A mystery that lasted for more than 100 years has been solved: Why can life continue to evolve?

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More than 100 years ago, geneticists discovered the phenomenon of chromosome recombination in germ cells. This is like a slow but steady way of evolution, making the genome more diverse through each generation of organisms. But even an abnormality in a base can cause disease. Until recently, scientists have figured out how organisms precisely control this process.

Written by Shi Yunlei

Proofread by Wu Fei

Advantages of sexual reproduction

Hermann Joseph Muller, one of the most influential geneticists of the 20th century and a Nobel Prize winner, once proposed a theory called Muller's ratchet. As a scientist who used X-rays to study gene mutations, he said that sexual reproduction has a great advantage over asexual reproduction: sexually reproducing organisms undergo a process called meiosis when producing gametes, which can help organisms repair severe DNA damage.

Hermann Joseph Mahler (Photo source: Nobel Prize official website)

In this process, the chromosomes will be replicated once, and then the cell will divide twice, that is, one mother cell will eventually produce 4 daughter cells. During the first division, the chromosomes from the two parents in the mother cell will pair up with each other, and they are homologous chromosomes. If a chromosome has both strands damaged, the damage can be repaired by exchange and recombination between chromosomes. In asexual organisms, since recombination cannot be performed, gene mutations caused by DNA damage and other conditions will continue to accumulate, eventually leading to the death of the organism. (Of course, later studies have confirmed that some organisms that reproduce asexually, such as bacteria, can also effectively repair DNA damage in other ways, so Mahler's view may not be correct.)

During meiosis, recombination occurs between homologous chromosomes. (Image source: Wikipedia)

Mahler proposed this view, which was related to the genetic research conducted by Thomas Hunt Morgan, the founder of the genetic theory, using fruit flies. In 1916, he also noticed that in fruit flies, the exchange of fragments between chromosomes with similar genetic composition and capable of pairing with each other was not only to repair damaged genes, but also to carry out genetic recombination, so that the genetic composition of each offspring was different. However, the scientific community has not been completely clear about the specific mechanism of genetic recombination.

Each generation is evolving

Gene mutation and gene recombination can promote species evolution. For bacteria and viruses, they have strong reproductive capacity and can evolve through rapid gene mutation when facing external pressure. After being screened by external pressure, a population may only have a few mutant strains left, but due to their efficient reproductive capacity, these mutant strains quickly form a new population.

Gene mutations also exist in multicellular organisms, but for them, evolution through mutation is not a very reasonable and efficient way. For example, the human body uses various methods to repair gene mutations and damage. Existing studies have found that many gene mutations are associated with various developmental defects, cancers and other diseases. For sexually reproducing organisms, expanding the genetic diversity of offspring through gene recombination is a stable and effective way, although slow. In this process, a common question is why can two homologous chromosomes accurately exchange fragments of the same size?

It is conceivable that if the exchanged gene fragments are not equal, it will lead to a disaster. A common example is chromosome translocation (the fragments of non-homologous chromosomes are rearranged and combined, and the length of chromosomes is changed after exchange). This process may cause chromosome loss in the fetus, and even lead to various abnormalities such as miscarriage. Since the genes involved in the sexual reproduction process are conserved in organisms, some scientists try to answer this question by studying some simpler organisms to advance the understanding of the evolution and development of various organisms. And the answer this time is a plant that reproduces sexually.

A special plant

Arabidopsis thaliana is a tiny plant with a small genome, just five pairs of chromosomes, and a typical selfing plant (sexual reproduction). Like its predecessor, the pea plant that Mendel used to discover the laws of genetics, this plant was destined to change people's understanding of plant biology and genetics.

The growth process of Arabidopsis thaliana (Image source: https://elifesciences.org/articles/06100)

In 2012, scientists at the Jean-Pierre Bourgin Institute in France discovered a new protein, HEI10 (a ubiquitin ligase), based on previous research. It belongs to a class of proteins called ZMM. The latter is mainly responsible for regulating the exchange of gene segments on homologous chromosomes during meiosis. Previous studies have found that various proteins in this class have different divisions of labor: some proteins are responsible for pulling the two chromosomes closer and maintaining a stable structure, while others promote DNA recombination.

There is a hypothesis that the function of HEI10 protein will be different. Its number on chromosomes can affect the number of times chromosomes undergo recombination, or can control the site where chromosome recombination occurs. Recently, in an article published in Nature Communications, researchers from the University of Cambridge used ultra-high-resolution microscopy and mathematical models to study the behavior of HEI10 protein on chromosomes of Arabidopsis during meiosis in order to verify this hypothesis.

During chromosome recombination, HEI10 protein moved from hundreds of small aggregates at the beginning to only a few sites at the end. (Image from the paper)

They found that at the beginning, HEI10 protein would treat chromosomes as a track and move randomly on it, forming many small protein aggregates. As time passed, HEI10 protein moved to the site where homologous chromosomes formed a synaptonemal complex. After this structure was formed, chromosomes would exchange with each other. HEI10 protein would be fixed when it moved to this position, and then more and more HEI10 protein would be enriched at the same location. In the end, hundreds of small aggregates composed of HEI10 protein at the beginning became large aggregates in the single digit. At these sites where HEI10 protein is most enriched, chromosomes will undergo crossover and recombination.

When the expression of HEI10 protein in plants is increased, the number of sites where chromosome recombination occurs in cells increases, and the distance between recombination sites becomes closer. When the amount of HEI10 protein in cells is reduced by 40%, only one synaptonemal complex region of homologous chromosomes will undergo genetic recombination. The researchers believe that the synaptonemal complex region of the cell is a candidate site for chromosome exchange, and the amount of HEI10 protein accumulated at the site determines whether genetic recombination occurs.

Found in many organisms

This pattern of genetic recombination is conserved in many organisms, including yeast, nematodes, fruit flies, and mammals. Previously, in a study published in Nature Genetics, Professor Neil Hunter of the Howard Hughes Medical Institute and others found that when the HEI10 protein was lacking, the early stages of chromosome recombination in mice could proceed smoothly, but chromosome recombination would not occur in the end. In other words, the HEI10 protein plays a decisive role in the later stages of this process.

All these lives come from a fertilized egg, and the genome in this initial cell also determines the genome composition of each cell that makes up the individual organism. Whether it is the repair of base mutations in genes, expression, or gene recombination, it all needs to be precisely regulated in order for life to exist and continue. However, genes are also very fragile. Many environmental factors can not only affect the genes, illnesses, and lifespan of the parents, but can also affect the offspring through gene transmission.

That is to say, some bad living environments (air pollutants, ultraviolet rays, heavy metals and stress, etc.) and living habits (alcoholism, smoking and eating a lot of junk food) are not only affecting our own health, but may also be changing our most basic genes. With the development of biotechnology in the future, some of the harmful effects may be eliminated. But today, each of us has a healthy body, perhaps thanks to the relatives in the family tree, as well as the various cells and molecules in the body that are always working hard.

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