Mystery of the Y Chromosome Resolved – How it Prevents Male Extinction

Females are 100% Female. Males are 50% Male

Chromosomes and Gender Basics

We know that our body cells contain chromosomes which carry our genetic material DNA which codes to form genes and which are in turn responsible for the entire development and functioning of our body. So in software terms it is like –

• DNA is the programming language which has only 4 keywords A,T,G and C
• Genes are small programs (or more correctly Classes) written using this programming language
• Chromosomes are like the software libraries which contain all these programs (Genes).

We also know that Humans have 23 pairs of Chromosomes – ie 46 in all. Of which one pair (called the sex chromosomes) determines the sex of the person. This pair can be either a XX or a XY combination. If it is XX then the person is a female, if it is XY then the person is a male. X chromosome carries the feminism or the female body features while Y chromosome carries the male body features. Please note that there is no YY combination ie no person can have two Y-Chromosomes. And so very rightly, all males are 50% Females!

As we can see, Females carry only X chromosomes, while males carry both X and Y chromosomes. So it is actually the male (Father) whose chromosome decides whether the offspring will be a male or a female. These are the basics. Now over to the mystery of the Y Chromosome. But before that..

The DNA in each human cell gets damaged on an average 20,000 times every day!

And this damage definitely needs to be repaired continuously failing to which the body will ultimately fail!

DNA Damage and Genetic Repairs – How Chromosomes Self Heal their wounds via Recombination

We know that each chromosome comes with a double helix strand (See Below).

DNA Double Helix Strand

And each such Chromosome comes in a pair ie two similar Chromosomes – one received from the father and the other one received from the mother.

The DNA in these chromosomes can get damaged due to

• Exposure to Ultra Violet rays from Sun
• Exposure to X rays
• Chemicals in the environment
• Toxic content in the food,  etc.

Hence it is very important for chromosomes to have a mechanism to repair the damaged DNA, because the normal healthy functioning of the entire body finally depends on how healthy (meaning accurate) the DNA gene sequences in its chromosomes are.

DNA Damages if left unattended might creep into the offsprings (children) of the affected individual, and if the damage is related to a portion of the DNA which plays a crucial role in the functioning or development of the body, then there are real good chances that the offspring might not survive or might lead a miserable life due to its damaged genes resulting in malfunctioning organs.

Or say, if the damage was not a major one, and the offspring somehow survived, and then the offspring itself got some additional DNA injuries and damage during its life time, and it passed on both (its acquired defect as well as inherited genetic injuries) to its offspring, and so on. Now this causes a gradual accumulation of defective genes and this irreversible genetic decay might finally result in the extinction of the entire species in the future.

So if there is no repair mechanism in place to correct the damaged DNA and fix the typos in DNA code caused because of the damage, the survival chances of that species are very little.

The capacity to blunder slightly is the real marvel of DNA.  Without this special attribute, we would still be anaerobic bacteria and there would be no music.  – Lewis Thomas

To counter the possibility of defective genes, evolution has developed multiple self healing mechanisms in its genetic material. And in this article we will be talking about the healing mechanism related to the fixing of DNA damages where both the strands of DNA are damaged or broken (called DSB or Double Strand Breaks) and the healing mechanism that takes place before Meiosis. Meiosis is the process of creating haploid cells (like sperms and eggs) that would go on to become offsprings.

DNA Programming Rules

Note that every Chromosome has a double helix DNA. And each strand in the double helix is an identical copy of the other in terms of Nucleotide Pairs. What does it mean? We know that DNA is coded using four molecules A (Adenosine), T (Thymine), G (Guanine) and C (Cytosine) and the rule is that A can only pair with T, and G can only pair with C.

So if one strand in a double helix reads AGCTGTC, then the corresponding location in the other strand of the double helix will always read TCGACAG

Single Strand Breaks

Whenever there is damage to a portion of the DNA in one strand (Single Strand Breaks), the cell fixes it by copying the correct code from the other unbroken strand. Say if the code in the unbroken strand is T, then it is obvious that the missing code in the broken strand is A because only A can pair with T. Similarly if the opposite strand has G, then the missing code is definitely C because only C can pair with G. (See Video Below) Simple, isn’t it?

Please note that the above video has a small mistake in that, the nuclear DNA double helix is right handed, while the above video shows a left handed double helix.

Double Strand Breaks

Double Strand Breaks or DSBs are DNA damages where both the strands of the DNA are broken at a given location. How to fix this DNA damage? It cannot be fixed using the method shown in the above video. Because we don’t have any reference within the Chromosome now as information is missing in both the strands of the Double Helix.

The answer lies in that each chromosome comes with a functionally identical pair (Remember there are 23 pairs of chromosomes). So if the cell identifies a damaged Chromosome with a Double Strand Break, it simply copies that portion of the DNA from the other chromosome in the pair into the damaged one. So each Chromosome in a pair acts as a backup copy for the other chromosome in the pair.

This process of correcting the mistakes in the genetic code happens during the formation of gametes (ie sperms in males and eggs in females) because it is finally from these gametes that the offspring (child) will be created. For those who remember the biology text books, this genetic proof reading and editing occurs before this cycle called Meiosis. Meiosis is nothing but the creation of gametes (the cells required for reproduction).

DNA was the first three-dimensional Xerox machine.  – Kenneth Boulding,

Infact the very reason sexual reproduction evolved was probably because of the need for this repair, is what many biologists think. Sexual reproduction gives two pairs of functionally identical chromosomes, and assuming that both pairs of the same chromosome of the same cell selected for meiosis do not get damaged at the same time (which is a fair assumption), one chromosome in the pair (which came from one parent) can be used to repair any damages in the other chromosome in the pair (which came from the other parent).

Note that when a copy occurs of a portion of DNA from the undamaged chromosome to the damaged chromosome, it does not mean that the actual Genetic Code (the ATGC sequence) of undamaged one is EXACTLY the same as that of the damaged chromosome. Instead they can be considered to be functionally identical. That is because each chromosome from a pair comes from a different parent.

So if there is a gene in one parent that codes to create blue eyes, then the other parent will also have the same gene at that location. However the gene of this other parent might code to create green eyes – and so obviously the genetic code will be slightly different in both the chromosomes. However their function remains the same ie to code for the eye color.

Now if both the chromosomes containing these genes were not damaged in a cell which is about to undergo Meiosis, then the resulting gamete cells will contain either a chromosome coding for blue eyes or a chromosome coding for black eyes.

But say during Meiosis if it was found that the chromosome containing genetic code for blue eyes was damaged, then the black eye code from the other chromosome (which lies in the same location in the other chromosome) will be copied over to replace the blue eye code in the damaged chromosome. So the resulting gamete cell will always have the chromosomes coding for black eyes.

Note that gamete cells are haploid in nature ie they do not come in pairs and hence have only 23 Chromosomes, so the 23 Chromosomes from both the parents is used to form the final pair ie 46 Chromosomes during Conception.

Perfect isn’t it? So Good so far. Now over to the mystery of the Y Chromosome.

Mystery of the Y Chromosome

Assuming that you have understood the above repair mechanism of chromosomes, you should have got a hint about the mystery by now. We know that females have XX chromosomes which is fair enough, and any damage in one X chromosome can be corrected by simply copying the genetic data from the other X chromosome, as mentioned in the above process.

But what about males? they have XY Chromosomes! So what will happen if the Y chromosome which decides everything about the man being a male gets damaged? There is no backup for it in the form of other chromosome in the pair, because the other one is a X Chromosome! We cant copy X chromosome contents (female specifications) into Y Chromosome (male specifications), that would have the potential to make all males a female!

But why haven’t males become extinct yet? :)

Or say, in an XY combination, if there is a damaged X found during meiosis and if the contents of Y are simply copied over to X, then all females would become males because such X chromosomes would have Y content in those genetic portions which decides gender. So definitely there is no way that the normal proof reading, copying and editing mechanism applied to other pairs of chromosomes can be applied to a XY pair. It has to be something totally different, if at all it exists. And it does exist because otherwise males would have gone extinct long back because of accumulated genetic defects over time and the inability to fix them. So then What is this mechanism that has been protecting and repairing the Y Chromosome throughout its evolution?

This was the fundamental mystery of Y Chromosome which bothered geneticists for long. Y Chromosome is relatively very small in size compared to the X Chromosome, its just about one third the size of its female counterpart.

Most of the genetic material in Y Chromosome was thought to be junk. This was because as Y Chromosome had no corresponding chromosomal pair, it was thought that most of Y Chromosome had inactive defect filled genes accumulated overtime. Very few genes, were thought to be active in Y Chromosome – the most important one being SRY.

SRY – The Sex Determining Region of the Y Chromosome

It is generally believed that males are males because they have Y Chromosome in their cells. But note that males also have X chromosomes in their cells, so what prevents males from becoming females?

Just because a person has XY chromosome does not make him a male. When a human embryo is born, for the first 40 days after conception – both males and female embryos will look and develop alike in the womb. Before 40 days it is NOT possible to just look at the embryo and tell whether the child is going to be a boy or a girl, because both male and female embryos look alike then.

After 40 days of conception, it is the SRY gene in the Y Chromosome which triggers the masculinization of the embryo. This SRY gene is what causes the embryo to develop male sexual organs and into a proper male. If this gene is NOT triggered at the right time, then X chromosome in the pair will take over and trigger the development of female sexual organs in the embryo, and this will happen in spite of the child having XY Chromosomes! So it is just the triggering of a single gene in the Y Chromosome that has prevented all males from becoming females so far in history :)

Mystery Solved – The Self Healing Mechanism of Y Chromosome via Genetic Palindromes

Around 5% of Y Chromosome shares its genes with X Chromosome and hence this portion can be repaired using X Chromosome. But 95% of the Y Chromosome, and this is the part of the Y Chromosome which makes a person male, cannot be recombined with the X Chromosome because ONLY Y Chromosome contains these genes and they are exclusively there to make the person a male and hence not found in the female counterpart – X Chromosome.

So how does the Y Chromosome repair any defects or errors or damages in this most important 95% of it? This was a major puzzle faced by Biologists for a long time.

Finally it was discovered in 2003, that nature has a great elegant solution to repair the Y Chromosome which comes without a pair. The answer lied in the beautiful arrangement of the genetic sequence of the Y Chromosome. Y Chromosome has 78 genes, and most of it (ie the most important 95%) was grouped into 8 duplicate palindromes in the genetic code of Y Chromosome.

A Palindrome is a sequence of letters which reads the same in either directions – like the name of the language Malayalam. You reverse the sequence of characters and it still reads the same.

So what this actually means is that Y Chromosome has a second set of these 8 palindromic sequences copied on to itself in the reverse order, and so each can now act as a backup for the other set.

Whenever the cell finds that any portion of the Y Chromosome is damaged (ie it not being a palindrome), the cell then replaces it with its palindromic copy from the other set by folding over to itself. Simple and beautiful, isn’t it?

Say the Y Chromosome contains the following set of Palindrome codes,

ATGCGCGT is in one arm of the chromosome and its palindromic reversal  TGCGCGTA is in the corresponding location on the other arm of the Chromosome.

Now say strand is broken at X show below in one arm.

ATXXGCGT

The Y Chromosome simply imposes the gene sequence on the other arm at the corresponding location by bending over to itself. Since the other arm has the same palindrome in reverse order, when the Y Chromosome bends over to itself both the palindromes overlap in the same direction, and the missing sequence can be easily copied over from the intact version of the palindrome to the broken one!

The Y Chromosome is only passed from males to males ie from Father to Son and women never have this Y Chromosome.

Females also have a similar set of DNA that gets passed on only from mothers to children. This is the mitochondrial DNA which comes directly from the female egg, and hence in both boys and girls, their mitochondrial DNA always comes from their mother.

So Y Chromosomes can be used to study male ancestry in a population and determine the male geneology, while mitochondrial DNA can be used to study female ancestry and hence to determine female geneology in a population. (See The Science & Genetics behind the Vedic Hindu Gotra System)

And finally,

We are machines built by DNA whose purpose is to make more copies of the same DNA. This is exactly what we are for. We are machines for propagating DNA, and the propagation of DNA is a self-sustaining process. It is every living object’s sole reason for living. – Richard Dawkins

Part 2 (Coming Soon) – Mystery of the Y Chromosome – Will Y Chromosomes become extinct and hence cause male extinction?

References:

• DNA Repair
• DNA Damage and DNA Repair
• Understanding Genetics
• Y: Waving, Not drowning
• Wikipedia – Meiosis
• Wikipedia – Y Chromosome

Download HitXP Mobile App