 A team of scientists in Bilkent University's "Department of Molecular Biology and Genetics" have identified the first gene implicated in the upright walking of humans. The study, which was published on-line in the "Proceedings of the National Academy of Sciences" (PNAS), USA, reports that the gene encoding the very low density lipoprotein receptor (VLDLR) has undergone mutation in two families in which multiple relatives walk by quadrupedal gait.
Two years ago, Professor Üner Tan, a neurophysiologist at Çukurova University in Adana, and a member of the Turkish Academy of Sciences, identified an extraordinary family in which five brothers and sisters walk naturally on all fours. This quadrupedal gait in humans, also known as Unertan syndrome, is a rare condition associated with dysarthric speech, mental retardation, and defects in the cerebellum of the brain. Discovered in a remote province of southern Turkey, the family triggered a scientific debate on whether they could provide unique insights into human evolution, possibly revealing genes and molecular pathways critical to walking on two feet. Upright walking, brain enlargement, tool making and speech are regarded as key traits that have led to modern humans. An alternative idea, suggested by some observers, was that quadrupedal walking in this family was the consequence of lack of access to proper medical care. The family and the associated controversies were presented in a BBC/NOVA documentary "The Family That Walks on All Fours." Other unrelated families with quadrupedal walking in multiple children have been identified subsequently in other parts of Turkey and in Brazil.
The genetic basis of quadrupedal walking has now been proven by Turkish geneticists, by the direct identification of the culprit gene. Professor Tayfun Özçelik at Bilkent University and colleagues from Hacettepe, Başkent and Çukurova Universities used genome-wide analytic tools to find regions of DNA shared by all members of the family who walk quadrupedally. Surprisingly, genetic mapping revealed that genes on three different chromosomes are responsible for the condition in different families. The PNAS report describes mutations in the VLDLR gene that cause the condition in two of the families. VLDLR is known to be critical to the proper function of the cerebellum during development.
Professor Mary-Claire King, an American geneticist at the University of Washington and the editor of the PNAS publication said, "Human molecular genetics in Turkey is 'on the map' with this elegant analysis." Professor King is known for major achievements such as identifying breast cancer genes, demonstrating that humans and chimpanzees are 99% genetically identical, and applying genomic sequencing to identify victims of human rights abuses.
Dr. Özçelik says, "VLDLR-deficiency in the brain and cerebellum at a key stage of development appears to lead to abnormal formation of the neural structures that are critical for gait." Given the heterogeneity of chromosome locales linked to quadrupedal gait, identification of the genes in the remaining families promises to offer new insights into neurodevelopment mechanisms mediating gait in humans.
The study was supported by grants from the Scientific and Technological Research Council of Turkey (TÜBİTAK), and the International Centre for Genetic Engineering and Biotechnology (ICGEB), in Italy. Bilkent graduate students involved in this project are: Elif Uz, Şafak Çağlayan, Emre Onat and Dr. Süleyman Gülsüner.
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