The document discusses several key topics related to molecular evolution and cell evolution: 1) All life on Earth descended from a single-celled common ancestor approximately 3.7 billion years ago. RNA may have functioned as the original self-replicating molecule before the emergence of DNA and proteins. 2) Mitochondria and chloroplasts likely originated through endosymbiotic relationships with bacteria, as evidenced by their retained genomes. 3) DNA and protein sequences can be compared to reconstruct evolutionary relationships and develop phylogenetic trees showing how groups of organisms are related. Slowly-evolving sequences like rRNA are used for distant comparisons, while rapidly-evolving mtDNA allows analysis of close relationships.

1. CELL Evolution
1

2. Molecular evolution
• All forms of life on earth are descendants of a single cell a
common ancestor that approximately 3.7 billion years ago.
• Polymerization of monomers into biological macromolecules
requires the removal of water. This may be done by mild heat,
clay minerals, or chemical condensing agents.
• Charles Darwin explained how biological evolution occurs
through a process of natural selection , which operates on
variant forms of inherited traits. The variant that provides the
highest degree of reproductive fitness is selected over many
generations to become the predominant form in the entire
population.
• The evolution of organismal complexity generally correlates
with an increase in genome size, which occurs through
repeated duplications. Some duplications result from
transpositions, while others arise from unequal crossing-over.2

3. RNA World hypothesis
• RNA can carry genetic information as well as catalyze chemical
reactions. These two properties have led scientists to speculate
that RNA may have predated the cell as the original
independent replicator, or proto-life-form.
• Ribozymes are enzymes made of RNA rather than protein.
Although few in number they do exist in modern living cells.
• The RNA World scenario proposes that the first cells had both
genes and enzymes made of RNA. Ribozymes are catalytic
RNAs, that is, RNA molecules that perform chemical reactions.
Examples of ribozymes include the ribosome, ribonuclease P,
self-splicing introns, and viroids.
• RNA was likely used to perform chemical reactions and store
genetic information.
• One drawback to this idea is that RNA is less stable than DNA,
although RNA is more easily made given the primordial soup.
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4. Evolutionary Impact on Nucleic Acids and Proteins
• The sequences of DNA and its encoded proteins will gradually
change over periods of time due to the accumulation of mutations.
• Amino acid seq. of different proteins evolve at very different rates.
• Effects of mutations range from those that are detrimental and
presumably selected against, to those that are neutral or
potentially beneficial.
• Since the origin of life, the nucleic acid has had plenty of time to
accumulate mutations.
• Mutations are the driving force for diversity and evolution, the
protein seq.is ultimately what matters the most. Mutations that give
rise to different coding seq., and different structures of the protein
have the potential to affect the function of that protein. Mutations
that do not change the function of the protein are more tolerated.
• Some evolutionary trees are constructed using protein sequences.
This only works correctly when the protein is found in all
organisms in the comparison. 4

5. Evolutionary Impact on Nucleic Acids and Proteins
• Duplication is a major mechanism for creating new genes. New
genes may also be created by mixing and shuffling segments of
pre-existing genes.
• During gene duplications, a segment of DNA carrying a gene or
several genes is duplicated and reinserted into the genome
somewhere else. This provides a copy that can be mutated and
altered without seriously risking the loss of function for the
original gene product.
• As mutations accumulate in the gene duplicate, the presence
of the mutations can alter the function such that it may still be
related to the original function, but perhaps is enhanced or
slightly different in some way.
• Additionally, new genes can be made by shuffling parts around
from existing genes. The DNA segments for each are fused
together to yield a new gene. 5

6. Evolutionary Relationships
• Archaea share prokaryotic cell structure with the Eubacteria,
they are more closely related to Eukaryotes genetically.
• Archaea and Eubacteria are both prokaryotic in structure.
Neither has membrane- bound organelles, the largest of which
is a nucleus. The nucleus is reserved for eukaryotic cells, which
include all of domain Eukarya.
• Other similarities between Archaea and Eubacteria include the
presence of a single circular chromosome and the method of
cell division is through binary fission.
• Certain sequences within the genomes showed that Archaea
are more closely related to the eukaryotes than to the bacteria.
Further comparing and contrasting the Archaea and Eubacteria
showed that Archaea do not contain peptidoglycan and they
have strange lipids in their cell membranes.
• Archaea are found in harsh environments, which means they
are well adapted to extremes. 6

7. Source of Mitochondria and Chloroplasts
• Mitochondria and chloroplasts of eukaryotic cells are derived
from symbiotic bacteria that gradually lost their independence.
• Mitochondria & chloroplasts still possess own small genomes.
• Eukaryotic cells contain membrane-bound organelles that serve
to compartmentalize many cellular functions. These membrane-
bound organelles include the nucleus, which is the largest, and
many other smaller organelles such as mitochondria and
chloroplasts.
• The mitochondria are used for production of the energy source
and chloroplasts are used in photosynthesis to harvest sunlight
energy and convert it into chemical energy.
• The symbiotic theory proposes that the origins of several
structures within the eukaryotic cell arose by symbiosis of
different lineages of smaller organisms.
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8. Source of Mitochondria and Chloroplasts
• Mitochondria are derived from aerobic, heterotrophic bacteria. Chloroplasts
likely arose from photosynthetic bacteria. In this hypothesis, these
prokaryotes took up residence inside the larger eukaryotic cell and conferred
an advantage to the larger cell.
• Mitochondria and chloroplasts still have their own genomes supports the
symbiotic theory. These genomes are both circular, small, and have lost
many of the genes needed to live free of their larger host cell. Many lost but
necessary genes were at some point transferred to the host cell’s
chromosome. Mitochondria and chloroplasts are inherited through maternal
lineages. Several protozoan lineages have arisen by engulfing other single-
celled algae and thus have chloroplasts acquired by what is known as
secondary endosymbiosis.
• Primary endosymbiosis refers to the original uptake of prokaryotes by the
early eukaryotic cell. This is in contrast to secondary endosymbiosis, in
which a eukaryotic cell already having a prokaryotic internal resident
undergoes yet another endosymbiotic event to engulf another free-living
prokaryote. Secondary endosymbiosis likely is responsible for some kinds of
algae having chloroplasts. 8

9. DNA Sequence Contribution to Biological Classification
• The ancestries and relationships of groups of organisms may be derived by
comparison of DNA sequences.
• Slowly-changing sequences, such as ribosomal RNA, are needed to
compare distantly-related organisms.
• Rapidly-changing sequences, such as mitochondrial DNA, are used to
compare closely-related organisms.
• Evolutionary trees can be constructed using DNA, RNA, and protein
sequencing data for those nucleic acids or proteins present in all of the
organisms being compared.
• The ribosomal RNA, rRNA, genes are conserved across the domains of life,
and therefore represent an excellent target for sequencing and then drawing
evolutionary comparisons. However, due to the slow mutation rate, rRNA
genes are best used to compare only distantly-related organisms.
• For more closely-related species, mitochondrial DNA sequences are used
due to their faster rates of mutations.
• It must be noted that base changes can revert, which represents a major
problem when comparing sequences.
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10. DNA Sequence Contribution to Biological Classification
• Mitochondrial DNA analysis implies that modern humans originated
in Africa about 100,000 years ago.
• Mitochondrial DNA changes extremely fast, particularly in the third
codon position and within intergenic regulatory regions. This makes
mitochondrial DNA exceptionally useful for studying evolutionary
relationships among closely-related species.
• In fact, sequence analysis of specific segments within mitochondrial
DNA allows researchers to distinguish between different racial
groups. Analysis of human mitochondrial sequences suggests that
humans originated from Africa approximately 100,000 years ago.
This analysis is further supported by examination of modern African
populations. Colonization of the continents likely started in Africa, but
branched into Euro-Asian tribes, who wandered through the Middle
East and into Europe about 40,000–50,000 years ago. American
Indians likely appeared in the Americas from Asia when a landbridge
was still present over the Bering Strait. The colonization of Oceania
is subject to much debate.
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11. DNA Sequence Contribution to Biological Classification
• DNA may be extracted from dead or extinct organisms and used to
reveal their relationships.
• DNA can be extracted from dead and extinct animals, sequenced,
and then used to draw conclusions about relationships among other
extinct animals or even some living animals. Mitochondrial DNA
analysis of frozen mammoths from Siberia indicates that only four to
five bases out of 350 differed between the mammoths and both
Indian and African elephants.
• Also, DNA can be extracted from fossils. This DNA can be further
analyzed to confirm evolutionary relationships.
• One myth, perhaps spurred by modern filmmakers, is that dinosaur
DNA can be extracted from mosquitos preserved in amber. Although
amber is a preservative of the insects, the DNA contained within the
mosquito is largely degraded.
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12. Sources of Change in Genomes
 Mutation
 Recombination
 Transposition
 Viruses: Retroviruses that have picked up host genes can make cells cancerous
 Gene Duplication occur from a rare recombination event between two
homologous chromosomes. Large amount of gene duplication occurred over
evolutionary time. There can be several genes belonging to the same family.
• Genes encoding new proteins can also be created by the recombination of
exons.
• Exon within a gene could be duplicated (Exon duplication).
• Introns greatly increase the probability that DNA duplications will give rise to
functional genes encoding functional proteins.
• The presence of introns increases the probability that a chance
recombination event can generate a functional hybrid gene by joining
together two initially separate exons coding for quite different protein
domains. exon shuffling.
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13. Horizontal Gene Transfer
• Horizontal gene transfer occurs when genetic information is passed
“sideways” to a relatively unrelated organism
• The extent of horizontal gene transfer is difficult to measure accurately and
has often been over-estimated.
• Transmission of genetic information from parent to offspring is termed
vertical gene transfer.
• The transfer of genetic material horizontally usually involves the use of
viruses, plasmids, or mobile elements such as transposons. Horizontal gene
transfer occurs not only for unrelated species, but for related species as well.
• virulence factors and antibiotic resistance are carried on bacterial plasmids.
• Transfer of a Ti-plasmid from bacteria to plant cells.
• Retroviruses are noteworthy for inserting themselves into the chromosomes
of animals, picking up genes, and moving them into another animal species
• type-C virogene shared by baboons and all other Old World monkeys. 5–10
million years ago a retrovirus carried the type-C virogene horizontally from
the ancestor of modern baboons to the ancestor of small North African cats.
Thus, the domestic pussycat carries the type-C virogene. However, other
cats that diverged more than 10 million years ago lack these sequences13

14. Horizontal Gene Transfer
• 5–6% of the genes in a bacterial genome are derived from
horizontal gene transfer.
• Instances of horizontal gene transfer are difficult to measure.
Therefore, horizontal gene transfer is often over-estimated.
Several reasons for this exist.
o Only a few eukaryotic genomes have been sequenced, but
hundreds of prokaryotic genomes have been sequenced. This
results in sampling bias.
o Homologs for genes may be lost in some lineages.
o Gene duplication then divergence gives rise to novel genes.
o Laboratory transfer of genes is easier than the real life
scenarios. And finally, during laboratory experiments, it is
difficult to completely purify away all of the eukaryotic DNA from
bacterial and viral genetic information. 14

15. Mutations
• New mutations provide a continuous source of variation.
Mutations with no effect on fitness are considered neutral.
Neutral mutations are not acted on by selection and are subject
instead to genetic drift. Selection operates against mutation
with a deleterious effect, and operates in favor of the extremely
rare mutations that have a positive effect on fitness. Selection
can operate simultaneously at hundreds or thousands of variant
loci within a population.
• Mutations rendering genes nonfunctional turn many duplicated
genes into pseudogenes that over time diverge into random
DNA sequences. However, rare advantageous mutations can
turn a second copy of a gene into a new functional unit able to
survive and spread through positive selection.
• Sequence comparisons make it possible to construct
phylogenetic trees illustrating the relatedness of species,
populations, individuals, or molecules. 15

16. Organismal complexity
• The evolution of organismal complexity generally correlates with
an increase in genome size, which occurs through repeated
duplications. Some duplications result from transpositions, while
others arise from unequal crossing-over.
• The mammalian genome contains genes, multigene families, gene
superfamilies, genome-wide repetitive elements; simple sequence
repeats; and repetitive elements in centromeres and telomeres.
• Complex genomes arose from four levels of duplication followed
by diversification and selection: exon duplication to create larger,
more complex genes; gene duplication to create multigene
families; multigene family duplication to create gene superfamilies;
and the duplication of entire genomes.
• Genetic exchange between related DNA elements by intergenic
gene conversion most often increases the variation among
members of a multigene family. Sometimes, however, it can
contribute to concerted evolution, which creates a family of nearly
identical genes. 16

17. HIV and Evolution
• The human immune system is capable of a response that
evolves on the molecular level through cloning of T and B cells
that match an antigen. HIV can undergo rapid evolution due to
the high mutation rate of its reverse transcriptase. Therapies
aim to slow the proliferation of HIV by targeting reverse
transcriptase and other viral enzymes.
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18. Conservative vs Non-conservative Seq
• Non-conservative: When amino acid changes
observed between two or more sequences do not
share the same side chain or R-group chemistry.
• Conservative: When amino acid changes observed
between two or more sequences do share the same
side chain or R-group chemistry.
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19. Homology
• Homologs are structures or objects that share a common
evolutionary origin.
• Objects with similar structure or function, but no common
ancestor are analogs.
• Homologs can be classified as orthologs or paralogs.
• Orthologs are homologous objects from different species that
arose from a common ancestor .
• Paralogs are homologous objects that are the result of gene
duplication within an evolutionary lineage (eg.species) and may
have different or similar functions.
• Identifying homologous sequences provides a basis for
phylogenetic analysis and sequence-pattern recognition
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20. Phylogenetic analysis
• Phylogenetic analysis attempts to describe the evolutionary
relatedness of a group of sequences.
• phylogenetic tree or cladogram groups species into a diagram
represents their relative evolutionary divergence. Branchings of
the tree that occur furthest from the root separate individual
species; branchings that occur close to the root group species
into kingdoms, phyla, classes, families, genera, and so on .
• The information in a molecular sequence alignment can be
used to compute a phylogenetic tree for a particular family of
gene sequences.The branchings in phylogenetic trees
represent evolutionary distance based on sequence similarity
scores or on information-theoretic modeling of the number of
mutational steps required to change one sequence into the
other. Phylogenetic analyses of protein sequence families talks
not about the evolution of the entire organism but about
evolutionary change in specific coding regions. 20

21. Genetic variation
• Genetic variation :genomic differences between different
species as well as between members of the same species.
• Members of the same species have genomes that are quite
different from each other.
• No two human beings have identical genomes unless identical
twins
• Mechanisms of genetic variation
• Rare mistakes in DNA replication and repair
• DNA recombination and the activity of viruses and mobile
genetic elements that can move into and out of the DNA
• Reassortment of the gene pool of the species into new
combinations during sexual reproduction.
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22. Polymorphism
• Molecular variation or Polymorphism: The number of polymorphic loci or the
fraction of polymorphic loci among several loci studied in a population or
polymorphism. It includes:
• Changes in nucleotides which could be transition or transversion. In the
transition mutation, a pyrimidine (C or T) is substituted by another
pyrimidine, or a purine (A or G) is substituted by another purine. The
transversion mutation involves the change from a pyrimidine to a purine, or
vice versa.
• Insertion or deletion of single nucleotides (indel)
• Variation in number of repeat of tandemly repeated sequences
(microsatellite, minisatellite, satellite).
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23. Mitochondrial DNA (mtDNA)
• Mammalian mitochondrial DNA is a small (15-20 kb) circular molecule,
comprising of about 37 genes coding for 22 tRNAs, two rRNAs and 13
mRNAs. Within the coding region cytochrome b is the most widely used
gene for phylogenetic work. This gene evolves slowly in terms of non-
synonymous substitutions.
• In the non-coding region the major control region for mtDNA expression is
the displacement loop (D loop), which has also been used in evolution
studies. The D-loop is also widely used in evolution studies and it has a rate
of nucleotide substitution five to ten times higher than that of nuclear DNA.
• mtDNA polymorphisms have been widely used to investigate the structure of
populations, interspecies variability, the evolutionary relationships between
populations or species and for the identification of maternal lineages.
• Mt DNA has some importance characteristics that include maternal
inheritance, high mutation rate, high copy number and lack of recombination
(unlike autosomal or X chromosome specific loci). The D-loop is mainly used
for intraspecies variation studies while the cytochrome b is for interspecies
variation. 23