The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.     

Sequence variation at the major histocompatibility complex locus DQ beta in beluga whales (Delphinapterus leucas) [published erratum appears in Mol Biol Evol 1995 Nov;12(6):1174]

Genetic variation at the Major Histocompatibility Complex locus DQ beta was analyzed in 233 beluga whales (Delphinapterus leucas) from seven populations: St. Lawrence Estuary, eastern Beaufort Sea, eastern Chukchi Sea, western Hudson Bay, eastern Hudson Bay, southeastern Baffin Island, and High Arctic and in 12 narwhals (Monodon monoceros) sympatric with the High Arctic beluga population. Variation was assessed by amplification of the exon coding for the peptide binding region via the polymerase chain reaction, followed by either cloning and DNA sequencing or single-stranded conformation polymorphism analysis. Five alleles were found across the beluga populations and one in the narwhal. Pairwise comparisons of these alleles showed a 5:1 ratio of nonsynonymous to synonymous substitutions per site leading to eight amino acid differences, five of which were nonconservative substitutions, centered around positions previously shown to be important for peptide binding. Although the amount of allelic variation is low when compared with terrestrial mammals, the nature of the substitutions in the peptide binding sites indicates an important role for the DQ beta locus in the cellular immune response of beluga whales. Comparisons of allele frequencies among populations show the High Arctic population to be different (P < or = .005) from the other beluga populations surveyed. In these other populations an allele, Dele-DQ beta*0101-2, was found in 98% of the animals, while in the High Arctic it was found in only 52% of the animals. Two other alleles were found at high frequencies in the High Arctic population, one being very similar to the single allele found in narwhal.      

Significance of nucleotide sequence alignments: a method for random sequence permutation that preserves dinucleotide and codon usage

The similarity of two nucleotide sequences is often expressed in terms of evolutionary distance, a measure of the amount of change needed to transform one sequence into the other. Given two sequences with a small distance between them, can their similarity be explained by their base composition alone? The nucleotide order of these sequences contributes to their similarity if the distance is much smaller than their average permutation distance, which is obtained by calculating the distances for many random permutations of these sequences. To determine whether their similarity can be explained by their dinucleotide and codon usage, random sequences must be chosen from the set of permuted sequences that preserve dinucleotide and codon usage. The problem of choosing random dinucleotide and codon-preserving permutations can be expressed in the language of graph theory as the problem of generating random Eulerian walks on a directed multigraph. An efficient algorithm for generating such walks is described. This algorithm can be used to choose random sequence permutations that preserve (1) dinucleotide usage, (2) dinucleotide and trinucleotide usage, or (3) dinucleotide and codon usage. For example, the similarity of two 60-nucleotide DNA segments from the human beta-1 interferon gene (nucleotides 196-255 and 499-558) is not just the result of their nonrandom dinucleotide and codon usage.      

Galápagos and Californian sea lions are separate species: Genetic analysis of the genus Zalophus and its implications for conservation management

The climatic cycles with subsequent glacial and intergalcial periods have had a great impact on the distribution and evolution of species. Using genetic analytical tools considerably increased our understanding of these processes. In this review I therefore give an overview of the molecular biogeography of Europe. For means of simplification, I distinguish between three major biogeographical entities: (i) "Mediterranean" with Mediterranean differentiation and dispersal centres, (ii) "Continental" with extra-Mediterranean centres and (iii) "Alpine" and/or "Arctic" with recent alpine and/or arctic distribution patterns. These different molecular biogeographical patterns are presented using actual examples. Many "Mediterranean" species are differentiated into three major European genetic lineages, which are due to glacial isolation in the three major Mediterranean peninsulas. Postglacial expansion in this group of species is mostly influenced by the barriers of the Pyrenees and the Alps with four resulting main patterns of postglacial range expansions. However, some cases are known with less than one genetic lineage per Mediterranean peninsula on the one hand, and others with a considerable genetic substructure within each of the Mediterranean peninsulas, Asia Minor and the Maghreb. These structures within the Mediterranean sub-centres are often rather strong and in several cases even predate the Pleistocene. For the "Continental" species, it could be shown that the formerly supposed postglacial spread from eastern Palearctic expansion centres is mostly not applicable. Quite the contrary, most of these species apparently had extra-Mediterranean centres of survival in Europe with special importance of the perialpine regions, the Carpathian Basin and parts of the Balkan Peninsula. In the group of "Alpine" and/or "Arctic" species, several molecular biogeographical patterns have been found, which support and improve the postulates based on distribution patterns and pollen records. Thus, genetic studies support the strong linkage between southwestern Alps and Pyrenees, northeastern Alps and Carpathians as well as southeastern Alps and the Dinaric mountain systems, hereby allowing conclusions on the glacial distribution patterns of these species. Furthermore, genetic analyses of arctic-alpine disjunct species support their broad distribution in the periglacial areas at least during the last glacial period. The detailed understanding of the different phylogeographical structures is essential for the management of the different evolutionary significant units of species and the conservation of their entire genetic diversity. Furthermore, the distribution of genetic diversity due to biogeographical reasons helps understanding the differing regional vulnerabilities of extant populations.