In 2005, scientists discovered a few families in Hungary where some of the adults only walked on all fours. Few understood the causes of this rare condition, called Unertan syndrome. Some scientists speculated that the quadrupedal people had simply never learned to walk upright due to learning disabilities and lack of access to proper medical care. Others believed that these families had a mutation in a set of genes that cause humans to walk upright. Today at a conference, researchers in Turkey are presenting the results of a study where they analyzed the genomes in all four families. They are beginning to figure out what causes present-day humans to walk on all fours the way our distant ancestors did.
All four families have a few things in common. First, the people with Unertan syndrome are all the products of incestuous marriages. Children of closely-related people often suffer birth defects. Also, the children who walk on all fours are developmentally disabled; some are unable to talk. What shocked the researchers was that the families with quadrupedal members did not share the same kinds of genetic mutations. One of the researchers, Tayfun Ozcelik, gave a talk today at the European Society of Human Genetics about the genetic study. According to a release from the Society:
Although the families lived in isolated villages 200-300 km apart and reported no ancestral relationships, the scientists expected to find a single genetic mutation implicated in the condition. They were surprised to find that this was not the case.
"We carried out genome-wide screening on these families", said Professor Ozcelik, "and found regions of DNA that were shared by all those family members who walk on all fours. However, we were surprised to find that genes on three different chromosomes are responsible for the condition in four different families.
"In families A and D there were mutations in VLDLR on chromosome 9, and in family B the phenotype maps to chromosome 17 to a region that contains at least 157 genes, and we are still looking for the precise mutation. Neither region appears to be implicated for family C."
In all cases, the affected individuals were the offspring of consanguineous marriages, which suggests that if they had married outside the family they would not have had the condition. All of them had significant developmental delay in infancy. "Whereas normal infants make the transition to walking on two legs in a relatively short period", said Professor Ozcelik, "these individuals continued to move on their palms and feet and never walked upright. Although they can stand from a sitting position and maintain this upright position with flexed hips and knees, they virtually never initiate bipedal walking on their own."
It has been suggested in the past that lack of access to medical care exacerbated the effects of an under-developed cerebellum, and that this led to quadrupedality. "Although it may be true that family B lacked proper medical care, families A and D had consistent access to good medical attention, and both families sought a correction of quadrupedality in their affected children", said Professor Ozcelik. "Indeed, an unaffected member of family A is a physician, who has been actively involved in the medical interventions. In addition, the parents in family A also discouraged their affected children from walking on all fours, to no avail. We think that social factors are unlikely to be involved in the development of quadrupedal locomotion."
Along with brain enlargement, speech, and the ability to make tools, upright walking has long been regarded as one of the key traits that have led to modern humans. Professor Ozcelik's team have opened a window on how mutations in VLDLR affect brain development and influence gait in humans.
"It will be interesting to see if the VLDLR gene is involved in other types of cerebellar ataxias. In addition, we hope to identify the defective genes associated with quadrupedal locomotion in families B and C", he says.
All the families do share genetic factors in common, and Ozcelik's team says similar genetic factors are found in a few North American families whose members cannot walk at all.
If it turns out that there are several groups of genes that control for bipedalism, it might be possible to genetically modify people to walk on all fours. It's hard to imagine why anyone would want to do this outside a mad scientist movie. However, many human genes are shared with our quadrupedal mammalian cousins. Perhaps discovery of the bipedal gene could be the first step in helping cats, dogs, and apes to walk upright. Yes, it could be the first key to "uplifting" other species.
Genetic Mutation Linked to Walking on All Fours [Eurekalert]