An Intron of Invertebrate Microphthalmia Transcription Factor Gene Is Evolved from a Longer Ancestral Sequence.

Introns are highly variable in number and size. Sequence simulation is an effective method to elucidate intron evolution patterns. Previously, we have reported that introns are more likely to evolve through mutation-and-deletion (MD) rather than through mutation-and-insertion (MI). In the present study, we further studied evolution models by allowing insertion in the MD model and by allowing deletion in the MI model at various frequencies. It was found that all deletion-biased models with proper parameter settings could generate sequences with attributes matchable to 16 invertebrate introns from the microphthalmia transcription factor gene, whereas all insertion-biased models with any parameter settings failed to generate such sequences. We conclude that the examined invertebrate introns may have evolved from a longer ancestral sequence in a deletion-biased pattern. The constructed models are useful for studying the evolution of introns from other genes and/or from other taxonomic groups. (C++ scripts of all deletion- and insertion-biased models are available upon request.).

Human SARS-CoV-2 has evolved to reduce CG dinucleotide in its open reading frames.

The outbreak of COVID-19 has brought great threat to human health. Its causative agent is a severe acute respiratory syndrome-related coronavirus which has been officially named SARS-CoV-2. Here we report the discovery of extremely low CG abundance in its open reading frames. We found that CG reduction in SARS-CoV-2 is achieved mainly through mutating C/G into A/T, and CG is the best target for mutation. Meanwhile, 5'-untranslated region of SARS-CoV-2 has high CG content and is capable of forming an internal ribosome entry site (IRES) to recruit host ribosome for translating its RNA. These features allow SARS-CoV-2 to reproduce efficiently in host cells, because less energy is consumed in disrupting the stem-loops formed by its genomic RNA. Notably, genomes of cellular organisms also have very low CG abundance, suggesting that mutating C/G into A/T occurs universally in all life forms. Moreover, CG is the dinucleotide related to CpG island, mutational hotspot and single nucleotide polymorphism in cellular organisms. The relationship between these features is worthy of further investigations.

Simulation of Chordate Intron Evolution Using Randomly Generated and Mutated Base Sequences.

Introns are well known for their high variation not only in length but also in base sequence. The evolution of intron sequences has aroused broad interest in the past decades. However, very little is known about the evolutionary pattern of introns due to the lack of efficient analytical method. In this study, we designed 2 evolutionary models, that is, mutation-and-deletion (MD) and mutation-and-insertion (MI), to simulate intron evolution using randomly generated and mutated bases by referencing to the phylogenetic tree constructed using 14 chordate introns from TF4 (transcription factor-like protein 4) gene. A comparison of attributes between model-generated sequences and chordate introns showed that the MD model with proper parameter settings could generate sequences that have attributes matchable to chordate introns, whereas the MI model with any parameter settings failed in doing so. These data suggest that the surveyed chordate introns have evolved from a long ancestral sequence through gradual reduction in length. The established methodology provides an effective measure to study the evolutionary pattern of intron sequences from organisms of various taxonomic groups. (C++ scripts of MD and MI models are available upon request.).