How many chromosomes do you have?

The story of one mutation

Alexander Sokolov, XX2 century

One of the popular arguments of creationists sounds like this: apes – chimpanzees, gorillas and orangutans – have 2 more chromosomes than humans. How did it happen that in the process of evolution, people lost their chromosomes? Is something like this happening in our country now? Why can people not even suspect that they are mutants? How do these mutants reproduce?

Let us remind our dear readers that chromosomes are such things in which DNA is packed in our cells. A person has 23 pairs of chromosomes: 23 chromosomes came to us from mom and 23 from dad. Total 46. In chimpanzees – 24 +24 = 48. A complete set of chromosomes is called a "karyotype". In each chromosome there is a very large DNA molecule in a tightly twisted form. In fact, it is not the number of chromosomes that is important, but the genes that these chromosomes contain. The same set of genes can be packed into different numbers of chromosomes.

In 1980, an article by a team of geneticists from the University of Minneapolis was published in the authoritative journal Science. The researchers applied the latest methods of chromosome coloring at that time (transverse stripes of different thickness and brightness appear on the chromosomes, while each chromosome has its own special set of stripes). It turned out that in humans and chimpanzees, the striation of chromosomes is almost identical! But what about the extra chromosome in monkeys? It's very simple: if you put the 12th and 13th chromosomes of a chimpanzee in one line opposite the second human chromosome, connecting their ends, we will see that together they make up the second human one.

Comparison of human and chimpanzee chromosomes. It can be seen that the 2nd chromosome of a human corresponds to the 2nd chromosomes of a chimpanzee. Source: Jorge Yunis, Diagram of human and chimp chromosome, Science 208:1145-58 (1980). Courtesy of Science magazine.

Later, in 1991, scientists took a closer look at the point of the alleged fusion on the second human chromosome and found there what they were looking for – DNA sequences characteristic of telomeres – the end sections of chromosomes. A year later, traces of the second centromere were found on the same chromosome (the centromere is the site necessary for normal cell division. The centromere usually divides the chromosome into two parts called arms; each chromosome has only one active centromere). Obviously, there used to be two chromosomes in place of one. So, once our ancestors had two chromosomes merged into one, forming the 2nd human chromosome.

How long ago did this happen? Now that paleogeneticists have learned how to reconstruct the genomes of fossil creatures, we know that both the Neanderthal and the Denisovan man had 46 chromosomes several tens of thousands of years ago, just like us. According to modern data, the merger occurred much earlier, in the range of 2.5–4.5 million years ago. In order to determine the date more precisely, it would be good to get the genomes of the Heidelberg man and Homo erectus, as well as completely reconstruct the corresponding chromosomes of modern great apes.

But the question arises: let's say one of our ancestors has two chromosomes combined into one. He got an odd number of chromosomes – 47, while the rest of the non–mutated individuals still have 48! And how did such a mutant then reproduce? How can individuals with different numbers of chromosomes interbreed at all? Let me remind you that during meiosis – cell division, as a result of which germ cells are formed – each chromosome in the cell must connect with its homologue pair. And then there was an unpaired chromosome! Where should she go?

But it turns out that this is not a problem if homologous sections of chromosomes find each other during meiosis. In the case of an odd number of chromosomes, some germ cells may carry an "unbalanced" genetic set due to incorrect chromosome divergence in meiosis, but others may turn out to be quite normal.

When crossing a 47-chromosomal mutant with a 48-chromosomal "wild" individual, part of the children will turn out to be ordinary, 48-chromosomal (24 + 24), and part - 47-chromosomal (23 from the mutant parent + 24 from the usual one). As a result, there are already several individuals with an odd number of chromosomes. It remains for them to meet – and voila: 46 chromosomes (23 +23) appear in the next generation. Experts believe that the further spread of the 46-chromosome type could have occurred due to some evolutionary advantages resulting from this mutation. The fusion of chromosomes led to the loss or change in the work of genes located near the point of fusion. Maybe because of this, fertility has increased or cognitive abilities have increased (studies show that several genes located near the point of fusion of chromosomes are expressed in the brain, as well as in the sex glands of men).

A model of a "gorilla-like" polygamous clan of early Homo, where a male (or male) had a fusion of chromosomes. Squares are males, circles are females.

The male with the mutation (II generation), the owner of 47 chromosomes, had children from several females (III generation). As a result, some of his descendants turned out to be 48-chromosomal (unpainted), some – 47-chromosomal (half-painted), in addition to the sick and dead due to the imbalance of chromosomes (black triangles). In the IV generation, as a result of crossing two carriers of the mutation, 46-chromosomal variants are obtained (a completely colored circle and square).

Someone will say that all this is fantasy. However, the fusion of chromosomes occurs in humans even now, as a result of a common mutation – Robertson translocation (abbreviated as ROB).

If you have seen a chromosome in the picture, then imagine that it often looks like two "arms" extending from one point – (this point is the centromere). Sometimes the shoulders are the same length – such a chromosome is called metacentric. If the shoulders are unequal, the chromosome is submetacentric. And if one of the shoulders is so short that it is almost invisible, the chromosome is acrocentric.

So, with ROB, two acrocentric chromosomes break at the centromere point, and their long arms merge, forming a new single chromosome. The short arms also connect and form a small chromosome, which is usually lost in a few cell divisions. So it became one chromosome less. At the same time, a small chromosome contains so little genetic material that it can disappear without any noticeable effect for the individual. Everything would be fine, only the body got an odd set of chromosomes (22 +23 = 45 instead of 46).

Robertson translocations are not such a rare event. 45 chromosomes are found in every 1000th newborn baby. In humans, ROB can affect acrocentric chromosomes 13, 14, 15, 21 and 22. Most ROB carriers are absolutely healthy and do not suspect anything until they try to have children. But problems may not arise – and in this case, the mutation will be passed from generation to generation, unnoticed by anyone.

And what is the chance for two such mutants to meet and give birth to a 44-chromosome baby? It would seem that this is a very unlikely event. However, in small human populations, marriages between relatives – for example, cousins – are not uncommon. In this case, crossing two ROB carriers is quite possible. Such stories have been known to geneticists for many decades. Here are just two of them.

The fact of mutation transmission for at least 9 generations was recorded in 1987. ROB were found in three Finnish families dating back to a common ancestor. The genealogy of the families was traced back to the beginning of the XVIII century, when their ancestors lived in 3 villages in the north of present-day Finland, not far from each other. The largest of the families contained at least 49 carriers of fused chromosomes 13 and 14 at the time of the study. Among them there was also a homozygote by mutation, the owner of 44 chromosomes – a woman whose parents were second cousins. Except for her small height, 152 cm, she was healthy and gave birth to 6 children! An amazing woman died at the age of 63 from cardiac arrest.

Another case was recorded in 2016 in China. The story is as follows: a 25-year-old Chinese man married a young woman; they had a son, but died 6 months old. In this regard, doctors made a genetic analysis. It turned out that the deceased child was 45-chromosomal, the mother was ordinary, but the father was the owner of 44 chromosomes. Further investigation revealed that the man's parents are cousins, both carriers of ROB. They have merged into one chromosome 14 and 15. The specialists decided to conduct a full examination of a unique patient. To begin with, he was examined by a psychiatrist and a neurologist, who did not reveal any deviations from the norm. Then the man had a brain tomogram, an electroencephalogram and even a lumbar puncture – everything is fine, the "mutant" is healthy as a bull. Next, the scientists studied the spermatozoa of both the man himself (44 chromosomes) and his father (45 chromosomes). In the father, 20% of the sperm were unbalanced, but in the son, 99.7% of the sperm were quite normal. So, our 44-chromosomal man is healthy and ready to reproduce. Of course, as we can see, when married to a woman with a normal karyotype, he had difficulties. But if he got a ROB-homozygote like him, everything would be perfect.

According to the authors of the study, the reproductive barrier between ROB carriers and ordinary people, theoretically, can lead to the formation of an isolated population of 44-chromosomal people interbreeding with each other. And this is the way to the emergence of a new subspecies of Homo sapiens.

Comment by PhD, Head of the Laboratory of Comparative Genomics at the Institute of Molecular and Cellular Biology SB RAS Vladimir Trifonov:
The fact that the genome, like any biological system, is dynamic and changeable, has been known for a very long time, and the enumeration of evidence of these changes obtained by sequencing methods will take hundreds of years. The variability of the genome can manifest itself at different levels – these are substitutions of individual DNA nucleotides, their insertions and deletions, and changes in slightly longer sections (for example, mobile elements are inserted very often), and, finally, large chromosomal rearrangements visible even in a microscope, and therefore attention to them has long been increased. In some organisms, variability may even include an increase in the number of genomes per cell (ploidy), especially often such changes occur in plants, especially cultivated ones. So in the question of genomic differences between humans and great apes, researchers are surprised not by the presence of chromosomal rearrangements (in fact, of course, there are much more of them, just chromosome 2 is most noticeable in a microscope), but why there are so few of them. Most other mammalian species have undergone more significant genomic transformations over the same period of time, how did they not displace our ancestors with less agile genomes?
The question of how mutations, which include chromosomal rearrangements, are fixed in a population was solved by the creators of the synthetic theory of evolution at the beginning of the last century, and this question is described in the same textbook of general biology. Therefore, references to different numbers of chromosomes as a kind of contradiction are certainly an indicator of ignorance and lack of elementary school knowledge.

Literature

1. Eklund A, Simola KO, Ryynänen M. Translocation t(13;14) in nine generations with a case of translocation homozygosity // Clin Genet. 1988; 33:83–6.
2. Jieping Song et al. A family with Robertsonian translocation: a potential mechanism of speciation in humans // Molecular Cytogenetics 2016 9:48 DOI: 10.1186/s13039-016-0255-7
3. Stankiewicz P. One pedigree we all may have come from – did Adam and Eve have the chromosome 2 fusion? // Molecular Cytogenetics 2016 9:72 DOI: 10.1186/s13039-016-0283-3
4. Yunis JJ, Sawyer JR, Dunham K. The striking resemblance of high-resolution G-banded chromosomes of man and chimpanzee // Science. 1980 Jun 6;208(4448):1145-8
5. Avarello R et al. Evidence for an ancestral alphoid domain on the long arm of human chromosome 2 // Hum Genet. 1992 May;89(2):247-9

Portal "Eternal youth" http://vechnayamolodost.ru  19.12.2016