ARTICLE #057

The X-Chromosome Match

2021-08-05 Ellie

(https://dna-explained.com/2014/01/23/that-unruly-x-chromosome-that-is/)

How the X chromosome recombines and is passed from generation

to generation

IMG source from Wikipedia “200px-Drosophila_XY_sex-determination”

The X chromosome is a chromosome that occurs in humans and other mammals. The X
chromosome, which contains the majority of the gene expression for males and females, recombines
during meiosis to produce sperm and eggs. In humans, it consists of approximately 47% non-
repetitive DNA sequence from both parents. The X chromosome spans more than 155 million base
pairs and represents about 7% of the total DNA in human cells.

The X chromosome is so named because it is the first human chromosome to be discovered, with a
German team led by FC Schleiden and TM Schwann first discovering it in 1831 - Cytogenetics has
come a long way since then!

From this point on I will only refer to the X chromosome as "X”. All the information I give will be about
female genetics. Male genetics will be not discussed this time because it is not as complex as female,
and it would just be overkill to have info about both genders.

The X chromosome is a large, and complex, piece of DNA. It contains 3000 protein-encoding genes
(more than any other human chromosome), and more than 6000 total genes (almost twice that of the
second most gene dense chromosome- Y).  It makes up almost 6% of our genome.

The X chromosome is known for having the most genetic variation between different people.
The Y chromosome is also significant in this regard, but the X has more variation simply
because it is longer.

The X chromosome has more genes than any other human chromosome. It is the largest piece of
DNA in a single chromosome and contains thousands of protein-encoding genes. Its size spans ~155
Million base pairs, which indicates that it likely evolved relatively recently in our genomes. The genes
located on the X are mostly involved in directing protein synthesis; however, they also encode some
proteins involved in structural maintenance and transcriptional regulation.

The X chromosome is the only human chromosome with no LINE (long interspersed nuclear element)
retrotransposable elements, which suggests that it has been relatively protected from mobile genetic
elements and that it has existed for a much longer time. This is all very interesting, but what does it
mean?

Basically, the X chromosome is important because it is a large and complex chromosome that
has an extreme amount of variation between the two copies in a cell, and it also encodes the
majority of gene expression for males and females. This means that all (or at least most) of the
genes involved in sex determination are found here, including SRY (sex-determining region Y).  These
factors make X extremely important for various biological processes.

X chromosome's role in sex determination

I will now start talking about the X chromosome's role in sex determination and a bit about how it
works. I will give a general overview of genes on the chromosome, and then talk more specifically
about SRY (sex-determining region Y).

This is the first thing that I am going to talk about, so I will try to keep it short so that you don't lose
interest. Many female mammals have another X chromosome in addition to their own. However, only
in humans does this X have a special function and be crucial for sex determination.  This is because it
has a Y-like gene called SRY on it.

There are many different forms of the SRY gene; however, they all are related to the regulation
of sexual development.  For example, the SRY gene can activate the transcription of various genes
and induce differentiation into testicular or ovarian cells depending on which developmental pathway
(gonadal differentiation) is activated.
The SRY gene can also affect the formation of testes in the embryo. This occurs because SRY is
crucial for inducing SOX9, which induces Leydig cells or Sertoli cells. Leydig cells produce hormones
such as testosterone, and Sertoli cells help mature sperm, but both play a role in sex determination
and sexual development.  Because of this role in sexual development, the SRY gene is critical for
fetal development in humans with XY karyotypes. This is why women with complete androgen
insensitivity syndrome (CAIS) have XY karyotypes and are phenotypically female.

IMG source from Wikipedia “PBP Protein SRY”

SRY is not the only gene located on the X chromosome; however, it is by far the most important in
terms of sex determination. It encodes a protein that plays a crucial role in directing sexual
development. Without this gene, human embryos will develop into females. A little more detail about
SRY.

In humans, the SRY gene is expressed in all cells; however, it is only essential for sex
determination in developing embryos. This means that once the embryo has developed into a fetus
and later a human, SRY is not important at all.  It only has an active role when determining the sex of
the embryo.  This phenomenon is also seen in mice and other mammals.

SRY is located on both the X and Y chromosome; however, only organisms with a Y chromosome will
develop into males. The SRY protein is short (200 amino acids), has a unique N-terminus, and has
various transcription factor domain motifs. It belongs to the SOX gene family, which encodes
transcription factors that are involved in directing embryonic development.  Therefore, SRY plays a
crucial role in directing sex determination. Without it, XY embryos become females. The SRY gene is
also the first male-specific gene to be expressed in the fetal gonad. If the SRY is not expressed, then
the gonad will develop into an ovary instead of testes (in XX embryos).

Recombination and Yeast Y

The X chromosome can, when it is able, or at least has the capability to recombine. This means that
the X and the Y chromosomes do not just sit there at more or less constant proximity, they can
separate and come together again to form a stable kind of shared genetic material. The yeast Y
chromosome is a compact little affair of just six components (in humans, the Y chromosome has
about 400) - it is of course much bigger in humans than in yeast.

The yeast Y has some interesting features that are tantalizingly relevant to the human situation.

For example, the Y chromosome bears coding sequences for multiple proteins, but as far as we know
these proteins never get expressed in the cells.

We do not know if they are ever "expressed" in any way unless there is a mutation that results in
expression.

But this separation of "genetic material" into parts with multiple functions on the yeast Y chromosome,
and genes with no function on the human Y, could tell us something about how evolution works
between humans and primates - what we might call an evolutionary "paradox". We have been told
that the Y-chromosome is very stable. The chromosome is said to be "virtually identical" in many (if
not all) mammals, implying no recombination has taken place after the divergence of mammals from
their common ancestor. Yet the Y-chromosome is known to be made up of recombination hotspots.

So the question arises: what is going on? Is recombination taking place at all?

The conclusion that can be derived from the yeast Y is that recombination may not be as rare as we
might think. It might happen more, on average, in mammals than in yeast. The only evidence for this
(so far) comes from a study of genetic material from 1000's mammalian sperm cells. The study found
that about 1/3 of those sperm cell's Y-chromosomes had recombined.

However, the Y chromosome sequences in mammals are unique: they do not contain any of the "junk
DNA" that is so common on the rest of the chromosomes. The expression of SRY is a very powerful
event in fetal development. But, so far as we know, the human Y chromosome has no other
function except to make an embryo male.

Recombination – The Next Problem

First, there were multiple reports of women having more matches than men. It is to be anticipated to
some degree because women have so much more forebears in the mixture, especially when
compared to other wives. But the amount of differences between what women think they have and
what men think they have is also striking. Women’s telomeres are shorter on average than men’s,
although this does not appear to be true in all women (for example, the shortest telomeres in the
world also belong to a Chinese woman).

This results in an obvious problem: How can maternal DNA affect offspring if it doesn’t get
passed down? It can’t. Add to this that the DNA of a woman’s mother or grandmother should not
affect her children, yet it does.

This is because there are two types of recombination, or crossovers, which occur during egg
and sperm production. Standard crossovers occur between each chromosome (we carry 22 pairs)
and ensure that we have an even number (23) of chromosomes after we are conceived. Without
recombination, we would have an uneven number of chromosomes and either be male (XY) or female
(XX). The second kind of recombination occurs only between homologous chromosomes, such as
crossing over between the chromosome carrying your grandfather’s DNA and your mother’s
chromosome holding your grandmother’s DNA.

Recombination is important because it gives rise to a new combination of alleles that might
not have occurred had recombination not taken place. Some of the most striking evidence for
these crossovers comes from the work that was published in 1999, done by a team at Duke
University. The team analyzed whole genomes from two couples with the same husband and wife.
They started by making a 90% identical "parental sequence" – basically their own DNA sequences.
This was then compared with another 90% identical parental sequence that they obtained from an
unrelated couple. The results showed that these two "parental sequences" had not been passed down
unchanged, but had recombined 20 times in both couples.

Current research has shown that it is not genetic material that is recombined – it is the gene
sequences themselves, which are moved around without changes. In egg and sperm formation there
are large numbers of crossovers taking place in many cells within a woman’s pelvis. For this reason,
we say that the differences between human sperm cells, for example, are likely to be greater than the
differences between hair cells (from your head) and brain cells.

The implications of this are becoming clear: How some of our genetic material is selected and
passed on appears likely to have a massive effect on how we can identify and eliminate
genetic diseases. But more importantly, it opens up a whole new field of study into how genes are
expressed during embryonic development.

Here’s what I can tell you.

 The X chromosome matching will show you that you do have a shared ancestor in history.

 The amount of DNA shared is not a reliable predictor of how long ago you shared that
ancestor

 Different DNA matches can be close or far away from your own. Even if you share a lot of
DNA with someone, that may not mean either of you are related.Tracing down those
ancestors can take some time, but it is possible.

The female’s X chromosome may not match her partner’s much at all or the amount of DNA shared
may be small. In those cases, the two people are likely to be distant cousins or even more distantly
related. Amanda, for example, has a match on chromosome 8 who is not her biological father. They
share only about 100kb of DNA, which means they are likely second cousins at best. They have never
met.

The genealogical research will determine whether or not the two people are related, and if so,
how closely.
The most common match is a brother and sister who both match each other on the X-chromosome
test. This is rare; in most cases, more than half of a pair of siblings don’t match each other at all. Most
of the DNA shared among siblings is shared by brothers and sisters of the same sex. Men and women
share their mother’s family line with equal frequency.

The standard test is worth only one thing: it will tell you if you share a common ancestor in the
previous four generations. That’s it.

There are many different types of X-Chromosome tests, and they vary in how much DNA they can
detect. If you purchase a DNA test from one of these companies, the results may or may not be useful
to you.

It’s much more useful to test your mother and father for their X-Chromosome matches. In many
cases, a man will have more matches than a woman; men tend to have more siblings than women do.
Generally speaking, the broader the geographical distribution of your X-matching relatives is, the older
they are likely to be.

If you want to test someone else’s DNA, I can help with that too. It’s called a Y-Chromosome test. It
will tell you nothing about your ancestry. You will not be able to trace back any father or grandfather
on the paternal line.

You will also get a more significant match if you are male and you match someone who is male than if
they match you. The same is true if you are female and match another female.

I also offer a DNA test on the Y-Chromosome that will identify male and female matches. That
information is useful if you are interested in finding a spouse.

It’s important to understand that with all DNA tests, your own DNA will not match yours. So if
you get a match for someone else, it means their ancestors must have passed through your family
line at some point. A person who shares only half of their ancestral line with you is much closer to you
than one who shares none.

For the most part, all X-DNA matches I have tested have been unbreakable ties to relatives in the
same generation or within one generation of that generation. Sometimes there are unbreakable ties to
a previous generation; again, this is the case with an equal number of maternal and paternal lines.