Journal of Molecular Evolution

Two types of reactivities of thiophosphates have been demonstrated: one being nucleophilic displacement by the P-S moiety of nucleoside phosphorothioates and the other, phosphorylation via P-S cleavage as the driving force. We have designed a system where both displacement on carbon and P-S cleavage are possible. Adenosine derivatives have been synthesized with 5′-deoxy-5′-chloro and 5′-O-tosyl substitutions as leaving groups utilizing the 3′-O-phosphorothioate as the biphilic center. The main products of cyclization were 5′-O-tosyl and 5′-chloroadenosine 2′:3′-cyclic phosphate. Formation of 3′:5′-S-phosphorothioate was slow even using an excellent leaving group. This is possibly due to hydrogen bonding between the 2′-OH and the neighboring P-O.− KOH hydrolysis of the cyclic phosphorothioate yielded 2′(3′) phosphorothioates in a 1:1 ratio. The 2′ and 3′ isomers were separated and used to study the relative rates of cyclization. The cyclization via P-S cleavage of 2′(3′)-O-phosphorothioates showed that the 2′ isomer was more reactive. This is the first report of superior reactivity of the 3′-OH of a ribonucleoside.

Oligomerization of 5′-TMP in water pools entrapped by dodecyl-ammonium chloride surfactant aggregates in benzene: hexane in the presence of dicyanodiimide at temperatures ranging from 21°–72° resulted in the formation of linear and cyclic oligonucleotides containing up to pentamers. Effects of temperature, time and surfactants have been examined. Rate constants for the formation of oligomers have been determined at five different temperatures. These data afforded values of ΔH‡ = 11.8 ± 1.9 Kcal mole−1, ΔS‡=−53α 6 e.u. and ΔG‡ = 27.4α 4.0 Kcal mole−1. Prebiotic significance of these results are discussed.

Over half a decade has passed since the quantitative REH theory of evolutionary divergence in nucleic acids and proteins was published. The principle tenant of this theory is that natural selection and stochastic processes interact, the main effect of the former being to restrict those codon sites which may fix mutations. At the time it was published the theory predicted a magnitude for the total number of fixed nucleotide replacements that was appreciably larger than estimates then current. 'In the last two years these predictions have been confirmed in those protein families for which the experimental data base is large: cytochromec, α-hemoglobin,β-hemoglobin, and myoglobin. It has come to our attention, chiefly through private correspondance, but also in one published review, that certain aspects of the REH theory have caused confusion among some users. This paper discusses these particular aspects in some detail, restates the theory in a manner which emphasizes its essential simplicity, analyzes the magnitude of possible sources of errors, and considers some important statistical matters not dealt with elsewhere. The calculational methodology is simplified by replacing tables and graphs by polynomial expressions, and deriving a more simple expression for calculating the number of codons which have been free to fix mutations during some part of the period of divergence of two species. A statistical bias in the estimation of the fixation intensity is corrected. It is hoped these changes will make the method more accessible to those without extensive computing facilities.

Cationic amino acids, arginine and lysine partition differentially from water into aqueous micellar sodium dodecanoate. Conversely, partitioning of serine, glycine, aspartic acid, glutamic acid, threonine, alanine, proline, valine, leucine, phenylalanine and isoleucine do not vary appreciably. Partitioning from neat hexane into dodecylammonium propionate trapped water in hexane is, however, dependent upon both electrostatic and hydrophobic interactions. These results imply that the interior of dodecylammonium propionate aggregates is negatively charged and is capable of hydrogen bonding in addition to providing a hydrophobic environment. The solubilities of amino acids in neat hexane substantiate the previously derived amino acid hydrophobicity scale. Relevance of partitioning in these systems to the postulated selective amino acid compartmentalization is discussed.

Sequences from nuclear mitochondrial pseudogenes (numts) that originated by transfer of genetic information from mitochondria to the nucleus offer a unique opportunity to compare different regimes of molecular evolution. Analyzing a 1621-nt-long numt of the rRNA specifying mitochondrial DNA residing on human chromosome 3 and its corresponding mitochondrial gene in 18 anthropoid primates, we were able to retrace about 40 MY of primate rDNA evolutionary history. The results illustrate strengths and weaknesses of mtDNA data sets in reconstructing and dating the phylogenetic history of primates. We were able to show the following. In contrast to numt-DNA, (1) the nucleotide composition of mtDNA changed dramatically in the different primate lineages. This is assumed to lead to significant misinterpretations of the mitochondrial evolutionary history. (2) Due to the nucleotide compositional plasticity of primate mtDNA, the phylogenetic reconstruction combining mitochondrial and nuclear sequences is unlikely to yield reliable information for either tree topologies or branch lengths. This is because a major part of the underlying sequence evolution model — the nucleotide composition — is undergoing dramatic change in different mitochondrial lineages. We propose that this problem is also expressed in the occasional unexpected long branches leading to the “common ancestor” of orthologous numt sequences of different primate taxa. (3) The heterogeneous and lineage-specific evolution of mitochondrial sequences in primates renders molecular dating based on primate mtDNA problematic, whereas the numt sequences provide a much more reliable base for dating.