How can a tiny nematode be called beautiful and even win the Nobel Prize?

Well, before we get to know today’s protagonist

Be forewarning of insect terror_(:з」∠)_

On October 7, the Nobel Prize in Physiology or Medicine was announced . This year, the honor was awarded to Victor Ambros and Gary Ruvkun in recognition of their contributions to the field of microRNA.

Although both researchers are first-time Nobel laureates this year, their research subject, Caenorhabditis elegans , is already a regular winner. So far, a total of four Nobel Prizes have been awarded to this humble little worm.

Hmm? What is a nematode? How is it beautiful ? How did it win a Nobel Prize ?

Caenorhabditis elegans under a microscope | kdfj / wikimedia

They are everywhere

C. elegans belongs to the phylum Nematodes, which includes more than 25,000 species of invertebrates. In a suitable environment, tens of millions of nematodes may live in every square meter. In terms of individual numbers, 80% of the animals on Earth are nematodes - if animals around the world stand in a row, there are an average of four nematodes between you and the next "non-nematode" .

A root-knot nematode trying to burrow into a tomato root. William Wergin & Richard Sayre / Wikimedia

These creatures, which are rarely noticed, are the most widely distributed group in the Earth's biosphere. They can be found at the poles, in the mountains, in the deserts, and on the ocean floor. Nathan Cobb, a pioneer in American nematode taxonomy, once said that if all matter in the universe except nematodes disappeared instantly, the nematodes floating in the void would be a replica of the Earth's surface - mountains, lakes, seas, towns and villages, and even trees and animals, their outlines could probably be restored through the specific species of nematodes distributed among them.

However, nematodes are not only the strongest on the surface. In 2011, scientists discovered nematodes that feed on bacteria on the surface of a gold mine several kilometers underground in South Africa. In addition, a considerable number of nematodes are parasitic , such as the most familiar roundworms .

Diversity of the phylum Nematodes, where a is a roundworm and b is Caenorhabditis elegans | Blumenthal & Davis / Nature Genetics (2004)

Compared to the noodle roundworms that can reach 30 centimeters in length, Caenorhabditis elegans is petite, with mature individuals only 1 millimeter long, with pointed heads and tails, and a freely bendable cylinder in the middle. Its genus name, Caenorhabditis, contains the root word "rod-shaped" (rhabditis), and its species name, elegans, means "beautiful and elegant." Looking at the sinusoidal movement of Caenorhabditis elegans, you will probably understand how this "little worm" with a transparent body and no color got its name. In addition, unlike roundworms, Caenorhabditis elegans is a non-parasitic nematode .

The "elegant" way of moving forward of Caenorhabditis elegans | Bob Goldstein / wikimedia

Nematodes just lie down and walk

Although nematodes are small, they have all the organs. As an animal with three germ layers like humans, the ectoderm of Caenorhabditis elegans develops into a "syncytium" of multiple fused cells. It is this layer of structure that secretes collagen to form the "skin" covering the entire body . It is an "exoskeleton" that can shed and renew as the worm grows. This is also one of the characteristics of the phylum Nematoda, indicating that they are closely related to the phylum Arthropoda, which also sheds its skin.

The arrows show the "exoskeleton" formed by the fusion of different parts of the nematode's body. 丨wormatlas.com

Below the cortex are four muscle bands formed by the mesoderm that run through the body and are controlled by a set of interconnected nerve cells. Because of the way the muscles contract, what you see in the animated picture is actually a "bend" in the dorsal and ventral direction, so normal C. elegans always walk lying on its side .

Immunofluorescence staining technique outlines the muscle bundles of Caenorhabditis elegans丨wormbook.org

Inside the muscle is a fluid-filled pseudo-body cavity, and further inside is a straight digestive tract - behind the mouth is the pharynx with muscle cells that can crush food, and further back is the intestine; there is a small circle of ring-shaped cells in front and behind the intestine to form two "valves" that can be opened and closed, which is equivalent to the cardia (the entrance of the esophagus into the stomach) and anus in humans. The long gonads are attached to the side of the digestive tract.

A "real man" is one in a thousand

From a human perspective, the reproduction method of C. elegans is rather peculiar, with two sexes, hermaphrodites and males. In a normally growing population, most individuals are hermaphrodites : in the immature stage of development, hermaphrodites produce sperm and store it in the gonads; mature individuals produce eggs, which combine with prepared sperm to form fertilized eggs.

The internal structure of hermaphrodites丨wormatlas.org

Hermaphrodites are strictly speaking females, with a genome consisting of five pairs of autosomes and two X chromosomes. The resulting sperm and egg cells both contain a set of five autosomes and one X chromosome, so naturally most of the embryos produced after the combination are hermaphrodites (5*2+2X).

However, there is a very small probability that the fertilized egg will randomly lose an X chromosome, and it will develop into a male individual, which can be said to be a "real man" picked out of a thousand (5*2+X). Hermaphrodite self-fertilization can produce about 300 fertilized eggs, and after a male individual fertilizes a hermaphrodite, the number of offspring can exceed 1,000.

After encountering a hermaphrodite, the male has "intimate contact" with the other party and uses the fan-shaped structure of the tail to find the opening of the gonad for insemination丨Kbrugman / wikimedia

How the Nobel Prize quadruple was accomplished

The most important identity of Caenorhabditis elegans is that it is a model organism for scientific research. In the 1950s, when biological genetics research began to flourish, South African biologist Sydney Brenner made great contributions to the development of molecular biology, but then he turned his interest to the neural development mechanism of organisms. However, the human nervous system is composed of 100 billion neurons, so how can we study it? Brenner found the "special skills" of Caenorhabditis elegans.

First of all, Caenorhabditis elegans is small in size, eats simply, grows fast, and has strong vitality . After growing a layer of E. coli on the agar plate commonly used in the laboratory, put the nematodes on it, and the nematodes can happily reproduce while eating. At room temperature, they can reproduce a generation in three or four days, and their lifespan is about three weeks. The experimenters want to take a vacation? No problem . Put the plate directly into the -80℃ refrigerator to freeze it, and thaw it after going out. The nematodes are still alive and kicking. Hermaphroditic self-fertilization makes it very convenient to pass on the next generation, and the presence of males facilitates the hybridization of different genotypes.

In the middle of the petri dish is a colony of E. coli, and the black circle around it is a soil sample containing Caenorhabditis elegans (A); the nematodes that feed on bacteria are attracted by the food and drill out of the soil. These active nematode individuals are picked out for the next generation of reproduction (B)丨Antoine Barrière & Marie-Anne Félix / wormbook.org

Secondly, the simple and complete body structure of nematodes is a good starting point for research . In 1983, British scientist John Sulston studied the development process of Caenorhabditis elegans. In the era without advanced instruments, Sulston relied on observing the transparent worm body under an optical microscope to draw a development map of all the cells of the nematode - starting from the first division of the fertilized egg, each cell division of the nematode, the function and fate of each cell are completely determined. This is the world's first cell development lineage of a multicellular organism.

Using dots to represent the cell bodies of nerve cells and lines to represent the dendrites and axons of nerve cells, scientists have drawn a map of the nerve cells of nematodes | The OpenWorm

Today, almost all developmental biology textbooks mention that hermaphroditic nematodes produce 1,090 cells during development, 131 of which will initiate a normal apoptosis program and die after production, leaving only 959. In 2002, the Nobel Prize in Physiology or Medicine was awarded to three scientists, Brenner, Sulston, and Howard Robert Horvitz, for their contributions to the study of organ development regulation and programmed cell apoptosis . Nematodes have won the first prize on the Nobel Prize list.

From left to right: Brenner, Horwitz and Sulston. Unfortunately, Sulston passed away in March 2018. Nobelprize.org

Just four years later, the Nobel Prize in Physiology or Medicine was awarded to Andrew Fire and Craig Mello for their elucidation of the RNA interference mechanism in nematodes . The two discovered that the organism can detect the double-stranded RNA of pathogens from the blank control group that did not meet the expected results, and use it as a "guide" to attack the pathogen genome. Now, the RNA interference mechanism has become a common tool in biological research. Nematodes deservedly won the Nobel Prize double kill .

Martin Chalfie, one of the three winners of the 2008 Nobel Prize in Chemistry, used green fluorescent protein in his research on nematodes. Nematodes have won three Nobel Prizes .

A Caenorhabditis elegans nematode with the gene for green fluorescent protein inserted into it. | Dan Dickinson, Goldstein lab, UNC Chapel Hill

Then there is this year's Nobel Prize. The winners, Ambrose and Rufkun, studied two mutant strains of nematodes that showed abnormalities in the timing of gene activation during development. They discovered a completely new gene regulation mechanism implemented by microRNA , a previously unknown type of RNA.

We now know that the human genome encodes more than 1,000 microRNAs. Without microRNAs, cells and tissues cannot develop normally. This important discovery is inseparable from the useful model organism - nematodes.

Life is full of mysteries, like another universe. The picture shows the Caenorhabditis elegans after the cell nucleus was fluorescently stained丨queensu.ca

In fact, nematodes have a wider range of applications in biological research. In 1998, through a "preliminary experiment" of the Human Genome Project, Caenorhabditis elegans became the world's first multicellular organism to have its entire genome sequenced. As of 2012, the nematode neural network, which consists of 302 cell connections, has also completed the "connectome" determination.

The elegant Caenorhabditis elegans will continue to reveal the wonders of life mechanisms to humans.

Author: Lupin

This article comes from GuokrNature (ID: GuokrNature)