Why We Lack Spare Ribs: The Evolution of the Human

July 17, 2003 — University of Utah researchers have identified genes that help explain why mice, humans and other mammals evolved with modern skeletons instead of having elongated bones like snakes. the neck to the tailbone.

By genetic restriction, the doctor Mario Capecchi and Deneen Wellik fed the female postdoctoral mice with other ribs that start below the normal chest and continue down to the bottom and the tail.

The new study provides a more complete scientific picture of how 16 key genes — all of which evolved from a single gene in ancient spineless animals — help develop the right hands and feet. the lowest in vertebrates, which are animals with spines.

“What we have shown is a specific ancestral set of genes that are used to build the legs as well as your lower body skeleton [below the ribs],” said Capecchi, professor and the chair of genetics at the University of Utah and an investigator at the Howard Hughes Medical Institute.

The study, published July 18 in the journal Science, sheds new light on “how we are united and how we differ from other forms of life,” said Capecchi.

During the evolution of carnivores, the ancestral genes found new uses, including suppressing the development of other bones, which allowed the animals to move and be more flexible to hunt. or run away from it.

“At first, your [early vertebrate] skeleton was protecting and keeping your body rigid, making it harder for someone to land on you and eat you,” Capecchi said.

According to Wellik, the genes that suppress the bones and allow the development of sacral vertebrae – which attach the pelvis to the spine – made it possible to improve the development of mammals.

Capecchi is widely known among geneticists for the development of the “gene model” in mice.

In the new study, Welik and Capecchi studied the “homeobox” or “Hox” genes, which control the activity of other genes to make an embryo grow into an adult.

Up to 13 Hox genes control the development of their embryos.

The first fish and other predators evolved from a common invertebrate ancestor.

When ancient mammals evolved, they had four sets of 13 Hox genes, or a total of 52 on four chromosomes.

But the proliferation of new Hox genes is thought to have allowed the rapid evolution of vertebrates.

Some of the 52 Hox genes were redundant and eventually disappeared from the genetic makeup, so humans, mice and all other animals now have 13 groups of Hox genes with two to four genes in each group, for a total of 39 Hox genes.

Since the first 13 Hox genes in invertebrates were cloned in mammals, genes in any group of related gene clusters overlap in what they do, including many also found new jobs.

To determine what a group of Hox genes do, two to four of each group must be paralyzed to show their normal function.

Capecchi and Wellik studied two groups of Hox genes – Hox10 and Hox11 – and their role in skeletal development in the mouse and, consequently, in humans and other mammals.

Any animal with a bone has different types of vertebrae that make up the spine.

Rats have seven bones or necks; 13 sternum or breastbones, to which the ribs are attached; six lumbar or lower spine; four sacral vertebrae, to which the pelvis is attached; and different numbers of caudal vertebrae in the tail.

(Humans have seven neck bones, 12 chest and ribs, five lower back bones, five pelvic bones and three to five tail bones.

But some early vertebrates – early fish, amphibians and dinosaurs – had ribs growing from the bones from the neck to the chest and lower extremities. even the tail.

So how did mammals develop a lower, pelvic and tailbone without bones?

“Hox genes have been used to change the body’s basic plan to develop different body plans,” Capecchi said.

He and Welik bred mice with defects in all three Hox10 genes, called Hoxa10, Hoxc10 and Hoxd10.

“When the entire family of Hox10 genes was knocked out, the mice had bones from normal bones all the way to the tailbone,” Capecchi said.

If all of the Hox10 genes were disabled, the mice showed abnormalities, but not all of the ribs.

It shows how all the Hox10 genes share the function of preventing bones from growing out of the lumbar and pelvic bones.

When the researchers knocked out the Hox11 genes – Hoxa11, Hoxc11 and Hoxd11 – “no sacral vertebrae develop, but instead you have lumbar vertebrae all the way to the tail,” nothing It attaches the pelvis to the spine, Capecchi said.

Although the new study did not investigate the question, Capecchi suspects that other Hox genes are involved in preventing the fusion of the bones attached to the cervical vertebrae, or neck bones.

How Hox genes help build branches

Animal leg bones fall into three stages.

The hind legs include the leg or back, the lower leg and the upper leg.

The new study showed that the upper limb failed to form properly – with a short femur or hip and no knee – in mice when all the Hox10 genes were knocked out.

Wellik and Capecchi also found that when the Hox11 gene stopped working, the lower leg was deformed, with the tibia (shinbone) and fibula (cow bone) being very shortened.

Capecchi said that the new study adds to the picture of how Hox genes help in the formation of the legs in mice and – because the genes are the same in all mammals – in humans: – The formation of the upper arms is appears to be controlled by the Hoxa10 and Hoxd10 genes (new study) and the Hoxa9 and Hoxd9 genes (previous study by others).— Hand development depends in Hoxa11 and Hoxd11 (early work by Capecchi).— Forepaw or hand formation is controlled by Hoxa13 and Hoxd13 (study by others). legs are formed under the control of all Hox10 genes (the new study).— Lower limbs develop under the control of all Hox11 genes (also and the new study).— Legs or hind legs appear due to Hoxa13 and Hoxd13. genes, just like forelegs or arms (early research on other things).

According to Wellik, the Hox9, Hox10, Hox11, Hox12 and Hox13 genes in mammals – 16 of the 39 Hox genes found in all mammals – are all linked to the ancestral gene. one in invertebrates, indicating that they played an important role in allowing vertebrate evolution.