Annual Review of Genetics - Volume 44, 2010

Plants have evolved sophisticated systems to cope with herbivore challenges. When plants perceive herbivore-derived physical and chemical cues, such as elicitors in insects' oral secretions and compounds in oviposition fluids, plants dramatically reshape their transcriptomes, proteomes, and metabolomes. All these herbivory-induced changes are mediated by elaborate signaling networks, which include receptors/ sensors, Ca²⁺ influxes, kinase cascades, reactive oxygen species, and phytohormone signaling pathways. Furthermore, herbivory induces defense responses not only in the wounded regions but also in undamaged regions in the attacked leaves and in distal intact (systemic) leaves. Here, we review recent progress in understanding plant perception of herbivory and oviposition, and the herbivory-induced early signaling events and their biological functions. We consider the intraspecific phenotypic diversity of plant responses to herbivory and discuss the underlying genetic variation. We also discuss new tools and technical challenges in studying plant-herbivore interactions.

The need for new antibiotic therapies is acute and growing in large part because of the emergence of drug-resistant pathogens. A vast number of resistance determinants are, however, found in nonpathogenic micro-organisms. The resistance totality in the global microbiota is the antibiotic resistome and includes not only established resistance genes but also genes that have the potential to evolve into resistance elements. We term these proto-resistance genes and hypothesize that they share common ancestry with other functional units known as housekeeping genes. Genomic enzymology is the study of protein structure–function in light of genetic context and evolution of protein superfamilies. This concept is highly applicable to study of antibiotic resistance evolution from proto-resistance elements. In this review, we summarize some of the genomic enzymology evidence for resistance enzymes pointing to common ancestry with genes of other metabolic functions. Genomic enzymology plays a key role in understanding the origins of antibiotic resistance and aids in designing strategies for diagnosis and prevention thereof.

In order to mitigate climate change without adversely affecting global energy supply, there is growing interest in the possibility of producing transportation fuels from renewable sources via microbial fermentation. Central to this challenge is the design of biocatalysts that can efficiently convert cheap lignocellulosic raw materials into liquid fuels. Owing to the wealth of genetic and metabolic knowledge associated with Escherichia coli, this bacterium is the most convenient starting point for engineering microbial catalysts for biofuel production. Here, we review the range of liquid fuels that can be produced in E. coli and discuss the underlying biochemistry that enables these metabolic products. The fundamental and technological challenges encountered in the development of efficient fermentation processes for biofuel production are highlighted. The example of biodiesel is a particularly illustrative case study and is therefore discussed in detail.

Bacteria have developed remarkable systems that sense neighboring target cells upon contact and initiate a series of events that enhance their survival and growth at the expense of the target cells. Four main classes of bacterial cell surface structures have been identified that interact with prokaryotic or eukaryotic target cells to deliver DNA or protein effectors. Type III secretion systems (T3SS) use a flagellum-like tube to deliver protein effectors into eukaryotic host cells, whereas Type IV systems use a pilus-based system to mediate DNA or protein transfer into recipient cells. The contact-dependent growth inhibition system (CDI) is a Type V system, using a long β-helical cell surface protein to contact receptors in target cells and deliver a growth inhibitory signal. Type VI systems utilize a phage-like tube and cell puncturing device to secrete effector proteins into both eukaryotic and prokaryotic target cells.

Sex chromosomes have many unusual features relative to autosomes. Y (or W) chromosomes lack genetic recombination, are male- (female-) limited, and show an abundance of genetically inert heterochromatic DNA but contain few functional genes. X (or Z) chromosomes also show sex-biased transmission (i.e., X chromosomes show female-biased and Z-chromosomes show male-biased inheritance) and are hemizygous in the heterogametic sex. Their unusual ploidy level and pattern of inheritance imply that sex chromosomes play a unique role in many biological processes and phenomena, including sex determination, epigenetic chromosome-wide regulation of gene expression, the distribution of genes in the genome, genomic conflict, local adaptation, and speciation. The vast diversity of sex chromosome systems in insects—ranging from the classical male heterogametic XY system in Drosophila to ZW systems in Lepidoptera or mobile genes determining sex as found in house flies—implies that insects can serve as unique model systems to study various functional and evolutionary aspects of these different processes.

Homologous recombination (HR) is required for accurate chromosome segregation during the first meiotic division and constitutes a key repair and tolerance pathway for complex DNA damage, including DNA double-strand breaks, interstrand crosslinks, and DNA gaps. In addition, recombination and replication are inextricably linked, as recombination recovers stalled and broken replication forks, enabling the evolution of larger genomes/replicons. Defects in recombination lead to genomic instability and elevated cancer predisposition, demonstrating a clear cellular need for recombination. However, recombination can also lead to genome rearrangements. Unrestrained recombination causes undesired endpoints (translocation, deletion, inversion) and the accumulation of toxic recombination intermediates. Evidently, HR must be carefully regulated to match specific cellular needs. Here, we review the factors and mechanistic stages of recombination that are subject to regulation and suggest that recombination achieves flexibility and robustness by proceeding through metastable, reversible intermediates.

Integrons are genetic elements able to acquire and rearrange open reading frames (ORFs) embedded in gene cassette units and convert them to functional genes by ensuring their correct expression. They were originally identified as a mechanism used by Gram-negative bacteria to collect antibiotic resistance genes and express multiple resistance phenotypes in synergy with transposons. More recently, their role has been broadened with the discovery of chromosomal integron (CI) structures in the genomes of hundreds of bacterial species. This review focuses on the resources carried in these elements, on their unique recombination mechanisms, and on the different mechanisms controlling the cassette dynamics. We discuss the role of the toxin/antitoxin (TA) cassettes for the stabilization of the large cassette arrays carried in the larger CIs, known as superintegrons. Finally, we explore the central role played by single-stranded DNA in the integron cassette dynamics in light of the recent discovery that the integron integrase expression is controlled by the SOS response.

Antisense RNAs encoded on the DNA strand opposite another gene have the potential to form extensive base-pairing interactions with the corresponding sense RNA. Unlike other smaller regulatory RNAs in bacteria, antisense RNAs range in size from tens to thousands of nucleotides. The numbers of antisense RNAs reported for different bacteria vary extensively, but hundreds have been suggested in some species. If all of these reported antisense RNAs are expressed at levels sufficient to regulate the genes encoded opposite them, antisense RNAs could significantly impact gene expression in bacteria. Here, we review the evidence for these RNA regulators and describe what is known about the functions and mechanisms of action for some of these RNAs. Important considerations for future research as well as potential applications are also discussed.

Changing a single nucleotide in a genome can have profound consequences under some conditions, but the same change can have no consequences under others. Indeed, organisms can be surprisingly robust to environmental and genetic perturbations. Yet, the mechanisms underlying such robustness are controversial. Moreover, how they might affect evolutionary change remains enigmatic. Here, we review the recently appreciated central role of protein homeostasis in buffering and potentiating genetic variation and discuss how these processes mediate the critical influence of the environment on the relationship between genotype and phenotype. Deciphering how robustness emerges from biological organization and the mechanisms by which it is overcome in changing environments will lead to a more complete understanding of both fundamental evolutionary processes and diverse human diseases.

The medaka fish, Oryzias latipes, is an emerging vertebrate model and now has a high quality draft genome and a number of unique mutants. The long history of medaka research in Japan has provided medaka with unique features, which are complementary to other vertebrate models. A large collection of spontaneous mutants collected over a century, the presence of highly polymorphic inbred lines established over decades, and the recently completed genome sequence all give the medaka a big boost. This review focuses on the state of the art in medaka genetics and genomics, such as the first isolation of active transposons in vertebrates, the influence of chromatin structure on sequence variation, fine quantitative trait locus (QTL) analysis, and versatile mutants as human disease models.

What really defines a telomere? Telomere literally is an amalgamation of the Greek words “telos,” meaning end, and “mer,” meaning part. In practice, it refers to the extremities of linear chromosomes. The defining functions of chromosome extremities can be summarized in two main categories. First, chromosome ends trick the cell into not identifying them as damage-induced double-strand DNA breaks (DSBs). An internal DSB immediately triggers cell-cycle arrest and is repaired to ensure that genome integrity remains undisturbed. Chromosome ends disguise themselves using assorted strategies, tailored to evade specific cellular responses. The second defining function of chromosome extremities involves self-preservation. Due to the inherent limitations of the canonical replication machinery, chromosomes gradually lose terminal DNA with successive rounds of replication. Telomeres have evolved tactics to circumvent this loss and to preserve themselves. This review focuses on highlights of telomeric strategies surrounding these two primary tasks, and finishes by discussing evidence that the full telomeric functional repertoire has yet to be defined.

Arbuscular mycorrhizal symbioses occur between fungi and the majority of plant species. They are important for plant nutrition, plant growth, protection from pathogens, plant diversity, nutrient cycling, and ecosystem processes. A key goal in research is to understand the molecular basis of the establishment, regulation, and functioning of the symbiosis. However, lack of knowledge on the genetics of the fungal side of this association has hindered progress. Here, we show how several key, recently discovered processes concerning the genetics of arbuscular mycorrhizal fungi could be essential for ultimately understanding the molecular genetics of this important symbiosis with plants.

There has been increasing interest in rare variants and their association with disease, and several rare variant–disease associations have already been detected. The usual association tests for common variants are underpowered for detecting variants of lower frequency, so alternative approaches are required. In addition to reviewing the association analysis methods for rare variants, we discuss the limitations of genome-wide association studies in identifying rare variants and the problems that arise in the imputation of rare variants.

In the last five years, canine genetics has gone from map construction to complex disease deconstruction. The availability of a draft canine genome sequence, dense marker chips, and an understanding of the genome architecture has changed the types of studies canine geneticists can undertake. There is now a clear recognition that the dog system offers the opportunity to understand the genetics of both simple and complex traits, including those associated with morphology, disease susceptibility, and behavior.

In this review, we summarize recent findings regarding canine domestication and review new information on the organization of the canine genome. We discuss studies aimed at finding genes controlling morphological phenotypes and provide examples of the way such paradigms may be applied to studies of behavior. We also discuss the many ways in which the dog has illuminated our understanding of human disease and conclude with a discussion on where the field is likely headed in the next five years.

The processes underlying lignification, which for many years have been the near-exclusive purview of chemists and biochemists, have more recently been approached using both classical forward genetic screens and targeted reverse genetic approaches such as antisense suppression, RNAi, and characterization of insertional mutants. In this review, we provide an overview of the current understanding of lignin biosynthesis and structure, with emphasis on mutant and transgenic plants that have contributed to this knowledge. We also discuss ongoing work aimed at elucidating the relationship between lignin structure and function in vivo, as well as the phenotypic consequences arising from genetic manipulation of the lignin biosynthetic pathway.

Bacteria, like eukaryotes, employ cytoskeletal elements to perform many functions, including cell morphogenesis, cell division, DNA partitioning, and cell motility. They not only possess counterparts of eukaryotic actin, tubulin, and intermediate filament proteins, but they also have cytoskeletal elements of their own. Unlike the rigid sequence and structural conservation often observed for eukaryotic cytoskeletal proteins, the bacterial counterparts can display considerable diversity in sequence and function across species. Their wide range of function highlights the flexibility of core cytoskeletal protein motifs, such that one type of cytoskeletal element can perform various functions, and one function can be performed by different types of cytoskeletal elements.

The RecQ helicases are conserved from bacteria to humans and play a critical role in genome stability. In humans, loss of RecQ gene function is associated with cancer predisposition and/or premature aging. Recent experiments have shown that the RecQ helicases function during distinct steps during DNA repair; DNA end resection, displacement-loop (D-loop) processing, branch migration, and resolution of double Holliday junctions (dHJs). RecQ function in these different processing steps has important implications for its role in repair of double-strand breaks (DSBs) that occur during DNA replication and meiosis, as well as at specific genomic loci such as telomeres.

An internal time-keeping mechanism has been observed in almost every organism studied from archaea to humans. This circadian clock provides a competitive advantage in fitness and survival (18, 30, 95, 129, 137). Researchers have uncovered the molecular composition of this internal clock by combining enzymology, molecular biology, genetics, and modeling approaches. However, understanding the mechanistic link between the clock and output responses has been elusive. In three model organisms, Arabidopsis thaliana, Drosophila melanogaster, and Mus musculus, whole-genome expression arrays have enabled researchers to investigate how maintaining a time-keeping mechanism connects to an adaptive advantage. Here, we review the impacts transcriptomics have had on our understanding of the clock and how this molecular clock connects with system-level circadian responses. We explore the discoveries made possible by high-throughput RNA assays, the network approaches used to investigate these large transcript datasets, and potential future directions.

Genotype-to-phenotype mapping commonly focuses on two major classes of mutations: single nucleotide polymorphisms (SNPs) and copy number variation (CNV). Here, we discuss an underestimated third class of genotypic variation: changes in microsatellite and minisatellite repeats. Such tandem repeats (TRs) are ubiquitous, unstable genomic elements that have historically been designated as nonfunctional “junk DNA” and are therefore mostly ignored in comparative genomics. However, as many as 10% to 20% of eukaryotic genes and promoters contain an unstable repeat tract. Mutations in these repeats often have fascinating phenotypic consequences. For example, changes in unstable repeats located in or near human genes can lead to neurodegenerative diseases such as Huntington disease. Apart from their role in disease, variable repeats also confer useful phenotypic variability, including cell surface variability, plasticity in skeletal morphology, and tuning of the circadian rhythm. As such, TRs combine characteristics of genetic and epigenetic changes that may facilitate organismal evolvability.