Human inheritance - complexities.
Mutation.
Evolution.
Inheritance in human beings is, much more complex than pea plants.
We carry thousands of genes.
There are millions of possible combinations of these genes.
Each individual life is a unique combination of the many million possibilities.
We not only share similarities with our parents, and ancestors,
we are also unique combinations of them.
If we know the complete genetic makeup,
of both parents,
can we predict, the exact genetic makeup,
of their offspring?
The answer is an emphatic “no”.
There are many factors, which will determine the genetic makeup,
of the offspring.
We will summarise, some of the more important factors.
The cells in our body have 23 pairs, or 46 chromosomes.
We recall that gamete cells, the ovum and the sperm,
have only 23 chromosomes.
We inherit only one type of chromosome, from each parent.
For example, if we inherit chromosome 1 from the father,
we will inherit the other chromosome 1, from the mother.
If we inherit chromosome 2 from the mother,
we will inherit the other chromosome 2 from the father.
There is a 50% probability, that a particular chromosome,
is inherited from the father, or mother.
If a particular allele, is present in a parent,
there is only a 50% probability, that the offspring will inherit it.
We know that the father carries,
23 pairs of paternal chromosomes,
and 23 pairs of maternal chromosomes.
There is a equal probability, that an offspring, will inherit,
a paternal or maternal chromosome, from the parents.
The probability that we will inherit, all the maternal chromosomes,
from one parent, is one in several million.
If we take a deck of cards, and deal out four hands,
of 13 cards, what would be the probability, that we get a full exact sequence,
from Ace of hearts, to the King of hearts?
The probability is so low, that it practically does not happen, to us.
There is a equally low probability, that we will inherit,
all the paternal chromosomes from one parent.
Typically, we will inherit, a mix of paternal and maternal chromosomes,
from each parent.
Each child is a unique variant.
Nature seems to go out of its way, to create variants.
We are aware, that gamete cells, are produced by a process called meiosis.
In summary, during meiosis,
the cell replicates itself, to create 92 chromosomes.
It then divides itself twice.
Each gamete cell, has only 23 chromosomes.
Each gamete is a variant.
Each sperm cell, that the father produces, is a variant.
Each ovum cell, that the mother produces, is a variant.
When a sperm fertilises an ovum,
the resulting zygote, is a combination, of these two variants.
This is the reason, that even children of the same parents,
can be very different.
As if, this variation is not enough,
another subtle change, takes place during meiosis.
A process called, as crossover, or recombination takes place.
During this process, genes get exchanged,
between the maternal and paternal chromosomes.
This creates one more level of variation.
The end result, of all this variation, is the diversity, in humanity.
If we look around our family, our school, our town, our country,
or the world, we can see evidence, of this rich diversity.
Every human being is unique in some way.
We can say with confidence, that each and every human being,
has a unique DNA gene print.
Maybe sometime in the future, it can be used, as a unique I.D.
Mutations are due to transcription error.
There are trillions of cells, in the human body.
These cells have a limited lifespan.
They need to be constantly replaced.
Somatic cells, replicate themselves, to create identical copies.
It is the DNA, which is the first and the foremost, in the replication process,
of mitosis.
Amazingly, DNA makes perfectly identical copies, trillions of times.
But, sometimes, rarely, very very rarely, it makes a mistake.
It does not make an exact copy.
It is estimated that there could be one error,
for about 10 billion base pairs, that are replicated.
When this happens, we call it as a transcription error.
There is a probability,
a transcription error can happen, while making the copy.
This is called as mutation.
In some cases, some factors in the environment, could be responsible for mutation.
These factors are called mutagens.
Some examples of mutagens are:
Certain chemicals, X-rays, atomic radiation, etc.
When the first atom bombs, were exploded over Hiroshima, and Nagasaki,
there were some survivors.
They were exposed to atomic radiation.
Many future generations of most of these survivors, had genetic birth defects.
This was due to exposure to atomic radiation, of the survivors.
Certain chemicals like pesticides, pollutants, and habits like smoking,
can also be triggers for mutation.
We need to be careful, to protect ourselves from environmental factors,
which can potentially result in harmful mutations.
We are aware, that genes are a sequence of the bases, A, T, C, G.
These bases are organised as three letter codons.
Each codon, specifies one of the twenty amino acids.
A protein is a chain of amino acids.
Each amino acid corresponds to a three letter codon.
The sequence of the codon is very important, in determining the right protein,
to be synthesised.
Each protein has a very specific function, to perform in the human body.
The gene performs the function of giving the template, to synthesise the protein.
If the gene has a spelling mistake, what will happen?
There are many possible things, that can happen.
We will discuss some of the possible outcomes of mutation.
There are vast areas, in the human genome, which are believed to be unused.
If a mutation happens, in these areas, it would make absolutely no difference.
The cell does not use these portions of the DNA, to synthesise proteins,
or any other regulatory function.
Even if a mutation happens, in these areas, of the DNA,
the cell will continue to function normally.
This means that if a spelling mistake, happens in the area,
of the unused DNA, it will not make any difference.
There are 20 amino acids, that the human body uses.
Each amino acid, corresponds to a three letter codon.
With three letters, we can get 64 unique combinations.
But, our body uses only 20 amino acids.
In some cases, multiple codons represent the same amino acid.
For example, the codons
G, U, U.
G, U, A.
G, U, G.
G, U, C.
are all genetic codes for the same amino acids, called valine.
If a mutation results in G, U, G, being misspelt as G, U, C,
there won’t be any problem,
since they both mean, the same amino acid valine.
The protein that will be synthesised, will be exactly the same.
So, this kind of mutations also don’t matter.
In some cases the mutation, will result in a code,
for a different amino acid.
Proteins are a long chain of amino acids.
Only certain amino acids, in this chain, participate in bio chemical reactions.
If the mutation, happens to be in a inactive amino acid, of a protein,
it will not make any difference.
The protein will continue to function, as if nothing happened.
So, this kind of mutations also don’t matter.
These kind of mutations, which have no impact,
are called neutral mutations.
Fortunately, a majority of mutations, that do occur are neutral mutations.
There are a few types of mutations, which are harmful.
We will discuss a few of such cases.
If a mutation happens, to a TATA box,
it could stop a gene from getting transcribed.
This might result in non production of a required protein.
A substitution can happen, when the cell produces, a wrong amino acid,
which produces a wrong protein.
This protein could be harmless.
In some cases, the wrong protein, could be harmful.
This could result in death of the cell.
Typically, death of one cell, does not cause any harm, to a human being.
This is because, millions of other cells are doing the same function.
For example, if one red blood cell, produces a nonsense protein,
instead of a haemoglobin protein, other red blood cells,
will continue to perform the function.
The function of the body is not impacted, by this type of mutations.
Insertions and deletions, in the genetic code,
causes different kind of problems.
Since the genetic code, is a sequence, instead of one error,
we land up with a series of errors.
This could mean production of a large number of wrong amino acids.
The resulting protein, could be potentially harmful.
We will discuss a case, where one character, is accidentally inserted.
For example, the sequence,
A, U, G.
C, C, C.
G, G, C.
U, A, U.
C, C, G.
would result in producing the amino acids:
Methionine.
Proline.
Glycine.
Tyrosine.
Proline.
If a character ‘C’ gets accidentally inserted, between the second and the third codon,
the sequence will change to,
A, U, G.
C, C, C.
C, G, G.
C, U, A.
U, C, C.
G.
This will result in a different sequence of amino acids, identified as,
Methionine.
Proline.
Arginine.
Leucine.
Serine.
This has resulted in three wrong amino acids.
In a real case, it would be thousands of wrong amino acids.
The resulting protein could not only be a nonsense protein,
it could potentially be a harmful protein.
Deletion of a character can result in a similar error,
of a wrong sequence of codons.
Insertion and deletion, have the potentially additional threat,
of changing the sequence of the entire downstream codons.
Both these cases, can result in production of a potentially harmful protein.
The cell has a mechanism for identifying some transcription errors.
When the cell is successful, in identifying a transcription error,
the cell can self destruct.
This process is called “apoptosis”.
This quality control mechanism comes in useful, in checking many,
potentially harmful mutations.
An organ has many cells.
Death of a single cell, is not of significant consequence.
The organ will continue to function normally.
So far we have discussed, mutations in somatic cells.
All the cells, with the exception of reproducing gamete cells,
are somatic.
Mutations in somatic cells happen, after life is conceived.
Most of it would happen, during the adult phase of our life.
As we have discussed most of them, would be harmless.
Some of them, could be potentially harmful, even dangerous.
We need to take care, of these cases.
Gametes are the reproductive cells.
Sperm and ovum are reproductive cells.
Even without mutation, reproductive cells, can pass on,
defective alleles to the next generation.
We have discussed, dominant and recessive traits.
We are aware, that defects and diseases, can be inherited.
This type of inheritance, has nothing to do with mutation.
Mutations in gametes, are a special case of mutation.
During meiosis a gamete cell, could undergo mutation.
We are aware that there are thousands and millions,
of gamete cells.
Only one sperm cell, which meets with a ovum, gets fertilised,
resulting in a zygote.
In the case of males, only one in several millions of sperm cells,
result in fertilisation.
If a mutation has happened, in a sperm cell, for example,
in most cases, it will not make a difference,
because it will not fertilise an ovum egg cell.
In a rare case, it might fertilise, an ovum cell.
The mutation will be passed on, to the next generation.
In case the mutation was a harmful mutation,
the offspring will inherit this harmful mutation.
We must reiterate, that a vast majority of child births, are healthy.
Only one to three percent, of child births, have inherited birth defects.
A lot of emphasis in medical research, goes to these abnormal cases.
This is understandable.
Only these small percentage, require special attention, and medical care.
We can hope that genetic science, will help prevent, reduce, or alleviate,
these kinds of birth defects.
One case of mutation requires special mention.
This is a mutation which results in a cancerous cell.
In a adult body, the rate at which new cells, in a tissue are formed,
and old cells die, are in balance.
This produces a steady state, when the tissue does not increase in size.
If the mechanism regulating the cell divisions are altered,
affected cells,may produce new cells, faster then old cells are removed.
This results in a growing mass of tissue, known as a “tumour”.
A tumour that is not harmful, is a benign tumour.
If however, the tumour cells grow into the surrounding tissues,
disrupting their functions, it is said to be a malignant tumour.
Malignant tumours are composed of cancer cells,
which have lost the ability to respond to the normal control mechanisms,
that regulate the cell growth.
They are capable of unlimited multiplication.
They can also spread to other parts of the body.
This can be life threatening.
Unfortunately, the incidents of cancer, is increasing.
A vast amount of research is going into,
prevention and treatment of cancerous disease.
In all this discussion about mutation, it would be easy, to forget about,
one more type of mutation.
It is possible, that some mutations are beneficial.
Beneficial mutation, is at the root of evolution of life.
We are all mutants.
All the forms of life, that we know of are mutants.
We all evolved from primordial single celled organisms.
But for mutation, we would all be some kind of bacteria.
How is it, we don’t seem to be much different, from our grandparents?
To perceive evolution, we need to think over long periods of time.
We feel confident, that we are quite different from chimpanzees.
Over millions and millions of generations,
and millions and millions of mutations,
we did evolve from apes to human beings.
Even today, we share about 95% of our genes, with chimpanzees.
If we trace our ancestors for about 2.5 million years,
we can find chimpanzees.
If we go back many millions of years, we can trace our fish ancestors.
If we go back billions of years, we can trace our bacterial ancestors.
Mutations become obvious, over many generations, spread over a long period of time.
We are conscious that we are much more evolved,
than the first homo sapiens, that inhabited Earth, about 200 thousand years ago.
We can easily believe, that we are superior, to cave men,
who lived 10000 years ago.
We can also appreciate, that we did not achieve, this transition, in one giant leap.
Mutant by mutant, we evolved from all these forms of life.
When Charles Darwin proposed theory of evolution, he did not know the existence of ,
DNA and genes.
He discovered it by observing different species, and variants of the same species.
He also studied fossils of extinct species.
When he was in galapagos island, he studied a species of birds,
called Finches.
The same birds had different types of beaks, in different islands.
This means that the same species, evolved different kind of beaks.
Why would they do that, he wondered.
Some finches had beaks, which could crack hard nuts.
Some finches had long beaks, which could extract nectar from flowers.
Later he realised that the finches had evolved different kind of beaks,
to adapt to the kind of food available in its native island.
This simple and powerful conception of adaptation,
is the very basis of the theory of evolution.
After DNA and genes, were discovered, we can now understand,
how the genes of the finches, mutated and found a successful variant.
All forms of life evolved to better adapt to the environment.
They also evolved to discover new life styles.
Land based animals, evolved from fish.
Birds evolved from dinosaurs.
Every generation of life, is a new mutant.
The DNA is slightly different, in the new generation.
Over many generations, the differences become significant.
When the mutations were better adapted, or found better opportunities,
the new variant of the genes, reproduced successfully.
The mutants which could not adapt, died out.
Over thousands, millions, and billions of years,
nature created a rich variety of life forms.
This is what we see around us today.
Life is still evolving.
Thousands of years ago, adult humans could not digest lactose.
Lactose is present in milk.
After humans, domesticated animals like cows and goats,
they learn to use the milk for food.
The human genes evolved, to synthesise an enzyme, called lactase.
With lactase, they were able to digest milk, and use it as a food.
This is a small example, of genes evolving to adapt.
If we expand our thinking, along these lines , we will understand all of evolution.
Using gene analysis, it is possible to trace our distant ancestors.
Scientists have traced, the evolution of human beings, using gene analysis,
to the very first homo sapiens, who first appeared in Africa.
It is believed that human beings, migrated out of Africa,
about 50000 years ago.
They went on to populate, different parts of the world, we know today.
Using gene analysis, scientists are able to trace, their migration paths.
When they settled, in different parts of the world,
they were able to adapt, to the local environment.
The relationship, between different forms of life,
can also be studied using genetic analysis.
Closely related species, will have more genetic similarities.
It is also possible, to determine, which species descended, from which species.
This is how scientists, were able to discover that mammals, evolved from fish,
and birds evolved from dinosaurs.
They are also able to trace, that all forms of life,
evolved from some kind of unicellular organisms, called prokaryotes.
If we really think about it, we realise, that evolution of all forms of life,
is fundamentally the evolution of genes.
Forms of life, is just the expression of genes.
Nature invested millions and billions of years,
evolving different designs, of genes.
Over the long term human beings, and other forms of life,
will continue to evolve.
We will leave it to you, to imagine, what we will evolve into.