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PubMed2026

Genome-wide identification, characterization, evolutionary analysis, and expression profiling of the FCS-like zinc finger (FLZ) gene family in soybean (Glycine max L.) under abiotic stresses.

Drought and salinity limit soybean yield. Despite their role in the SnRK1 energy-sensing complex, a systematic study of FCS-Like Zinc Finger (FLZ) proteins in soybean has not been reported. We performed a genome-wide identification of the GmFLZ gene family, identifying 40 members distributed across 18 of the 20 soybean chromosomes. Phylogenetic analysis of 87 FLZ proteins from Glycine max, Arabidopsis thaliana, and Oryza sativa revealed four major evolutionary clades, suggesting that diversification predates the separation of monocots and dicots. Structural analysis identified ten conserved motifs, with Motifs 1 and 2 present in all family members. Gene duplication analysis identified 304 paralogous pairs, most arising from segmental duplication. Ka/Ks analysis indicated localized positive selection in six gene pairs and purifying selection in 97.9% of pairs. Tissue-specific expression profiling across nine tissues showed that GmFLZ5, GmFLZ15, GmFLZ25, and GmFLZ34 had the highest expression levels detected across the GmFLZ family, with GmFLZ5 the most highly expressed member in leaves, nodules, and stem and showing moderate expression in pod, root, and root hairs, whereas GmFLZ18, GmFLZ23, and GmFLZ37 showed root-preferential expression. RT-qPCR validation under drought (20% PEG-6000) and salt (200 mM NaCl) treatments in the Giza 5 cultivar showed that 36 and 34 of the 40 GmFLZ genes, respectively, exhibited at least a two-fold change in expression, with GmFLZ21 and GmFLZ35 among the most strongly induced under salt stress. These findings provide an evolutionary and functional framework for the GmFLZ family and identify candidate genes for future functional studies in soybean stress tolerance.

Glycine max↗

PubMed2001

Evolution of genome-phenome diversity under environmental stress.

The genomic era revolutionized evolutionary biology. The enigma of genotypic-phenotypic diversity and biodiversity evolution of genes, genomes, phenomes, and biomes, reviewed here, was central in the research program of the Institute of Evolution, University of Haifa, since 1975. We explored the following questions. (i) How much of the genomic and phenomic diversity in nature is adaptive and processed by natural selection? (ii) What is the origin and evolution of adaptation and speciation processes under spatiotemporal variables and stressful macrogeographic and microgeographic environments? We advanced ecological genetics into ecological genomics and analyzed globally ecological, demographic, and life history variables in 1,200 diverse species across life, thousands of populations, and tens of thousands of individuals tested mostly for allozyme and partly for DNA diversity. Likewise, we tested thermal, chemical, climatic, and biotic stresses in several model organisms. Recently, we introduced genetic maps and quantitative trait loci to elucidate the genetic basis of adaptation and speciation. The genome-phenome holistic model was deciphered by the global regressive, progressive, and convergent evolution of subterranean mammals. Our results indicate abundant genotypic and phenotypic diversity in nature. The organization and evolution of molecular and organismal diversity in nature at global, regional, and local scales are nonrandom and structured; display regularities across life; and are positively correlated with, and partly predictable by, abiotic and biotic environmental heterogeneity and stress. Biodiversity evolution, even in small isolated populations, is primarily driven by natural selection, including diversifying, balancing, cyclical, and purifying selective regimes, interacting with, but ultimately overriding, the effects of mutation, migration, and stochasticity.

Animals↗

PubMed1983

Growth performance and intestinal transit time of rats fed purified and natural dietary fibers.

The effects of some selected purified fibers were compared to those derived from cereals or legume seeds. Rats were fed for at least 9 weeks and measurements were taken to determine feed consumption, weight gain, feed efficiency ratios (FER), protein efficiency ratios (PER), apparent protein digestibility, and rate of transit through the gastrointestinal tract. Most diets were designed to contain approximately 10% dietary fiber and 10% protein. Compared to the fiber-free diet, pectin reduced weight gain, FER, PER and apparent protein digestibility values. Cellulose, xylan and raffinose had no influence on feed intake, weight gains or FERs. However, cellulose and xylan increased PER values and the rates of food passage but decreased the apparent protein digestibility values. Feed utilization, protein digestibility and growth were similar for the wheat bran, corn bran and fiber-free diets. These cereal fibers caused the rates of transit to be significantly increased relative to the fiber-free control diet. The hull and cell-wall-fiber fractions of beans, when compared to the fiber-free diet, had little effect on feed consumption, growth, FER or PER. The cell-wall-fiber fraction reduced apparent protein digestibility and the hull fraction accelerated food passage relative to the fiber-free diet.

Animals↗

PubMed1997

Molecular evolution of cytochrome c oxidase subunit IV: evidence for positive selection in simian primates.

Cytochrome c oxidase (COX) is a multi-subunit enzyme complex that catalyzes the final step of electron transfer through the respiratory chain on the mitochondrial inner membrane. Up to 13 subunits encoded by both the mitochondrial (subunits I, II, and III) and nuclear genomes occur in eukaryotic organisms ranging from yeast to human. Previously, we observed a high number of amino acid replacements in the human COX IV subunit compared to mouse, rat, and cow orthologues. Here we examined COX IV evolution in the two groups of anthropoid primates, the catarrhines (hominoids, cercopithecoids) and platyrrhines (ceboids), as well as one prosimian primate (lorisiform), by sequencing PCR-amplified portions of functional COX4 genes from genomic DNAs. Phylogenetic analysis of the COX4 sequence data revealed that accelerated nonsynonymous substitution rates were evident in the early evolution of both catarrhines and, to a lesser extent, platyrrhines. These accelerated rates were followed later by decelerated rates, suggesting that positive selection for adaptive amino acid replacement became purifying selection, preserving replacements that had occurred. The evidence for positive selection was especially pronounced along the catarrhine lineage to hominoids in which the nonsynonymous rate was first faster than the synonymous rate, then later much slower. The rates of three types of "neutral DNA" nucleotide substitutions (synonymous substitutions, pseudogene nucleotide substitutions, and intron nucleotide substitutions) are similar and are consistent with previous observations of a slower rate of such substitutions in the nuclear genomes of hominoids than in the nuclear genomes of other primate and mammalian lineages.

Amino Acid Sequence↗

PubMed2004

Selective pressures on the olfactory receptor repertoire since the human-chimpanzee divergence.

The availability of the sequence of the chimpanzee genome provides an opportunity to examine human genes and their chimpanzee orthologs and to analyze selective pressures that have been shaping the olfactory receptor repertoire since the human-chimpanzee divergence. We determined the ratio of nonsynonymous to synonymous changes for each of 186 orthologous pairs and then examined how the distribution of these ratios compares with the distribution expected under neutral drift. Consistent with the diminishing importance of olfaction for these species, we find no evidence for positive selection and we find evidence of weak purifying selection affecting over half of the repertoire.

Animals↗

PubMed2000

Deletion of a conserved regulatory element in the Drosophila Adh gene leads to increased alcohol dehydrogenase activity but also delays development.

In vivo levels of enzymatic activity may be increased through either structural or regulatory changes. Here we use Drosophila melanogaster alcohol dehydrogenase (ADH) in an experimental test for selective differences between these two mechanisms. The well-known ADH-Slow (S)/Fast (F) amino acid replacement leads to a twofold increase in activity by increasing the catalytic efficiency of the enzyme. Disruption of a highly conserved, negative regulatory element in the Adh 3' UTR also leads to a twofold increase in activity, although this is achieved by increasing in vivo Adh mRNA and protein concentrations. These two changes appear to be under different types of selection, with positive selection favoring the amino acid replacement and purifying selection maintaining the 3' UTR sequence. Using transgenic experiments we show that deletion of the conserved 3' UTR element increases adult and larval Adh expression in both the ADH-F and ADH-S genetic backgrounds. However, the 3' UTR deletion also leads to a significant increase in developmental time in both backgrounds. ADH allozyme type has no detectable effect on development. These results demonstrate a negative fitness effect associated with Adh overexpression. This provides a mechanism whereby natural selection can discriminate between alternative pathways of increasing enzymatic activity.

3' Untranslated Regions↗

PubMed2006

Evaluation of whether accelerated protein evolution in chordates has occurred before, after, or simultaneously with gene duplication.

Gene duplication and loss are predicted to be at least of the order of the substitution rate and are key contributors to the development of novel gene function and overall genome evolution. Although it has been established that proteins evolve more rapidly after gene duplication, we were interested in testing to what extent this reflects causation or association. Therefore, we investigated the rate of evolution prior to gene duplication in chordates. Two patterns emerged; firstly, branches, which are both preceded by a duplication and followed by a duplication, display an elevated rate of amino acid replacement. This is reflected in the ratio of nonsynonymous to synonymous substitution (mean nonsynonymous to synonymous nucleotide substitution rate ratio [Ka:Ks]) of 0.44 compared with branches preceded by and followed by a speciation (mean Ka:Ks of 0.23). The observed patterns suggest that there can be simultaneous alteration in the selection pressures on both gene duplication and amino acid replacement, which may be consistent with co-occurring increases in positive selection, or alternatively with concurrent relaxation of purifying selection. The pattern is largely, but perhaps not completely, explained by the existence of certain families that have elevated rates of both gene duplication and amino acid replacement. Secondly, we observed accelerated amino acid replacement prior to duplication (mean Ka:Ks for postspeciation preduplication branches was 0.27). In some cases, this could reflect adaptive changes in protein function precipitating a gene duplication event. In conclusion, the circumstances surrounding the birth of new proteins may frequently involve a simultaneous change in selection pressures on both gene-copy number and amino acid replacement. More precise modeling of the relative importance of preduplication, postduplication, and simultaneous amino acid replacement will require larger and denser genomic data sets from multiple species, allowing simultaneous estimation of lineage-specific fluctuations in mutation rates and adaptive constraints.

Amino Acid Substitution↗

PubMed1997

Molecular evolution of cytochrome c oxidase: rate variation among subunit VIa isoforms.

Cytochrome c oxidase (COX) consists of 13 subunits, 3 encoded in the mitochondrial genome and 10 in the nucleus. Little is known of the role of the nuclear-encoded subunits, some of which exhibit tissue-specific isoforms. Subunit VIa is unique in having tissue-specific isoforms in all mammalian species examined. We examined relative evolutionary rates for the COX6A heart (H) and liver (L) isoform genes along the length of the molecule, specifically in relation to the tissue-specific function(s) of the two isoforms. Nonsynonymous (amino acid replacement) substitutions in the COX6AH gene occurred more frequently than in the ubiquitously expressed COX6AL gene. Maximum-parsimony analysis and sequence divergences from reconstructed ancestral sequences revealed that after the ancestral COX6A gene duplicated to yield the genes for the H and L isoforms, the sequences encoding the mitochondrial matrix region of the COX VIa protein experienced an elevated rate of nonsynonymous substitutions relative to synonymous substitutions. This is expected for relaxed selective constraints after gene duplication followed by purifying selection to preserve the replacements with tissue-specific functions.

Amino Acid Sequence↗

PubMed2006

Regions of extreme synonymous codon selection in mammalian genes.

Recently there has been increasing evidence that purifying selection occurs among synonymous codons in mammalian genes. This selection appears to be a consequence of either cis-regulatory motifs, such as exonic splicing enhancers (ESEs), or mRNA secondary structures, being superimposed on the coding sequence of the gene. We have developed a program to identify regions likely to be enriched for such motifs by searching for extended regions of extreme codon conservation between homologous genes of related species. Here we present the results of applying this approach to five mammalian species (human, chimpanzee, mouse, rat and dog). Even with very conservative selection criteria, we find over 200 regions of extreme codon conservation, ranging in length from 60 to 178 codons. The regions are often found within genes involved in DNA-binding, RNA-binding or zinc-ion-binding. They are highly depleted for synonymous single nucleotide polymorphisms (SNPs) but not for non-synonymous SNPs, further indicating that the observed codon conservation is being driven by negative selection. Forty-three percent of the regions overlap conserved alternative transcript isoforms and are enriched for known ESEs. Other regions are enriched for TpA dinucleotides and may contain conserved motifs/structures relating to mRNA stability and/or degradation. We anticipate that this tool will be useful for detecting regions enriched in other classes of coding-sequence motifs and structures as well.

Alternative Splicing↗

PubMed1993

T cells and monocytes regulate the generation and functional activity of natural killer-derived lymphokine-activated killer cells.

The lymphokine-activated killer (LAK) phenomenon is generally referred to as nonspecific, i.e., major histocompatibility complex (MHC)-unrestricted cytotoxicity against tumor cells generated by ex vivo culture of human peripheral blood lymphocytes with interleukin 2 (IL-2). In this study, we selectively purified and depleted cell subpopulations such as natural killer (NK) cells, T-lymphocytes and monocytes from fresh human peripheral blood by negative selection. While highly purified NK cells could be induced to acquire potent LAK activity in five-day culture with IL-2, the presence of T-lymphocytes and monocytes in NK cultures was needed in order to induce a significant expansion of cytotoxic effector cells over the culture period. Neither T cells nor monocytes by themselves were able to generate LAK cells in a standard five-day IL-2 culture. However, when added to highly purified NK cells prior to IL-2 incubation, a proportion of CD3+ T-lymphocytes was found to gain LAK-like killing activity. Monocytes, when cultured with IL-2 in the presence of NK cells and T-lymphocytes, did not appear to acquire LAK activity but were able to induce a dramatic increase in cytotoxic lymphocyte recovery after five days with IL-2. In summary, we could demonstrate that peripheral blood T-lymphocytes and monocytes are potent regulators of NK-dependent lymphokine (IL-2)-activated killing.

Cell Communication↗

PubMed2026

First complete mitochondrial genome of Uzelothrips scabrosus (Thysanoptera: Uzelothripidae) provides insights into gene rearrangements and phylogenetic position within Terebrantia.

The family Uzelothripidae is represented by a single genus Uzelothrips and can be distinguished from others by the presence of whip-like antennae, a circular ventral sensorium on antennal segment III, a well-developed tentorium, and a membranous ovipositor. Here, we generated the first complete mitochondrial genome of Uzelothrips scabrosus (15,674 bp) using next-generation sequencing to explore the gene rearrangements and phylogenetic relationships. It consists of 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and two putative control regions. The genome exhibits strong AT bias (71.35%) with negative AT and GC skew. Codon usage analyses indicate a strong bias towards A/U-ending codons and influenced by both natural selection and mutation pressure. All PCGs were under purifying selection, with cox1 being the most conserved and nad4L the most variable. The gene order of the family Uzelothripidae is highly rearranged compared to the ancestral insect gene order. Comparative analysis revealed that gene block B was the most widely conserved, whereas the remaining gene blocks exhibited family or lineage-specific conservation patterns, reflecting extensive mitochondrial gene rearrangements during the evolution of the Thysanoptera. Moreover, 228 synapomorphic and 68 autapomorphic gene boundaries were identified across thysanopteran mitogenomes. Phylogenies indicated that the family Uzelothripidae is in a sister relationship with Stenurothripidae, and the Uzelothripidae + Stenurothripidae clade is sister to Thripidae. This study provides the first mitogenomic insights into Uzelothripidae and highlights the need for broader taxon sampling and nuclear genomic data to resolve deep evolutionary relationships within Thysanoptera.

Comparative analysis↗

PubMed2002

Natural selection at linked sites in humans.

Theoretical and empirical work indicates that patterns of neutral polymorphism can be affected by linked, selected mutations. Under background selection, deleterious mutations removed from a population by purifying selection cause a reduction in linked neutral diversity. Under genetic hitchhiking, the rise in frequency and fixation of beneficial mutations also reduces the level of linked neutral polymorphism. Here we review the evidence that levels of neutral polymorphism in humans are affected by selection at linked sites. We then discuss four approaches for distinguishing between background selection and genetic hitchhiking based on (i) the relationship between polymorphism level and recombination rate for neutral loci with high mutation rates, (ii) relative levels of variation on the X chromosome and the autosomes, (iii) the frequency distribution of neutral polymorphisms, and (iv) population-specific patterns of genetic variation. Although the evidence for selection at linked sites in humans is clear, current methods and data do not allow us to clearly assess the relative importance of background selection and genetic hitchhiking in humans. These results contrast with those obtained for Drosophila, where the signals of positive selection are stronger.

Africa↗

PubMed2002

Intraspecific molecular variation in the seaweed fly Coelopa frigida consistent with behavioural distinctness of British and Swedish populations.

The major aim of this study was to compare the intraspecific variation and genetic structure of the behaviourally distinct British and Swedish populations of the seaweed fly Coelopa frigida. C. frigida has been the subject of intense study into the basis of female choice. The behaviour of British females is consistent with a 'good genes' model, whereas that of the Swedish flies suggests a Fisher process, in which the difference between the former and the latter is defined by female choice increasing offspring viability in 'good genes' models. Through a study of variability in the mitochondrial cytochrome oxidase II gene from more than 600 flies, we show that there is clear differentiation at the molecular level between the two countries' populations, with an FST of > 75% and no shared haplotypes. Tajima's test reveals an excess of rare variants relative to expectation, which, if not the result of selective sweep, indicates either a population expansion or purifying selection against weakly deleterious variants. Within the two populations, substantial subpopulation differentiation is observed in the UK, where there is also evidence of isolation by distance. Swedish populations exhibit lower variability, and no evidence of isolation by distance, with the latter result possibly being related to the continuous distribution of suitable habitat. The pattern of intraspecific variation is explainable by a combination of contemporary and also historical factors. British and Swedish populations may have been descended from at least two separate founding populations during the recolonization of these areas following Pleistocene glaciations.

Alcohol Dehydrogenase↗

PubMed1990

Purified glucocorticoid receptors bind selectively in vitro to a cloned DNA fragment that mediates a delayed secondary response to glucocorticoids in vivo.

We have identified and characterized a 206-base-pair region downstream from rat alpha 2u-globulin promoter that specifically mediates a delayed secondary response to glucocorticoids. Unlike positive primary glucocorticoid response elements (GREs), this regulatory element, termed delayed sGRE, dictates an inductive process preceded by a time lag of several hours and blocked by the protein synthesis inhibitor cycloheximide. Reminiscent of GREs and negative GREs (nGREs), a delayed sGRE confers hormonal regulation upon a linked heterologous promoter from a downstream position with respect to transcription start site and, remarkably, also interacts selectively with purified glucocorticoid receptor. These results imply that receptor binding to a delayed sGRE in vivo may mediate certain secondary responses to glucocorticoid hormones.

Alpha-Globulins↗

PubMed2026

Pervasive positive selection on X-linked ampliconic genes in primates.

Mammalian sex chromosomes harbour ampliconic gene families, which are multi-copy genes with ≥97% sequence identity, predominantly expressed in testis tissue and essential for male fertility. The amplification of testis-specific genes is conserved across mammals, yet the specific gene families that expand show striking lineage-specific variation. Previous studies suggest a dynamic turnover with adaptive evolution for several of these families, but their analysis has been limited by the quality of reference genomes of repetitive regions. To characterise the molecular evolutionary processes of ampliconic gene families on both sex chromosomes, we analysed telomere-to-telomere genome assemblies from eight primate species spanning 25 million years of evolution. We identified 53 X-linked and 19 Y-linked ampliconic gene families with dynamic copy number variation. Gene conversion through palindromic pairing and tandem arrays maintained high sequence similarity despite accumulating mutations. X-linked families maintained conserved chromosomal positions despite copy number changes, whereas Y-linked families showed frequent positional turnover. Strikingly, multiple X-linked families (GAGE, SSX, CSAG, and VCX) showed pervasive positive selection across the primate phylogeny and multiple (MAGEB, CT45, HSFX) showed lineage specific positive selection. Y-linked families predominantly evolve under purifying selection. Examining intraspecific copy number variation of the X-linked ampliconic families in chimpanzees, humans, and gorillas, we found variation among individuals but clear differences between species, with the largest families varying the most. These patterns could suggest that sperm competition, meiotic drive, or dosage-dependent selection drive the rapid, lineage-specific evolution of testis-expressed ampliconic genes in primates.

Journal Article↗

PubMed2004

Molecular analysis of adenovirus isolates from vaccinated and unvaccinated young adults.

Infections of adenovirus type 4 (Ad4) and Ad7 were discovered among previously vaccinated individuals through febrile respiratory illness surveillance at military recruit camps. Genetic analysis was performed on these isolates and a sample of adenovirus isolates from unvaccinated patients. Antigenic regions of the adenovirus hexon gene from 21 vaccinated and 31 unvaccinated patients were sequenced and compared to homologous regions of Ad4 and Ad7 vaccine strains and of other representative hexon sequences archived in GenBank. The phylogenetic distribution of sequences from vaccinated individuals closely resembled those from unvaccinated individuals. The most common Ad7 strain was the Ad7d2 hexon genotype, and the most common Ad4 strain was a genotype nearly identical to the recently discovered Z-G 95-873 Ad4 variant. Near exclusive isolation of Ad4 since 1999 indicates that the Ad4 variant is currently responsible for the vast majority of adenovirus morbidity in military recruit camps. Different ratios of nonsynonymous to synonymous nucleotide substitution rates in known antigenic regions compared to nonantigenic regions indicated positive selection for diversity in the antigenic regions and purifying selection in the nonantigenic regions.

Adenovirus Infections, Human↗

PubMed2006

A large family of ancient repeat elements in the human genome is under strong selection.

Although conserved noncoding elements (CNEs) constitute the majority of sequences under purifying selection in the human genome, they remain poorly understood. CNEs seem to be largely unique, with no large families of similar elements reported to date. Here, we search for CNEs among the ancestral repeat classes in the human genome and report the discovery of a large CNE family containing >900 members. This family belongs to the MER121 class of repeats. Although the MER121 family members show considerable sequence variation among one another, the individual copies show striking conservation in orthologous locations across the human, dog, mouse, and rat genomes. The element is also present and conserved in orthologous locations in the marsupial, but its genome-wide dispersal postdates the divergence from birds. The comparative genomic data indicate that MER121 does not encode a family of either protein-coding or RNA genes. Although the precise function of these elements remains unknown, the evidence suggests that this unusual family may play a cis-regulatory or structural role in mammalian genomes.

Animals↗

PubMed2003

Tests for positive selection on immune and reproductive genes in closely related species of the murine genus mus.

We examine variation among species of Mus in four genes involved in reproduction and the immune response for evidence of positive selection: the sperm recognition gene Zp-3, the testis-determining locus Sry, the testicular cell surface matrix protein Tcp-1, and the immune system protein beta(2) m. We use likelihood ratio tests in the context of a well-supported phylogeny to determine whether models that allow for positively selected sites fit the sequences better than models that assume purifying selection. We then apply a Bayesian approach to identify particular sites in each gene that have a high posterior probability of being under positive selection. We find no evidence of positive selection on the Tcp-1 gene, but for Zp-3, Sry, and beta(2) m, models that allow for positively selected sites fit the sequences better than alternatives. For each of these genes, we identify sites that have a high (> 95%) posterior probability of being positively selected. For Zp-3, two of these sites occur near the sperm-binding region, while one occurs in a region whose functional role remains unstudied but where the pattern of change predicts functional importance. A single site in Sry shows an elevated rate of replacement substitution but occurs in a region of apparently little functional importance; therefore, relaxation of functional constraints may better explain the rapid evolution of this site. Three sites in beta(2) m have a posterior probability > 50% of being under positive selection. While the functional role for two of these sites is unknown, the third is known to influence the ability of MHC class I molecules to present antigens to the immune system; therefore, the elevated rate of replacement substitutions at this site is consistent with selection acting to promote variability in immune system proteins.

Animals↗