The document discusses neutral theory of molecular evolution, which holds that most genetic changes are due to neutral mutations that do not affect organismal fitness. It proposes that neutral mutations accumulate over time at a constant rate, allowing relative divergence times to be estimated. The theory aims to explain high genetic variation and presence of neutral substitutions between species. Several lines of evidence are presented, including comparative rates of evolution between functionally important and unimportant genes and gene regions.
2. Neutral theory of evolution holds that most
evolutionary changes at the molecular level,
and most of the variation within and between
species, are due to random genetic drift of
mutant alleles that are selectively neutral.
The theory applies only for evolution at the
molecular level, and is compatible with
phenotypic evolution being shaped by natural
selection as postulated by Charles Darwin.
3. NEUTRAL MUTATION
• A neutral mutation are changes in DNA
sequences that are neither beneficial nor
detrimental to the ability of an organism to
survive and reproduce.
• The neutral theory assumes that most mutations
that are not deleterious are neutral rather than
beneficial.
• In population genetics, mutation in which natural
selection does not affect the spread of the
mutation in a species are termed as neutral
mutations.
4. • In 1968, Motoo kimura propsed:-
• According to this, most genetic variation , observed in
natural populations, is due to the accumulation of
neutral mutation that do not affect the phenotype of
the organism and are not acted on by natural selection.
• EXAMPLE:- A mutation within a structural gene that
codes for glycine codon from GGG to GGC does not
affect the amino acid sequence of encoded protein.
• These mutations does not affect phenotype, they
spread throughout the population according to their
frequency of appearance and random genetic drift.
5. Two observations underlie theory:-
1.) Most natural populations harbor high levels of
genetic variation higher than would be expected if
natural selection were the evolutionary force
primarily responsible for influencing level of genetic
variations in populations.
2.) Many mutations in sequences of genes do not alter
the proteins encoded by those genes-
Virtually always true for synonymous substitutions.
Sometimes true for non-synonymous substitutions.
6. Kimura and his collegue Tomako ohk outlined five principles
that governs the evolution of genes at the molecular level.
(1.) For each protein the rate of evolution in terms of
amino acid substitution is approximately constant
with regard to neutral substitution that donot affect
protein structure and function.
EVIDENCE:-
The amount of genetic variation between the coding
sequence of the human alpha-globin and beta-globin
genes is approximately same as the difference
between the alpha and beta globin gene in the
horse.
7. (2.) Proteins that are functionally less important for the
survival of an organism or part of a protein that are
less important for its function tend to evolve faster/
accumulate amino substitutions more rapidly than
the more important ones.
EVIDENCE:-
Histone proteins are critical for survival which help in
nucleosome formation in eukaryotes. Histone genes
tolerate very few mutations and have evolved
extremely slowly.
Fibrinopeptides which bind fibrinogen to form a clot
evolve very rapidly.
8. (3.) Amino acid substitutions that donot significantly
alter the existing structure and function of a protein
are found more commonly than the disruptive amino
acid changes.
EVIDENCE:-
When comparing the nucleotide/ coding sequence
within homologous genes of modern species
nucleotide sequences are more likely to be occurred
in the wobble base as mutation in this are silent.
-Conservative substitutions(substitution with a similar
amino acid, such as a nonpolar one) are fairly
common.
9. - Non conservative substitutions, nonsense and
frameshift mutations are very rare within
coding sequence of genes.
- Also, introns sequences evolve more rapidly
than the exon sequences.
10. (4.) Gene duplication often proceeds the emergence of
a gene having a new function.
EVIDENCE:-
When a single copy of gene exist in a species, it
usually plays a functional role similar to that of the
homologous gene in another species. Gene
duplication have produced gene families in which
each family member can evolve somewhat different
functional rate.
Example:- globin and hox gene family.
11. (5.) Selective elimination of definitely deleterious
mutations and the random fixation of selectively
neutral or very slightly neutral or very slightly
deleterious alleles occur for more frequently in
evolution than selection of advantageous mutants.
EVIDENCE:-
Non conservative mutations usually have a negative
effect on phenotype of organisms so are effectively
eliminated from population of natural selection.
Example:-
A nonconservative mutation in the beta-globin gene
produced the Hbs allele which gives an individual
resistance to malaria in the heterozygous conditions.
12. EVIDENCE SUPPORTING NEUTRAL THEORY-
• Psuedogenes (dead genes that have no
function and no fitness effect) evolve very
fast.
• Synonymous codon positions (3-fold, 4-fold
degenerate sites) evolve faster than a non-
synonymous sites, and should evolve with a
constant rate (not always true).
• Genes that have very important functions
should evolve faster.
14. • Concept was given by Zuckerkandle and
Pauling(1965).
• It is used to predict the phylogeny of organism
and it can also enable us to estimate the
absolute time since taxa diverged.