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Molecular evolution of evolutionary novelties: the vagina and uterus of therian mammals.

Innovations are an integral part of the evolutionary process if we accept the fact that more complex organisms derived from anatomically simple ones. All major taxa are distinguished not only by their closer genealogical relatedness relative to other species but also by the possession of novel anatomical and physiological features. The question is whether the origin of these novel characters can be simply understood as adaptations, like all other phenotypic differences that arise by natural selection, or whether the origin of these characters requires more profound genetic changes. In this paper, we argue that innovations constitute a distinct class of evolutionary processes that require a research program complementary to the study of adaptation. The distinguishing feature of innovations is the origin of novel organ identity gene functions specific to the novel character. By implication, research into the origin of novel characters has to identify the developmental regulatory links that were involved in the evolution of these characters. We suggest that novel regulatory links will include the evolution of cis-regulatory elements as well as novel protein-protein interactions among transcription factor proteins. The latter hypothesis suggests that innovations should leave a trace in the evolution of the protein coding regions of transcription factor genes. We illustrate this idea with results on the evolution of HoxA-11 and HoxA-13 in the stem lineage of placental mammals. These genes are essential for female reproductive tract development and function. We show that, as predicted, these genes experience strong directional selection in the stem lineage of placental mammals and that these amino acid substitutions affect residues at the surface of the protein, consistent with their expected role in protein-protein interactions. We conclude that a careful analysis of sequence variation in developmental genes can aid in testing which developmental changes were instrumental in the origin of novel morphological characters.

Animals↗

Pharmacological activities in thermal proteins: relationships in molecular evolution.

The model of protobiological events that has been presented in these pages has increasing relevance to pharmacological research. The thermal proteins that function as key substances in the proteinoid theory have recently been found to prolong the survival of rat forebrain neurons in culture and to stimulate the growth of neurites. A search for such activity in thermal proteins added to cultures of modern neurons was suggested by the fact that some of the microspheres assembled from proteinoids rich in hydrophobic amino acids themselves generate fibrous outgrowths.

Amino Acids↗

Molecular evolution and structure--function relationships of the superoxide dismutase gene families in angiosperms and their relationship to other eukaryotic and prokaryotic superoxide dismutases.

This study assesses whether the phylogenetic relationships between SODs from different organisms could assist in elucidating the functional relationships among these enzymes from evolutionarily distinct species. Phylogenetic trees and intron positions were compared to determine the relationships among these enzymes. Alignment of Cu/ZnSOD amino acid sequences indicates high homology among plant sequences, with some features that distinguish chloroplastic from cytosolic Cu/ZnSODs. Among eukaryotes, the plant SODs group together. Alignment of the Mn and FeSOD amino acid sequences indicates a higher degree of homology within the group of MnSODs (>70%) than within FeSODs (approximately 60%). Tree topologies are similar and reflect the taxonomic classification of the corresponding species. Intron number and position in the Cu/Zn Sod genes are highly conserved in plants. Genes encoding cytosolic SODs have seven introns and genes encoding chloroplastic SODs have eight introns, except the chloroplastic maize Sod1, which has seven. In Mn Sod genes the number and position of introns are highly conserved among plant species, but not among nonplant species. The link between the phylogenetic relationships and SOD functions remains unclear. Our findings suggest that the 5' region of these genes played a pivotal role in the evolution of function of these enzymes. Nevertheless, the system of SODs is highly structured and it is critical to understand the physiological differences between the SODs in response to different stresses in order to compare their functions and evolutionary history.

Amino Acid Sequence↗

Molecular evolution of myelin proteolipid protein.

We show that the major membrane protein of central nervous system myelin, proteolipid protein, evolved much more rapidly than it does now more than 300 million years ago. We reason that myelin proteolipid protein evolved rapidly just after its appearance in vertebrates and that its evolutionary rate then gradually decreased. Comparison of the rates between the synonymous and nonsynonymous nucleotide substitutions for the cDNA suggests the possibility that positive selection operated on myelin proteolipid protein at least when it appeared in vertebrates.

Amino Acid Sequence↗

Darwinian aspects of molecular evolution at sublinear propagation rates.

Mean fitness is non-decreasing in the symmetry sector of the frequency trajectory followed in competitive replication at sublinear propagation rates (parabolic time course). This sector contains the pairwise symmetric distribution of species frequencies and its neighboring states, and represents at least half the possible states of an evolving sublinear system. States is the non-symmetry sector produce a negative rate of change in mean fitness. The heterogeneous steady state attained in a finite sublinear system is destabilized by formation of a variant with above-threshold fitness. Evolution in the post-steady-state interval elevates the fitness threshold for coexistence. Contrary to the proposition that 'parabolic growth invariably results in the survival of all competing species', only species with sufficient fitness to avoid subthreshold fitness survive.

Evolution, Molecular↗

Molecular evolution of fish neurohypophysial hormones: neutral and selective evolutionary mechanisms.

Chemical identification of neurohypophysial hormones from about 80 vertebrate species reveals that two evolutionary lineages can be traced in bony vertebrates, a vasopressin-like hormone line and an oxytocin-like hormone line, which were derived from the duplication of an ancestral gene that may have been present in agnathans. All of the 13 neurohypophysial hormones are built in the same structural pattern, namely, a nonapeptide with a disulfide bridge linking half-cystines in positions 1 and 6. There is a striking evolutionary stability in bony vertebrates since virtually all species belonging to a given class are endowed with the same peptides. In contrast, in cartilaginous fishes, the oxytocin-like hormone displays a great diversity. Six distinct peptides are characterized in this group. The proposed hypothesis is that the stability in primary structure in bony vertebrates is due to selective pressure. This selective pressure is associated with an ion-based osmoregulation, whereas in Chondrichthyes the occurrence of an urea-based osmoregulation has relieved the hormones from the control of ionic homeostasis. Variations in primary structures in cartilaginous fishes are regarded as relevant to the neutral evolution as defined by Kimura. According to this concept, oxytocin of placental mammals results from selective evolution, whereas the same molecule found in ratfish proceeds from random genetic drift.

Animals↗

Molecular evolution of the opioid/orphanin gene family.

Gene duplication is a recurring theme in the evolution of vertebrate polypeptide hormones and neuropeptides. These duplication events can lead to the formation of gene families in which divergence of function is the usual outcome. In the case of the opioid/orphanin family of genes, duplication events have proceeded along two paths: (a) an apparent duplication of function as seen in the analgesic activity of Proenkephalin and Prodynorphin end-products; and (b) divergence of function as seen in the nociceptic activity of Proorphanin end-products or the melanocortin (color change and chronic stress regulation) activity of Proopiomelanocortin end-products. Although genes coding for Proopiomelanocortin, Proenkephalin, Prodynorphin, and Proorphanin have been extensively studied in mammals, the distribution and radiation of these genes in nonmammalian vertebrates is less well understood. This review will present the hypothesis that the radiation of the opioid/orphanin gene family is the result of the duplication and divergence of the Proenkephalin gene during the radiation of the chordates. To evaluate the Proenkephalin gene duplication hypothesis, a 3'RACE procedure was used to screen for the presence of Prodynorphin-related, Proenkephalin-related, and Proorphanin-related cDNAs expressed in the brains of nonmammalian vertebrates.

Amino Acid Sequence↗

Molecular evolution of leptin.

Leptin, a hormone produced mainly by adipocytes, is involved in the regulation of food intake, metabolism, and reproduction. The objective of this study was to determine the evolutionary relationships of leptin genes. Partial nucleotide sequences of leptin were cloned and sequenced from six mammalian species: large hairy armadillo (Chaetophractus villosus), rabbit (Oryctolagus cuniculus), big brown bat (Eptesicus fuscus) [corrected], striped skunk (Mephitis mephitis), raccoon (Procyon lotor), and beluga whale (Delphinapterus leucas). The PUZZLE program was used to construct maximum-likelihood trees. Our phylogenetic analysis shows that the grouping of these new mammalian sequences with those currently available in GenBank respect the evolutionary relationships generally accepted for mammals. However, when leptin sequences for chicken and turkey are included in the analysis, these are found to group with mouse and rat leptins. Chicken and mouse leptins are 95% identical. However, when mouse is compared with closer relatives, such as rabbit or bat, identities are approximately 80%. A comparison of extant and ancestral leptin sequences suggests that convergent or parallel evolution is the most plausible hypothesis to explain the similarity between bird and rodent leptins.

Adipose Tissue↗

Molecular evolution of the C-terminal cytoplasmic domain of a superfamily of bacterial receptors involved in taxis.

Twenty-nine proteins from 16 different species of prokaryotes revealed an extensive sequence homology with the cytoplasmic domain of the Escherichia coli aspartate receptor. The high percentage of identity indicated that they constitute a superfamily of proteins. A consensus secondary structure consisting mostly of alpha-helices was predicted. The occurrence of a seven-residue repeat (a-b-c-d-e-f-g), in which both the a and d residues were hydrophobic with few exceptions, provided additional evidence for a conserved alpha-helical conformation. Sequence alignments, together with the predicted secondary structure, led to identification of the boundaries for the functional units constituting the cytoplasmic domain. Putative methylation sites were assigned for all the members of this superfamily. These proteins could be grouped into three classes based on the presence of 14-residue insertion/deletion regions found within both the signalling and the methylation functional units of the cytoplasmic domain. The gene coding for the C-terminal cytoplasmic domain of these proteins apparently evolved through gene duplication from a common ancestor in which the four original 14-residue insertion/deletion regions were deleted two by two during evolution.

Amino Acid Sequence↗

Molecular evolution near a two-locus balanced polymorphism.

Balancing selection at one locus can increase the amount of selectively neutral variation within neighboring genomic regions. Discrete phenotypic polymorphisms studied in natural populations are frequently determined by sets of interacting genes instead of alternative alleles at single loci. We extend coalescent theory to investigate balancing selection on combinations of linked genes. We find that variation at neutral sites is increased across a much larger genomic region relative to the single-locus models: the entire region lying between the two loci in balanced combination is affected to some degree. Epistatic selection maintains these high levels of neutral variation because it directly opposes the homogenizing effect of recombination. The results of the theory are discussed in relation to published gene sequence data, primarily from Drosophila.

Alleles↗

Molecular evolution of catalysis.

In this paper, we consider the evolutionary dynamics of catalytically active species with a distinct genotype-phenotype relationship. Folding landscapes of RNA molecules serve as a paradigm for this relationship with essential neutral properties. The landscape itself is partitioned by phenotypes (realized as RNA secondary structures). To each genotype (represented as a sequence) a structure is assigned in a unique way. The set of all sequences which map into a particular structure is modeled as a random graph in sequence space (the so-called neutral network). A catalytic network is realized as a random digraph with maximal out-degree two and secondary structures as vertex sets. A population of catalytic RNA molecules shows significantly different behavior compared to a deterministic description: hypercycles are able to co-exist and out-compete a parasite with superior catalytic support. A "switching" between different dynamic organizations of the network can be observed, dynamical stability of hypercyclic organizations against errors and the existence of an error-threshold of catalysis can be reported.

Animals↗

Molecular evolution of the cottoid fish endemic to Lake Baikal deduced from nuclear DNA evidence.

Lake Baikal in Eastern Siberia contains a remarkable flock of 29 species of teleost fishes of the suborder Cottoidei (sculpins, bullheads) that are endemic to the lake and its associated rivers and occupy all depth habitats down to over 1500 m. The species are divided into three families, the Cottidae with 7 species, the Abyssocottidae with 20 species, and the Comephoridae with 2 species. Nucleotide sequences of the rod opsin gene from 12 of these species, plus a non-Baikal marine species, have been used to examine the evolutionary relations and the divergence time of the flock. Phylogenetic trees, generated by neighbor-joining and maximum parsimony, indicate that the unique Comephoridae family with its viviparity and unusual appearance is closely related to the Cottidae and Abyssocottidae, whereas the genus Cottocomephorus, at present placed in the Cottidae, was the first to diverge from the ancestral species and forms a separate lineage. The major adaptation to deep water would appear to be of relatively recent origin, and there is evidence that the ancestral species occupied a shallow-water-marine or brackish habitat. Estimates of antiquity obtained from synonymous substitutions place the origin of the species flock at around 4.9 million years ago.

Animals↗

Molecular evolution and phylogenetic utility of the chloroplast rpl16 intron in Chusquea and the Bambusoideae (Poaceae).

Phylogenetic relationships within Chusquea, a diverse genus of neotropical woody bamboos, and among selected members of the Bambusoideae were explored using rpl16 intron sequence data from the chloroplast genome. Mechanisms of mutation, including slipped-strand mispairing, secondary structure, minute inversions, and base substitutions, were examined within the rpl16 intron, and their effects on sequence alignment and phylogenetic analysis were investigated. Thirty-five bamboo sequences were generated and two separate matrices were analyzed using maximum parsimony. In the first, 23 sequences from Chusquea, 1 of Neurolepis, and 3 outgroups were included. Neurolepis was supported as sister to Chusquea, Chusquea was strongly supported as a monophyletic lineage, and three species of Chusquea subg. Rettbergia were resolved as the most basal clade within the genus. In the second analysis, 15 sequences, 14 from across the subfamily and 1 outgroup, were included. A Bambusoideae clade was recovered with the Olyreae/Parianeae (herbaceous bamboos) and the Bambuseae (woody bamboos) each supported as monophyletic. Two clades corresponding to temperate and tropical woody bamboos were derived within the Bambuseae and the tropical taxa were further split into New World and Old World clades. The rpl16 intron in bamboos was found to be susceptible to frequent length mutations of multiple origins, nonindependent character evolution, and regions of high mutability, all of which created difficulties in alignment and phylogenetic analysis; nonetheless the rpl16 intron is phylogenetically informative at the inter- and intrageneric levels in bamboos.

Chloroplasts↗

Molecular evolution of the internal transcribed spacers (ITS1 and ITS2) and phylogenetic relationships among species of the family Cucurbitaceae.

Phylogenetic relationships of different members of the family Cucurbitaceae were estimated from sequences of the internal transcribed spacer (ITS1 and ITS2) regions of the nuclear ribosomal RNA genes. Twenty-six species of different genera belonging to different tribes and several subtribes were analyzed. The whole ITS regions were amplified by PCR technique and cloned, and three to five different clones of each species were sequenced; for some species PCR products were sequenced directly. ITS1 and ITS2 regions are slightly variable in length, with each length appearing genus-specific. A substitution rate of 3.62 x 10(-9) substitutions per site per year was calculated assuming 40 MYA separation time. Phylogenetic relationships inferred from ITS sequences of some species is in agreement with morphological data, but deviations to the taxonomic classification were also observed. A polyphyletic origin of the New World species must be considered. In the genus Cucurbita different "types" of ITS sequences within one species exist, possibly due to the high frequency of introgression during domestication or due to polyploidization events; in contrast, low intraspecific variability was detectable in the genus Cucumis, indicating different stages of speciation.

Base Composition↗

Comparing molecular evolution in two mitochondrial protein coding genes (cytochrome b and ND2) in the dabbling ducks (Tribe: Anatini).

Rates of sequence evolution were estimated for the cytochrome b (cyt b) and NADH dehydrogenase sub-unit 2 (ND2) genes using a phylogeny of the dabbling ducks (Tribe: Anatini) and outgroups. This speciose group was densely sampled, reducing the impact of undetected homoplasy on rate comparisons. Phylogenies based on sequences of the two gene regions and various weighting schemes differed, but most of the differences involved weakly supported nodes. In addition, partition homogeneity tests show that these differences were not due to statistically significant conflict between the data sets. Cyt b and ND2 also showed similar rates and types of both nucleotide and amino acid substitutions. For both genes, substitutions between isoleucine and valine and between alanine and threonine were most common; both of these substitution types are the result of A-G transitions at first positions of codons. Rates of sequence evolution varied substantially and significantly among nucleotide positions, and even within a given codon position (first, second, or third), rates were significantly heterogeneous among sites. Within Anatini, cyt b and ND2 show similar levels of variation and homoplasy, and are equally useful for reconstructing the species level phylogeny of this group.

Amino Acid Substitution↗

Molecular evolution of type 1 serine/threonine protein phosphatases.

Type 1 serine/threonine protein phosphatases (PP1s) play key roles in many cellular processes. To understand the evolutionary relationships among PP1s from various kingdoms and to provide a valid basis to evaluate the structure-function relationships of these phosphatases, 44 PP1 sequences were aligned, revealing a high sequence similarity among PP1 homologs. About one-third of the total amino acids are conserved in all the sequences studied. Most of these conserved amino acids are located within a 270-amino-acid core region. They include most sites critical to the activity and regulation of PP1s based on three-dimensional structural studies of mammalian PP1s. Positional variation analysis using a sliding window approach revealed two variable blocks in the 270-amino-acid core region. The major variable block corresponds to a subdomain composed of three alpha-helices (alphaG, alphaH, and alphaI) and three beta-sheets (beta7, beta8, and beta9). Phylogenetic analyses suggested that plant and animal PP1s form distinct monophyletic groups. The plant PP1 family contains several subgroups that may be older than the monocot-dicot divergence. In the animal PP1 family, different vertebrate isoforms appear to form distinct subgroups. Relative substitution rate studies indicated that plant PP1s are more diverse than animal PP1s, with an average substitution rate 1.5 times as large as that of animal PP1s. The possible involvement of PP1s in the establishment of multicellularity is discussed.

Amino Acid Sequence↗

Molecular evolution and phylogeny of the Drosophila saltans species group inferred from the Xdh gene.

The Drosophila saltans group of the subgenus Sophophora consists of five species subgroups whose phylogenetic relationships are poorly known. We have analyzed 2085 coding nucleotides from the xanthine dehydrogenase (Xdh) gene in six species, at least one from each subgroup. We follow a model-based maximum likelihood framework. We first model the substitution process using a tree topology that is approximately accurate. Then we evaluate several candidate tree topologies using a working model of nucleotide substitution. We found that a minimally realistic description of the substitution process along the Xdh region should allow two transition and four transversion rate parameters and different fixed rates for codon positions, which are distributed statistically according to different gamma distributions. The phylogeny obtained using this description differs in significant respects from a phylogeny based on anatomical criteria. We have also analyzed data from five additional (three nuclear and two mitochondrial) gene regions. In our analysis, these relatively short DNA sequences, either separately or jointly, fail to discriminate statistically among alternative phylogenies. When the data for these five gene regions are combined with the Xdh sequences, the strong phylogenetic signal emerging from Xdh becomes somewhat diluted rather than reinforced. The phylogeny of the species and biogeographical considerations suggest that the D. saltans group originated in the tropics of the New World, similarly as the closely related D. willistoni group.

Alcohol Dehydrogenase↗