Accelerated evolution of Protocadherin11X/Y: a candidate gene-pair for cerebral asymmetry and language.

It has been argued that cerebral asymmetry (the "torque") is the characteristic that defines the human brain and that morphological findings in psychosis are consistent with a deviation in this sex-dependent dimension of brain growth. Evidence from sex chromosome aneuploidies and an association within families between sex and handedness is consistent with the presence of a determinant of cerebral asymmetry (a possible correlate of language) on the X and the Y chromosomes. During hominid evolution a 3.5 Mb translocation occurred from the ancestral X chromosome to the Y chromosome, resulting in duplication of the Protocadherin11X gene, such that it is represented on the X and Y chromosomes in man, whereas there is a single X-linked gene in other mammals. We re-date the duplicative translocation to 6 million years ago, that is, close to the chimpanzee-hominid bifurcation. Sequence comparisons with the chimpanzee, bonobo, gorilla, and orangutan indicate that in contrast to earlier purifying selection there has been accelerated change in the Protocadherin11X ectodomain as well as the Protocadherin11Y sequence in the hominid lineage since the duplication. The evolutionary sequence of events together with the prior case for an X-Y homologous gene suggests that this gene-pair is a candidate for the evolution of hominid-specific characteristics including the sexual dimorphism of cerebral asymmetry, a putative correlate of language.

Micro-phylogeographic and demographic history of Portuguese male lineages.

The clinal pattern observed for the distribution of Y-chromosome lineages in Europe is not always reflected at a geographically smaller scale. Six hundred and sixty-three male samples from the 18 administrative districts of Portugal were typed for 25 Y-chromosome biallelic and 15 microsatellite markers, in order to assess the degree of substructuring of male lineage distribution. Haplogroup frequency distributions, Analysis of Molecular Variance (AMOVA) and genetic distance analyses at both Y-SNP and Y-STR levels revealed a general genetic homogeneity of Portuguese sub-populations. The traditional division of the country in north, central and south, which is usually considered in studies addressing questions of the genetic variation distribution in Portugal, was not reflected in the Y-haplotype distribution. Instead, just one sub-region (Alentejo) stood out due to the presence of high diversity levels and a higher number of different lineages, at higher frequencies than in other regions. These results are reconciled with the historical evidence available, assuming that from prehistorical times down to the end of the medieval period this region harboured the most diverse groups of people and, because of economic depression, remained relatively isolated from recent homogenisation movements. The finding of a broadly homogeneous background for the Portuguese population has vast repercussions in forensic, epidemiological and association studies.

ProtocadherinX/Y, a candidate gene-pair for schizophrenia and schizoaffective disorder: a DHPLC investigation of genomic sequence.

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis. We examined differences in patients with schizophrenic or schizoaffective psychosis in the genomic sequence of PCDHX and PCDHY in coding and adjacent intronic sequences using denaturing high performance liquid chromatography (DHPLC). Three coding variants were detected in PCDHX and two in PCDHY. However, neither the coding variants nor the intronic polymorphisms could be related to psychosis within families. Low sequence variation suggests selective pressure against sequence change in modern humans in contrast to the structural chromosomal and sequence changes including fixed X-Y differences that occurred in this region earlier in hominid evolution. Our findings exclude sequence variation in PCDHX/Y as relevant to the aetiology of psychosis. However, we note the unusual status of this region with respect to X-inactivation. Further investigation of the epigenetic control of PCDHX/Y in relation to psychosis is warranted.