Walter F. Bodmer

GENETICS OF “4” AND “LA” HUMAN LEUKOCYTE GROUPS*

The possible significance of leukocyte antigens for human histocompatibility typing underlines the need to establish the genetic determination of these antigen systems. The analysis of the pairwise associations of the reactions of a set of primarily multispecific sera with a panel of random donors has, up to now, formed the main basis for the definition of antigenic specificities on human leukocytes (van Rood, 1962; Payne et al. 1964; see also Histocompatibility Testing, 1965). The reason for this approach is that the technical problems of large-scale absorption of multispecific sera hinder the simple definition of antigenic specificities by more conventional immunological procedures. In this paper, the analysis of the population associations between the antigenic specificities (as opposed to the associations between individual sera), which has formed the basis for the preliminary definition of the relationships between the genes controlling these specificities, will be discussed (Payne et al. 1964; Bodmer and Payne 1965). A family that clearly demonstrates the independence of the LA and 4 systems will be described. A new antigen, LA3, of the LA system will also be described. Predictions of the prevailing allelic combinations to be found in Caucasian populations will be made by application of the analysis of associations to the LA and 4 systems, using our own data and that of others.

Distribution and Quantity of Leukocyte Antigens in the Formed Elements of the Blood

The capacity of platelets, lymphocytes, leukocytes (mixed lymphocytes and granulocytes) and erythrocytes to absorb 12 leukocyte agglutinins from multiparous women was investigated. Erythrocytes did not absorb these agglutinins. Platelets, lymphocytes and granulocytes appeared to share antigens identified by representative antisera belonging to the Group 4 and the LA antigen systems. Leukocyte antisera specific for a single blood cell line were not encountered. Approximately 20 times as many platelets as lymphocytes or leukocytes were required to absorb an aliquot of serum. The quantities necessary for absorption indicate that whole blood is an inefficient source of antigen for large scale production of monospecific from multi‐specific leukocyte antisera.

Recombination and DNA replication in Bacillus subtilis transformation

Abstract A culture of Bacillus subtilis cells grown for many generations in heavy ( 15 N 2 H) medium containing [2- 14 C]thymidine was transferred midway through the competence regimen to light ( 14 N 1 H) medium and transforming DNA was added after the cells had become competent in the light medium. (Competent cells cannot be prepared in heavy medium.) DNA extracted from the resulting transforned cells was analyzed on a CsCl density gradient. Donor and recombinant transforming activity were found predominantly in the hybrid region, while the bulk of the DNA was predominantly in the fully replicated, light, region. This confirms the marked retardation of DNA synthesis in competent relative to non-competent cells. Recentrifuging the fractions between hybrid and light regions showed that the recombinant DNA was entirely hybrid in density. A parallel experiment indicated that the lysis procedures used in this experiment preserved the structure of the replicating points. Thus, integration does not appear to occur preferentially at replication point regions, which are expected at intermediate densities. These data do not, however, distinguish whether new replication points are induced by recombination or whether extensive repair DNA synthesis occurs after integration.

Preparation and characterization of 15N2H3H-labeled DNA from Bacillus subtilis and Escherichia coli phage T2

Abstract Bacillus subtilis and T2 phage have been grown on a medium containing the following isotopically labeled compounds: 15 N 2 H 4 Cl, thymidine- 3 H, deuterated sugars, and deuterated amino acids. The growth rates, titers, and thymidine- 3 H uptake are reported. 15 N 2 H 3 H-DNA has been isolated from these two organisms. Some physical properties of these DNA samples are reported. Studies on genetic activity of the B. subtilis DNA do not reveal any change produced by the substitution of 15 N 2 H 3 H for 14 N 1 H.

The Analysis of Genetic Variation Using Migration Matrices

One of the main aims of the population geneticist is to try to account for observed variations in gene and genotype frequencies over both time and space. Most populations are distributed irregularly in any given geographic area. Population sizes are often small enough so that, when variation over a relatively small geographic area is considered, simple deterministic models to account for the observed genetic variation are unsatisfactory because they ignore fluctuations due to random genetic drift. Though population sizes may be small, it is, nevertheless, rare for any given population to be sufficiently isolated from all others so that migration can be neglected. Even quite low levels of migration between relatively isolated populations may have very significant effects in counteracting divergence between them due to random fluctuations. Models to account for genetic variation observed in restricted geographic areas must, therefore, take into account population subdivisions of the area being studied and rates of migration between these subdivisions.

Natural selection for modifiers of heterozygote fitness

Abstract The paper elaborates the theoretical analyses which formed the basis of Parsons & Bodmers (1961) suggested mechanism for the evolution of overdominance. In a random mating population a new advantageous gene occurs initially much more often in heterozygotes than in homozygotes. Calculations are given for this relative preponderance of heterozygotes over homozygotes during the initial progress of a new advantageous gene. Following an argument similar to that used by Fisher (1928) for the evolution of dominance, it seems likely that during this initial stage modifiers will be selected principally for their effect on the heterozygote and their selection may result in the evolution of overdominance. When, on the other hand, overdominance has been achieved and has given rise to a balanced polymorphism, there is no longer the same differential selection in favor of the heterozygote. The results are discussed in relation to the significance of linkage and interaction between loci for the evolution of linked overdominant gene complexes.