Reviews | Genetics

• Page 3,4,5 • Robert May (1988). How many species are there on earth?

Science, 241:1441-1449 • Page 18

• Understanding Evolution (http://evolution.berkeley.edu/) • Page 32,34

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