All,
Given the heated debates (in the literature as well as on the WEB) that were generated by the initial, controversial reports on the nature of the diminutive Liang Bua human being(s), I find it curious that the some of the conclusions of the following papers have yet to be extensively discussed by the main actors in the Liang Bua saga
The papers I am referring to are:
Elen Griffith, Sarah Walker, Carol-Anne Martin, Paola Vagnarelli, Tom Stiff, Bertrand Vernay, Nouriy Al Sanna, Anand Saggar, Ben Hamel, William C Earnshaw, Penny A Jeggo, Andrew P Jackson, and Mark O’Driscoll. Mutations in pericentrin cause Seckel syndrome with defective ATR-dependent DNA damage signaling. 2008. Nature Genetics 40 (2): 232-236.
Abstract:
Large brain size is one of the defining characteristics of modern humans. Seckel syndrome (MIM 210600), a disorder of markedly reduced brain and body size, is associated with defective ATR-dependent DNA damage signaling. Only a single hypomorphic mutation of ATR has been identified in this genetically heterogeneous condition. We now report that mutations in the gene encoding pericentrin (PCNT)—resulting in the loss of pericentrin from the centrosome, where it has key functions anchoring both structural and regulatory proteins—also cause Seckel syndrome. Furthermore, we find that cells of individuals with Seckel syndrome due to mutations in PCNT (PCNT-Seckel) have defects in ATR-dependent checkpoint signaling, providing the first evidence linking a structural centrosomal protein with DNA damage signaling. These findings also suggest that other known microcephaly genes implicated in either DNA repair responses or centrosomal function may act in common developmental pathways determining human brain and body size.
Anita Rauch, Christian T. Thiel, Detlev Schindler, Ursula Wick, Yanick J. Crow, Arif B. Ekici, Anthonie J. van Essen, Timm O. Goecke, Lihadh Al-Gazali, Krystyna H. Chrzanowska, Christiane Zweier, Han G. Brunner,8 Kristin Becker, Cynthia J. Curry, Bruno Dallapiccola, Koenraad Devriendt, Arnd Dörfler, Esther Kinning, André Megarbane, Peter Meinecke, Robert K. Semple, Stephanie Spranger, Annick Toutain, Richard C. Trembath, Egbert Voss, Louise Wilson, Raoul Hennekam, Francis de Zegher, Helmut-Günther Dörr, and André Reis. 2008. Mutations in the Pericentrin (PCNT) Gene Cause Primordial Dwarfism. Sciencexpress /www.sciencexpress.org/ 3 January 2008 / Page 1 / 10.1126/science.1151174.
Abstract:
Fundamental processes influencing human growth can be revealed by studying extreme short stature. Using genetic linkage analysis, we find that biallelic loss-of-function mutations in the centrosomal pericentrin (PCNT) gene on chromosome 21q22.3 cause microcephalic osteodysplastic primordial dwarfism type II (MOPD II) in 25 patients. Adults with this rare inherited condition have an average height of 100 centimeters and a brain size comparable to that of a 3-month-old baby, but are of near-normal intelligence. Absence of PCNT results in disorganized mitotic spindles and missegregation of chromosomes. Mutations in related genes are known to cause primary microcephaly (MCPH1, CDK5RAP2, ASPM, CENPJ).
It is worth noting that both papers do make reference – albeit briefly – to the possibility that this work on the Pericentrin gene could possibly serve to explain the physical characteristics of Homo floresiensis and that of its putative predecessors:
There is an ongoing debate as to whether the Late Pleistocene hominid fossils from the island of Flores, Indonesia, represent a diminutive, small-brained new species, Homo floresiensis, or pathological modern humans.
We note that individuals with MOPD II have several features in common with Homo floresiensis, including an adult height of 100 cm, grossly normal intelligence despite severely restricted brain size, absence of a sloping microcephalic morphology, and a number of minor morphological features including facial asymmetry, small chin, abnormal teeth, and subtle bony anomalies of the hand and wrist. Given these similarities, it is tempting to hypothesize that the Indonesian diminutive hominids were in fact humans with MOPD II. With the identification of the genetic basis of MOPD II, this hypothesis may soon be testable. (Rauch et al, p. 3.)
Morphologically, Seckel syndrome also has evolutionary parallels. Homo floresiensis, the recently described Indonesian hominid, has similarly marked reduced brain and body size (cranial volume –6.1 s.d, height –9.5 s.d, relative to modern humans). Consequently, changes in PCNT or similar genes could underlie the anatomical differences seen in this hominid. (Griffith et al, p. 235).
Jacques
