Washington, June 2 : Researchers in Turkey have found that genetic mutations are responsible for humans walking upright, and not on all fours.
A research team led by Professor Tayfun Ozcelik, of Bilkent University, Ankara, Turkey, studied unrelated quadrupedal families discovered in 2005 where some members were affected by the rare quadrupedic condition, Unertan syndrome, also linked with imperfect articulation of speech, mental retardation, and defects in the cerebellum, a part of the brain involved in motor control.
It was found that the affected individuals in two families had mutations in the gene responsible for the expression of very low density lipoprotein receptor (VLDLR), a protein which is known to be critical to the proper functioning of the cerebellum during development. Also, the scientists could not find a single genetic mutation implicated in the condition in different families living in isolated villages 200-300 km apart without any ancestral relationships.
"We carried out genome-wide screening on these families 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," said Professor Ozcelik.
He added: "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."
It was found that in all cases, the affected individuals were the offspring of consanguineous marriages, indicating that they would not have had the condition if in case they had married outside the family. 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 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," said Professor Ozcelik.
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. 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," said Professor Ozcelik.
The researchers also found mutations causing VLDLR deficiency in Hutterites, a group of Anabaptists who live in colonies of North America, where the majority of the affected individuals cannot walk at all. As most of the neurological characteristics of the affected members of the Turkish families and the Hutterites were found to be similar except that the Turkish individuals are able to walk on all fours. This led the scientists to predict that the Hutterites may be more profoundly affected due to the deficiency in VLDLR and a neighbouring gene, and therefore lack the motor skills even for quadrupedal locomotion.
Upright walking is also one of the traits other than brain enlargement, speech, and the ability to make tools, that have led to modern humans. And now the researchers have shown 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," said Ozcelik.
The details of the study will be presented to the annual conference of the European Society of Human Genetics.