2023-08-23 17:16:48
Does more than twenty years we discovered a first draft of the human genome, full of “holes” representing DNA sequences that could not be obtained, with a total estimated size of three billion nucleotides – letters A, T, G and C–. This genome has been gradually revised, in successive roundsalways improving the quality of the sequence and solving most of the blank spaces that prevented a complete reading of our genetic material.
The fundamental difficulty that researchers have faced in reading the human genome from cover to cover is the enormous number of repeated sequences of all kinds that populate it. Let us remember that the approximately 20,000 genes that human beings have barely occupy 2% of the entire genome. And that the remaining 98% is fundamentally formed by those families of repeated sequences, by mobile elements (transposones and retrotransposons above all) and, to a lesser extent, but functionally very relevant, by the regulatory sequences of gene expression. The latter function as switches that determine when and where genes are turned on and off.
In March 2022 it was published in Science the major revision of the genome. A international consortium of researchers called “T2T” (from telomere to telomere, with telomeres being the ends of chromosomes) used a novel strategy based on the use of a type of cell (CHM13) that retains only one copy of each chromosome. Combining it with the latest techniques for sequencing large chunks of DNA, they managed to add some 200 million letters to the genome, resolving most of the holes in chromosomes 1 to 22.
The only one left out was the smallest of all the chromosomes that humans have: the Y chromosome. An exclusively male chromosome that is also the most complex in terms of the presence of repeated sequences of all kinds.
The Y chromosome, finally complete
Each one of us has in our cells 46 chromosomes, arranged in pairs. They are actually 23 pairs of chromosomes, 22 pairs of autosomal chromosomes (from 1 to 22) and one pair of sex chromosomes (which can be X or Y).
From each pair of chromosomes we inherit one from our father and the other from our mother. Most women have the 46XX chromosome configuration, meaning the last pair of chromosomes, 23, is made up of two copies of the X chromosome. Most men have the 46XY chromosome configuration, which means that the pair The sex chromosome consists of an X chromosome and a Y chromosome.
The Y chromosome cannot have genes that are essential for everyone, since it is only present in males. What it does have are the genes responsible for the development of the male sexual organs, in particular the master gene SRY, which unleashes a cascade of events that ends up converting an initial undifferentiated gonad into the testicles, where sperm are produced. In the absence of the gene SRY (as in 46XX women), that primordial gonad eventually becomes the ovaries, where the ova are produced.
The T2T consortium has just solved the technical problems that prevented the completion of the Y chromosome sequence. And now presents to us, in an article in the magazine Naturethe more than 62 million letters it contains, adding an additional 30 million letters to the length of the total human genome, which would now be 3.23 billion letters, with recent updates.
They have also discovered 40 additional genes that encode proteins that we did not know about, as they are hidden in areas that could not be read. The new reference genome is called T2T-CHM13+Y and has been made available to the entire research community by the authors of the study.
There is more than one genome: the pangenome initiative
This new contribution to the knowledge of our genome must coexist with the pan genome initiative, which we met a few months ago, and which aims to collect the existing genetic variability among human beings. Because, although we share a large part of our genome, we all differ by approximately 0.1%, which corresponds to more than 3 million different pairs of letters between any two people.
With the pangenome we will no longer have a single reference genome, but hundreds of human genomes that will more reliably illustrate our genetic similarities and differences. This should help, among other things, to more easily detect gene mutations associated with the thousands of congenital diseases that we know of.
Well, together with the complete sequence of the Y chromosome, the magazine Nature publish today in a second study the sequences of 43 Y chromosomes derived from humans who lived in the last 183,000 years. Their analysis reveals great diversity in both the size and structure of this Y chromosome throughout evolution. The researchers have detected, among other things, large sequence inversions: pieces of DNA that are turned around and inserted upside down.
The greatness of deciphering the smallest chromosome
That we know more about the Y chromosome is great news. It is enough to remember that, approximately a year ago, we witnessed another scientific advance that correlated the usual loss of the Y chromosome in many cells with lower life expectancy for men compared to women. And it is clear that much more valuable information is hidden in their genes.
With these two new studies, our knowledge of human DNA is significantly increased, solving how much we still needed to discover about the smallest but most complex chromosome in our genome.
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