Molecular evolution of the genes encoding receptor tyrosine kinase with immunoglobulinlike domains

Receptor tyrosine kinases (RTK) with five, three, or seven immunoglobulinlike domains in their extracellular regions are classified as subclasses III, IV, and V, respectively. Conservation of the exon/intron structure of the downstream part of the human KIT, FMS, and FLT3 genes that encode RTK of subclass III together with the particular chromosomal localization of these genes suggests that RTKIII genes have evolved from a common ancestor by cis and trans duplications. To strengthen this model of evolution and to determine if it can be extended to RTKIV and V genes, we constructed a phylogenetic tree of RTKIII, IV, and V on the basis of a multiple alignment of their catalytic tyrosine kinase domain sequences and determined the exon/intron structure of PDGFRA (subclass III), FGFR4 (subclass IV), and FLT4 (subclass V) genes in their downstream part. Phylogenetic analyses with amino acid or nucleotide sequences both resulted in one most parsimonious tree. The phylogenetic trees obtained indicate that all three subclasses are well individuated and that RTKIII and RTKV are closer to each other than RTKIV. Furthermore, RTKIII and FLT4 (subclass V) genes possess the same exon/intron structure in their downstream part while the structure of the RTKIV genes is very similar to that of RTKIII and FLT4. Both approaches are in complete agreement and indicate that RTKIII, IV, and V genes most probably evolved from a common ancestor already in pieces by successive duplications involving entire genes.Correspondence to: F. Agnès     

The evolution of proteins from random amino acid sequences: II. Evidence from the statistical distributions of the lengths of modern protein sequences

This paper continues an examination of the hypothesis that modern proteins evolved from random heteropeptide sequences. In support of the hypothesis, White and Jacobs (1993, J Mol Evol 36:79–95) have shown that any sequence chosen randomly from a large collection of nonhomologous proteins has a 90% or better chance of having a lengthwise distribution of amino acids that is indistinguishable from the random expectation regardless of amino acid type. The goal of the present study was to investigate the possibility that the random-origin hypothesis could explain the lengths of modern protein sequences without invoking specific mechanisms such as gene duplication or exon splicing. The sets of sequences examined were taken from the 1989 PIR database and consisted of 1,792 super-family proteins selected to have little sequence identity, 623 E. coli sequences, and 398 human sequences. The length distributions of the proteins could be described with high significance by either of two closely related probability density functions: The gamma distribution with parameter 2 or the distribution for the sum of two exponential random independent variables. A simple theory for the distributions was developed which assumes that (1) protoprotein sequences had exponentially distributed random independent lengths, (2) the length dependence of protein stability determined which of these protoproteins could fold into compact primitive proteins and thereby attain the potential for biochemical activity, (3) the useful protein sequences were preserved by the primitive genome, and (4) the resulting distribution of sequence lengths is reflected by modern proteins. The theory successfully predicts the two observed distributions which can be distinguished by the functional form of the dependence of protein stability on length.The theory leads to three interesting conclusions. First, it predicts that a tetra-nucleotide was the signal for primitive translation termination. This prediction is entirely consistent with the observations of Brown et al. (1990a,b, Nucleic Acids Res 18:2079–2086 and 18: 6339-6345) which show that tetra-nucleotides (stop codon plus following nucleotide) are the actual signals for termination of translation in both prokaryotes and eukaryotes. Second, the strong dependence of statistical length distributions on sequence-termination signaling codes implies that the evolution of stop codons and translation-termination processes was as important as gene splicing in early evolution. Third, because the theory is based upon a simple no-exon stochastic model, it provides a plausible alternative to a limited universe of exons from which all proteins evolved by gene duplication and exon splicing (Dorit et al. 1990, Science 250:1377–1382).     

The success of sequence capture in relation to phylogenetic distance from a reference genome: a case study of avian haemosporidian parasites

Genomic sequencing of avian haemosporidian parasites (Haemosporida) has been challenging due to excessive contamination from host DNA. In this study, we developed a cost-effective protocol to obtain parasite sequences from naturally infected birds, based on targeted sequence capture and next generation sequencing. With the genomic data of Haemoproteus tartakovskyi as a reference, we successfully sequenced up to 1000 genes from each of the 15 selected samples belonging to nine different cytochrome b lineages, eight of which belong to Haemoproteus and one to Plasmodium. The targeted sequences were enriched to ～10⁴-fold, and mixed infections were identified as well as the proportions of each mixed lineage. We found that the total number of reads and the proportions of exons sequenced decreased when the parasite lineage became more divergent from the reference genome. For each of the samples, the recovery of sequences from different exons varied with the function and GC content of the exon. From the obtained sequences, we detected within-lineage variation in both mitochondrial and nuclear genes, which may be a result of local adaptation to different host species and environmental conditions. This targeted sequence capture protocol can be applied to a broader range of species and will open a new door for further studies on disease diagnostics and comparative analysis of haemosporidians evolution.     

On the origin of coding sequences from random open reading frames

Summary The size distribution of 411 randomly selected mammalian exons was investigated. This distribution was found to be unimodal with a frequency maximum of 120 bp. Detailed analysis of the distribution demonstrated that larger exons (>150 bp) have a high goodness of fit to the size distribution of open reading frames (ORFs) in a random sequence, i.e., (61/64)^t in which t is the number of triplets. Based on this observation, the general character of the total exon size distribution suggested that this could be defined by a theoretical distribution by superimposing a sigmoid function on the ORF generating function, i.e., (61/64)^t×f_s(t)×E in which f_s(t) is a sigmoid function and E is a constant. We tested this distribution for fitness to the exon distribution using two sigmoid functions. f_s(t)=(t) and f_s(t)=Be^kt/1+Be^kt. In both cases a very high goodness of fit was attained. It is concluded that exons have been generated from ORFs in random sequences, that ORFs larger than 150 bp have been selected, irrespective of size, as exons, and that a lower size limit exists below which the probability of an ORF being selected as an exon is very low. These results provide evidence at the molecular level to support the ideas that (1) larger exons have been selected from random ORFs without primary correlation to structural or functional properties at the protein level, (2) there exists a restriction on smaller ORFs to be selected as exons, and (3) the interrupted coding sequences found in eukaryotes represent the ancient form of gene organization that existed prior to the divergence of prokaryotes and eukaryotes.     

Ecosystem stress and health: an expansion of the conceptual basis

The assessment of the ecosystem health and departures from it requires clarity of what the system, its structure, dynamics, and healthy conditions are. Available definitions provide inadequate tools to acquire this clarity and may lead to arbitrary diagnoses of ecosystem health but such diagnoses can be overturned on a variety of scientific, philosophical, or political grounds.Nested hierarchy of ecosystem structure compounds the difficulty in the assessment of stress and health because both states may occur simultaneously at different hierarchical levels: with stress at one level being a necessary condition of health at another.An approach based on a formal definition of system change is advanced. First, a conceptual model identifies a self-maintaining minimum interactive structure (MIS) at each level of ecosystem organization. Components of MIS are complementary, coordinated, and exchanging information — they are integrated. Function is defined as a contribution of a component to the maintenance of the whole. In this context health is viewed as persistence of the system at a given temporal and spatial scale. Impairment of the function is stress and is contrasted with change of system structure (loss, addition, or replacement of components of MIS) which is disturbance. Stress can be measured directly by changes of function or indirectly by changes in integration. Even though undesirable from the human point of view, a changed system may again be considered healthy.     

Domestic exotics and the perception of invasibility

Susceptibility of an area to invasion by exotic species is often judged by the fraction of introduced species in the local biota. However, the degree of invasion, particularly in mainland areas, has often been underestimated because of the exclusion of ‘domestic exotics’ (those introduced to internal units from within the national border) in calculations. Because all introduced species on islands are considered as exotics, this contributes to the perception that islands are more susceptible to invasion than are continental regions. Here, we determine the contribution of domestic exotic species to the degree of invasion (exotic fraction) in mainland areas. We quantify the relationships of exotic fraction to the area, human population density and land use within each of the 48 conterminous US states to identify mechanisms that potentially influence the degree of invasion. For each of the 48 conterminous US states, we compiled the number of species introduced from outside the United States (‘foreign exotics’) and the number of exotics introduced from other conterminous US states (‘domestic exotics’). The status of each species as foreign or domestic was determined for each state by researching its precise origins through vouchered herbarium records, supplemented by literature ( Kartesz, 2010 ). We found that (1) the exotic fraction inevitably decreases with increasing area as the pool of potential exotic species decreases; (2) exotic richness of areas within large mainland regions is underestimated to the extent that species introduced among areas within a region are considered as natives; and (3) human activities contribute disproportionately more exotics to smaller than to larger administrative areas. How we define ‘exotic’ influences how we count non‐native species and perceive invasibility. Excluding domestic exotics in mainland regions leads to a biased perception of increased invasibility on islands, where all introduced species are considered exotic. Thus, future documentation and interpretation of invasion patterns and management of exotics should account for these biases in quantifying the exotic fraction.     

The circular definition of populations and its implications for biological sampling

Application of population-based theoretical models to the study of real world populations requires the relationship between the real and theoretical populations to be defined. Otherwise, it is not possible to take a representative field sample or census of a population. I demonstrate that the concept of a biological population is based on a circular definition and is logically untenable. A population is composed of a number of individuals whose membership of the population is determined by their relationship to the rest of the population. This has serious implications for common practice in a range of ecological and evolutionary disciplines.