Characterisation of the 3' region of the PSG11 gene : a thesis presented in partial fulfilment of the requirements for the degree of Master of Science in Genetics at Massey University, Palmerston North, New Zealand

Abstract

Appendix : Content removed due to copyright restrictions. 1. Bichimica et Biophysica Acta l2l9 (1994) 195-t97 Sequence of a novel pregnancy-specific B,-glycoprotein C-terminal domain Terence W. Joe, Patricia A. McLenachan. Brian C. Mansfield 2. GENOMICS 22, 356-363 (1994) Characterization of the PSG11 Gene P. A. McLenachan,* K. J Rutherfurd* K. T. Beggs S.E. Sims,* B. C. Mansfield 3. Evolutionary Analysis of the Multi-gene Pregnancy-specific B1-glycoprotein Family: Separation of Historical and Non-historical Signals. Patricia A. McLenachan*, Peter J. Lockhart, H. Rick Faber*, Mansfield [accepted manuscript]The pregnancy-specific beta-1 glycoproteins (PSG) are a family of abundant proteins essential to pregnancy that are encoded by 11 genes located on chromosome 19q 13.1-13.3. The genes can be divided into three subgroups based on the organisation of their 3' coding regions. In 1989, our group isolated cosmid hC3.11, which contained most of the PSG11 gene, but which did not include the 3' coding region. This thesis reports subsequent work to characterise two further cosmids which span the PSG11 locus and which do include the 3' coding region. These cosmids were mapped and partially sequenced Three exons encoding potential alternative C-terminal domains were identified: Cw, Cr and Cs. The Cs domain lies 4.6kb from the end of the B2 domain. This is the first report of genomic sequence for this particular domain and for a functional PSG subgroup 3 gene. Downstream from this exon are sequences homologous to the C-termini of subgroup 1 PSG genes This finding suggests that subgroup 1,2 and 3 genes are related via insertion/deletion events. Data from seven PSG genes from all three subgroups and from four different regions were used to construct evolutionary trees. Variability patterns in the data were examined and these showed that the mechanism of sequence evolution for the N-terminal domain, the A1 domain, and to a certain extent, the B2 domain was not neutral Sequences from these regions were shown to be unsuitable for determining historical relationships between PSG genes. In contrast, the data from the C-terminal region showed a better fit with the assumptions of sequence evolution (e.g. all changes are independent and identically distributed) required by currently implemented analysis methods. Evolutionary tree reconstruction using this region gave a phylogeny that was consistent with one based on the genomic organisation of the genes