The main problem of studying biological evolution

The evolutionary aspect of the emergence problem is the main problem of studying the laws of biological evolution. A possible mechanism of how an ontogenetically modified phenotype (phenotypic modification, “morphosis”) is fixed in the genotype – the problem of “genetic assimilation” is considered. In particular, it is assumed that adaptive mutagenesis is involved in this, generating random multiple mutations that are “not Lamarckian”, but Darwinian, because they occur in random places in the genome. Stress-induced mutations that arise as a result of error-prone repair processes, while not targeting specific genes, are not randomly scattered around the genome. On the contrary, these mutations are concentrated around double-stranded DNA breaks caused by various stressors. It is assumed that the breaks occur with greater probability in actively transcribed DNA regions, reflecting the current activity of the organism and being the most open DNA regions. All this creates the conditions for the more likely appearance of useful mutations in the “trained” locus of the genome. Keywords: selectogenesis, nomogenesis, genetic assimilation, stress-mutagenesis.

MsDpo4—a DinB Homolog fromMycobacterium smegmatis—Is an Error-Prone DNA Polymerase That Can Promote G:T and T:G Mismatches

Error-prone DNA synthesis in prokaryotes imparts plasticity to the genome to allow for evolution in unfavorable environmental conditions, and this phenomenon is termed adaptive mutagenesis. At a molecular level, adaptive mutagenesis is mediated by upregulating the expression of specialized error-prone DNA polymerases that generally belong to the Y-family, such as the polypeptide product of thedinBgene in case ofE. coli. However, unlikeE. coli, it has been seen that expression of the homologs ofdinBinMycobacterium tuberculosisare not upregulated under conditions of stress. These studies suggest that DinB homologs inMycobacteriamight not be able to promote mismatches and participate in adaptive mutagenesis. We show that a representative homolog fromMycobacterium smegmatis(MsDpo4) can carry out template-dependent nucleotide incorporation and therefore is a DNA polymerase. In addition, it is seen that MsDpo4 is also capable of misincorporation with a significant ability to promote G:T and T:G mismatches. The frequency of misincorporation for these two mismatches is similar to that exhibited by archaeal and prokaryotic homologs. Overall, our data show that MsDpo4 has the capacity to facilitate transition mutations and can potentially impart plasticity to the genome.

ADAPTIVE MUTAGENESIS IN THE YEAST SACCHAROMYCES CEREVISIAE

The nature of mutation in microorganisms has been debated for a long time. Two theories have been at odds: random spontaneous mutagenesis vs. adaptive mutagenesis. "random mutagenesis" means that mutations occur in proliferating cells before they encountered the selective agent. "adaptive mutagenesis" means that advantageous mutations form in the environment where they have been selected, in non-replicating or poorly replicating cells even though other, non-selected, mutations occur at the same time. In the last 20 years it has been definitely shown that random as well as adaptive mutagenesis occur in bacteria and yeast. microorganisms in nature do not divide or divide poorly because of adverse environmental conditions; therefore adaptive mutations could provide cells with a selective advantage and allow evolution of populations. Here we will focus on some fundamental aspects of adaptive mutagenesis in the yeast Saccharomyces cerevisiae. We begin with a historical overview on the nature of mutation. We then focus on experimental systems aimed at proving or disproving adaptive mutagenesis. We have briefly summarized the results obtained in this field, with particular attention to genetic and molecular mechanisms.

Novel Role of mfd: Effects on Stationary-Phase Mutagenesis in Bacillus subtilis

ABSTRACT Previously, using a chromosomal reversion assay system, we established that an adaptive mutagenic process occurs in nongrowing Bacillus subtilis cells under stress, and we demonstrated that multiple mechanisms are involved in generating these mutations (41, 43). In an attempt to delineate how these mutations are generated, we began an investigation into whether or not transcription and transcription-associated proteins influence adaptive mutagenesis. In B. subtilis, the Mfd protein (transcription repair coupling factor) facilitates removal of RNA polymerase stalled at transcriptional blockages and recruitment of repair proteins to DNA lesions on the transcribed strand. Here we demonstrate that the loss of Mfd has a depressive effect on stationary-phase mutagenesis. An association between Mfd mutagenesis and aspects of transcription is discussed.