Mosaic evolution of prepropancreatic polypeptide. II. Structural conservation and divergence in pancreatic polypeptide gene

We demonstrated that nucleotide and amino acid sequences in the carboxyl-terminal regions of rat, mouse, and human prepropancreatic polypeptide exhibit a high degree of divergence, whereas the amino-terminal domains are highly conserved. To understand the molecular basis of this divergence and conservation, we determined the nucleotide sequence of the rat pancreatic polypeptide gene from an islet genomic library and compared it with that of the human gene. Exon 2 of the rat gene encodes the signal peptide and pancreatic polypeptide, exon 3 encodes the carboxyl-terminal region, and exons 1 and 4 encode the 5'- and 3'- untranslated regions of the mRNA, respectively. Exons 1 and 2 of rat and human genes are well conserved. The rat and human genes, however, have exons 3 and 4 of different lengths and heterologous nucleotide sequences. Mutational accumulation in exons 3 and 4 and intron 3 of the rat gene appears to have caused splice junction sliding and translational frameshift, resulting in a structural divergence in the carboxyl-terminal region. Available evidence indicates that the mosaicism of structural conservation and divergence in pancreatic polypeptide genes may have been caused by a difference in the evolutionary rates of the genomic regions.     

A semi-quantitative, synteny-based method to improve functional predictions for hypothetical and poorly annotated bacterial and archaeal genes

During microbial evolution, genome rearrangement increases with increasing sequence divergence. If the relationship between synteny and sequence divergence can be modeled, gene clusters in genomes of distantly related organisms exhibiting anomalous synteny can be identified and used to infer functional conservation. We applied the phylogenetic pairwise comparison method to establish and model a strong correlation between synteny and sequence divergence in all 634 available Archaeal and Bacterial genomes from the NCBI database and four newly assembled genomes of uncultivated Archaea from an acid mine drainage (AMD) community. In parallel, we established and modeled the trend between synteny and functional relatedness in the 118 genomes available in the STRING database. By combining these models, we developed a gene functional annotation method that weights evolutionary distance to estimate the probability of functional associations of syntenous proteins between genome pairs. The method was applied to the hypothetical proteins and poorly annotated genes in newly assembled acid mine drainage Archaeal genomes to add or improve gene annotations. This is the first method to assign possible functions to poorly annotated genes through quantification of the probability of gene functional relationships based on synteny at a significant evolutionary distance, and has the potential for broad application.     

Learning Retention Mechanisms and Evolutionary Parameters of Duplicate Genes from Their Expression Data

Learning about the roles that duplicate genes play in the origins of novel phenotypes requires an understanding of how their functions evolve. A previous method for achieving this goal, CDROM, employs gene expression distances as proxies for functional divergence and then classifies the evolutionary mechanisms retaining duplicate genes from comparisons of these distances in a decision tree framework. However, CDROM does not account for stochastic shifts in gene expression or leverage advances in contemporary statistical learning for performing classification, nor is it capable of predicting the parameters driving duplicate gene evolution. Thus, here we develop CLOUD, a multi-layer neural network built on a model of gene expression evolution that can both classify duplicate gene retention mechanisms and predict their underlying evolutionary parameters. We show that not only is the CLOUD classifier substantially more powerful and accurate than CDROM, but that it also yields accurate parameter predictions, enabling a better understanding of the specific forces driving the evolution and long-term retention of duplicate genes. Further, application of the CLOUD classifier and predictor to empirical data from Drosophila recapitulates many previous findings about gene duplication in this lineage, showing that new functions often emerge rapidly and asymmetrically in younger duplicate gene copies, and that functional divergence is driven by strong natural selection. Hence, CLOUD represents a major advancement in classifying retention mechanisms and predicting evolutionary parameters of duplicate genes, thereby highlighting the utility of incorporating sophisticated statistical learning techniques to address long-standing questions about evolution after gene duplication.     

A molecular description of telometic heterochromatin in secale species

We report the nucleotide sequence of a rabbit β-globin pseudogene, ψβ2. A comparison of the ψβ2 sequence with that of the rabbit adult β-globin gene, β1, reveals the presence of frameshift mutations and premature termination codons in the protein coding sequence which render ψβ2 unable to encode a functional β-globin polypeptide. ψβ2 contains two intervening sequences at the same locations in the globin protein coding sequence as β1 and all other sequenced β-globin genes. An examination of the DNA sequences at the intron/exon junctions suggests that a putative ψβ2 precursor mRNA could not be spliced normally. We compare the flanking and noncoding sequences of ψβ2 and β1 and discuss the evolutionary relationship between these two genes.     

Codon usage in histone gene families of higher eukaryotes reflects functional rather than phylogenetic relationships

Summary The nucleic acid sequences coding for 23 H3 histone genes from a variety of species have been analyzed using a computer assisted alignment and analysis program. Although these histones are highly conserved within and between highly divergent species, they represent various classes of histones whose patterns of expression are distinctively regulated. Surprisingly, in dendrograms derived from these comparisons, H3 sequences cluster according to their modes of regulation rather than phylogenetically. These clusters are generated from highly distinctive patterns of codon usage within the functional gene classes. We suggest that one factor involved in specifying the differing codon usage patterns between functional classes is a difference in requirements for rapid translation of mRNA. In addition, the data presented here, together with structural and sequence information, suggest a heterodox evolutionary model in which genes related to the intron-bearing, basally expressed H3.3 vertebrate genes are the ancestors of the intronless H3. 1 class of genes of higher eukaryotes. The H3. 1 class must have arisen, therefore, following duplication of a primitive H3.3 gene, but prior to the plant-animal divergence. Implications of the data presented are discussed with regard to functional and evolutionary relationships.     

MADS-box基因家族基因重复及其功能的多样性

基因的重复(duplication)及其功能的多样性(diversification)为生物体新的形态进化提供了原材料。MADS-box基因在植物(特别是被子植物)的进化过程中发生了大规模的基因重复事件而形成一个多基因家族。MADS-box基因家族的不同成员在植物生长发育过程中起着非常重要的作用,在调控开花时间、决定花分生组织和花器官特征以及调控根、叶、胚珠及果实的发育中起着广泛的作用。探讨MADS-box基因家族的进化历史有助于深入了解基因重复及随后其功能分化的过程和机制。本文综述了MADS-box基因家族基因重复及其功能分化式样的研究进展。     

MADS-box 基因家族基因重复及其功能的多样性

基因的重复(duplication)及其功能的多样性(diversification)为生物体新的形态进化提供了原材料。MADS-box基因在植物(特别是被子植物)的进化过程中发生了大规模的基因重复事件而形成一个多基因家族。MADS-box基因家族的不同成员在植物生长发育过程中起着非常重要的作用, 在调控开花时间、决定花分生组织和花器官特征以及调控根、叶、胚珠及果实的发育中起着广泛的作用。探讨MADS-box基因家族的进化历史有助于深入了解基因重复及随后其功能分化的过程和机制。本文综述了MADS-box基因家族基因重复及其功能分化式样的研究进展。     

Frequent appearance of novel protein-coding sequences by frameshift translation

Genomic duplication, followed by divergence, contributes to organismal evolution. Several mechanisms, such as exon shuffling and alternative splicing, are responsible for novel gene functions, but they generate homologous domains and do not usually lead to drastic innovation. Major novelties can potentially be introduced by frameshift mutations and this idea can explain the creation of novel proteins. Here, we employ a strategy using simulated protein sequences and identify 470 human and 108 mouse frameshift events that originate new gene segments. No obvious interspecies overlap was observed, suggesting high rates of acquisition of evolutionary events. This inference is supported by a deficiency of TpA dinucleotides in the protein-coding sequences, which decreases the occurrence of translational termination, even on the complementary strand. Increased usage of the TGA codon as the termination signal in newer genes also supports our inference. This suggests that tolerated frameshift changes are a prevalent mechanism for the rapid emergence of new genes and that protein-coding sequences can be derived from existing or ancestral exons rather than from events that result in noncoding sequences becoming exons.