INTRODUCTION TO GENOMES

Cells are the fundamental units of life. All living cells are built from CELLS: small,
membrane-enclosed units filled with a concentrated aqueous solution of chemicals
and endowed with the extraordinary ability to create copies of themselves by growing
and the dividing in two.
But cells are not alike, they can be wildly different. They vary enormously in size and
shape and are diverse in their chemical requirements. They also reflect differences in
CELL FUNCTION (factories of production, engines, electricity generators…)
But although the cells of all living things are infinitely varied when viewed from the
outside, they are fundamentally similar inside.

Cells have a similar Basic Chemistry

Molecular biology: all cells are composed of the same sorts of molecules that
participate in the same type of chemical reactions.
Cells are commonly specialized to an extreme degree for particular tasks and leaving
them dependant on their fellow cells (basic requirement)
In what sense all living cells are alike?
In all organisms, genetic information is carried in DNA molecules.
The information is written in the same chemical code (four nucleotides).
It is interpreted by the same chemical machinery.
Constructed out of the same building blocks
Replicated in the same way
Display homeostasis, reproduce themselves, grow… Highly ordered!

CENTRAL DOGMA

In all living cells information flows form DNA to RNA

(transcription) and form RNA to protein (translation).
Together this processes are known as gene expression.

Behaviour and appearance are dictated by proteins.

Same Ancestral Cell

All present-Day Cells have apparently evolved from the Same Ancestor
DNA replication + random mutations + selection
Daughter cells resemble the parent cell but the copy is not always perfect. The
differences are due to random mutations.
Mutations can be for the worse (less able to survive), for the better or neutral.
The genes of the next generations will be the genes of the survivors. (Natural
selection)
BASIS OF EVOLUTION: process by which living species become gradually modified and
adapted to their environment in more and more sophisticated ways.
This explains why present-day cells are so similar in their fundamentals: they have all
inherited their genetic instructions form the same common ancestor.
Common ancestor: 3.5 and 3.8 billion year ago.

Through a very long process of mutations and natural selection, the descendants of
this ancestral cell have gradually diverged to fill every habitat on Earth with organisms
that exploit the potential of the machinery in an endless variety of ways.

Genes Provide the Instructions for Cellular Form, Function, and

Complex Behaviour
• A cell’s genome (entire sequence of nucleotides) provides a genetic program that
instructs the cell how to behave and how to grow into an organism.
•Differentiated cell types are generated during embryonic development form a single
fertilized egg cell (cell differentiation) and all contain the complete genome of the species
(identical copies of the DNA of the species).
•Different cells express different genes, depending on their needs and the cues that they
receive from their surroundings (differential gene expression). That is, they use their
genes to produce some proteins and not others.

Organisms vary enormously in the size of their genomes:

Genome size is measured in

nucleotide pairs of DNA per
haploid genome (per single
copy). Closely related
organisms can vary widely in
the quantity of DNA in their
genomes (length of green bars),
even though they contain
similar numbers of functionally
distinct genes.
Human Genome Organization
Integenic DNA: noncoding DNA. Stretch of
DNA sequences located between genes.
Genes provide the instructions for:
-Cellular form.
-Function.
-Complex behaviour.
More complexity  more different genes
GENOME EVOLUTION

At DNA level, evolution is slow

• Human – Human: 99.9% homology
• Human – Chimp: 99%
• Human – Orangutan: 98 %
•Mycoplasma genitalium: 468 genes (582,970 bp), the smallest known in a
free-living organism.
•Minimal Genome Project: 382 genes: Already synthetized
Is this the chassis to design new organisms with predetermined functions, e.g. H2 /
octane production? Craig Venter Synthetic Biology
Craig Venter and his team have built the genome of a bacterium from scratch (de
materias primas) and incorporated it into a cell to make what they call the world's first
synthetic life form.

Some Genes Evolve Rapidly, Others Are Highly Conserved

Depending on their function (critical or not), some parts of the genome change more
easily than others in the course of evolution.
In spite the evolutionary history, a number of (very important) genes remain
conserved in all living organisms.
The classification of the living world into the
three domains is based on the 16S ribosomal
RNA sequence.

16 S ribosomal RNA is a
component of the 30S small Genetic information conservation along evolution.
subunit of prokaryotic ribosomes.
The Tree of Life Has Three primary Branches: Bacteria, Archaea,
and Eukaryotes
Nowadays, the complete DNA sequence of an organism defines the species with almost
perfect precision and in exhaustive detail.
The number of differences between the DNA sequences of two organisms can be used to
provide a direct, objective, quantitative indication of the evolutionary distance between
them.

Based on the sequence of 16/18S rRna

Each branch on the tree is labelled with the name of a representative member of that
group, and the length of each brach corresponds to the degree of difference in their
small subunit rRNA sequences.
To construct such a tree, biologist have focused on one particular gene that is
conserved in all living species: the gene that codes for one of the ribosomal RNAs of
the small ribosomal subunit. THIS COMPONENT HAS BEEN WELL CONSERVED SINCE
EARLY IN THE HISTORY OF LIFE ON EARTH.

Will we be able to predict natural evolution? (OPINION)

Some genomes have been completely sequenced. Genome sized and gene number
vary between strains of a single species, especially for bacteria and archaea. For
Eukaryotes, many genes can give rise to several alternative variant proteins, so that
the total number of proteins specified by the genome is substantially greater than the
number of genes.  Genes work interacting one each other, we are combinations of
genes.
More than 3800 organisms have had their genomes sequenced.

New Genes Are Generated from Preexisting Genes

Intragenic mutation: consists on the modification, deletion or duplication of one or
more nucleotides in the gene’s DNA sequence that are a result of rare mistakes during
DNA replication or DNA repairing.
Gene Duplication: consists on the duplication of a gene, a larger segment of DNA or
even the whole genome, creating a set of closely related genes within a single cell,
which is known as gene families. When divisions progressively occur to the cell
progeny, these duplicated genes can undergo additional mutations and assume
different functions from the
original ones.

DNA segment shuffling: consists in

the breakage and rejoining of two
or more separated existing genes
or DNA sequences producing a
hybrid gene.

Horizontal transfer: consists on the

transference of a piece of DNA
from the genome of one cell to that
of another, even among species.
Rare among eukaryotes but
common among prokaryotes.

Homologous, Paralogs and Orthologous genes

Orthologs are genes in different species that evolved from a common ancestral gene
by speciation. Normally, orthologs retain the same function in the course of evolution.
Identification of orthologs is critical for reliable prediction of gene function in newly
sequenced genomes.
Paralogs are genes related by duplication within a genome. Orthologs retain the same
function in the course of evolution, whereas paralogs evolve new functions, even if
these are related to the original one.
Homologous gene: is a gene related to a second gene by descent from a common
ancestral DNA sequence.

Speciation is the
origin of a new
specie capable of
making a living in a
new way from the
species from which
it arose. As part of
this process it has
also acquired some
barrier to genetic
exchange with the
parent species.
New genes can appear by other mechanisms. Sometimes some genes appear and they
have no ancestor ones  This are orphan genes.

Gene Duplications Give Rise to Families of Related Genes within

a Single Cell
Each family comes from an ancestor gene.
Gene families are variants of homologous genes. Only single copies 50%
The function of a gene can often be deduced from Gene families 50%
its sequence.

Once the sequence of a newly discovered genes has been determined, it is possible, by
bioinformatics tools, to search very complex databases for genes related to it.
The function of the new gene is likely to be similar to that of the already-known
homologs.
More than 200 gene families are common to all three primary branches of the tree of
life.
76 are truly ubiquitous (in all analysed genomes).The majority include proteins of the
translation and transcription systems.

Mutations Reveal the Functions of Genes

The analysis of gene functions depends on two

complementary approaches: genetics and biochemistry.

A mutant phenotype reflecting the function of a gene. A normal yeast

(left) is compared with a mutant (right) in which a change in a single gene
has changed its shape.