Advances in Genetics (eBook)

Jeffrey C. Hall (Herausgeber)

eBook Download: EPUB

2007 | 1. Auflage
176 Seiten
Elsevier Science (Verlag)
978-0-08-049352-7 (ISBN)

Infos

The field of genetics is rapidly evolving and new medical breakthroughs are occuring as a result of advances in knowledge of genetics. This series continually publishes imporatnt reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines.

Inhalt

Cover 1
Contents 6
Contributors 8
Chapter 1: Rapidly Evolving Rab GTPase Paralogs and Reproductive Isolation in Drosophila 9
I. Introduction 10
II. Experimental Approaches 13
III. Influences of Rab9D on Viability of Hybrids Between D. melanogaster and Its Sibling Species 13
A. Inactivation of Rab9D reduces hybrid incompatibility 15
B. Fast rate of evolution of Rab9D 19
IV. Predictions of Functions for 6paRAB9 Proteins 22
V. General Considerations 24
References 28
Chapter 2: The Neurospora crassa Circadian Clock 33
I. Introduction 34
II. Neurospora as a Circadian Model System 35
III. The Molecular Machinery of the Neurospora Circadian Oscillator 36
A. The Neurospora circadian feedback loops 38
B. WC-1 and WC-2: The activators of frq transcription in the circadian negative feedback loop 41
C. FRQ and FRH: The negative elements in the circadian negative feedback loop 42
D. Inhibition of WCC by FFC and the role of WC phosphorylation 44
E. FRQ phosphorylation regulated by kinases and phosphatases determines its stability and is important for its role in the circadian negative feedback loop 46
F. Degradation of FRQ through the ubiquitin-proteasome system requires a conserved SCF-type ubiquitin ligase, SCFFWD-1 48
G. Conservation of eukaryotic circadian oscillators, from Neurospora to animals 49
IV. Temporal Input from the Environment 50
A. Light input into the circadian clock 51
B. Temperature input 59
V. Temporal Output from the Oscillator 62
VI. FRQ-Less Oscillators 64
VII. Conclusions 66
Acknowledgments 67
References 67
Chapter 3: Involvement of Homologous Recombination in Carcinogenesis 75
I. Introduction 76
II. HR Involvement in DNA Repair 77
III. HR and Carcinogenesis 79
A. RAD51 79
B. BRCA 80
C. ATM 80
D. Tp53 81
E. BLM 82
F. WRN 82
G. FANC 83
IV. Other Diseases Attributable to HR 83
V. Carcinogen-Induced HR in Experimental Systems 84
VI. Summary 87
Acknowledgments 88
References 88
Chapter 4: Mutational Analysis of the Ribosome 97
I. Introduction 98
II. Mutational Analysis of 16S rRNA Structure and Function 99
A. Mutations in the 5' major domain of 16S rRNA 99
B. Mutations in the central domain of 16S rRNA 100
C. Mutations in the 3' major domain of 16S rRNA 101
D. Mutations in the 3' minor domain of 16S rRNA 103
III. Mutational Analysis of 23S rRNA Structure and Function 105
A. Mutations in Domain I of 23S rRNA 105
B. Mutations in domains II-IV of 23S rRNA 105
C. Mutations in domain V of 23S rRNA 106
D. Mutations in domain VI of 23S rRNA 110
IV. Mutational Analysis of Ribosomal Protein Structure and Function 111
A. Mutations in small-subunit proteins 111
B. Mutations in large-subunit proteins 113
V. Mutational Analysis of Ribosomal Factor Structure and Function 114
A. Mutations in initiation factors 114
B. Mutations in elongation factors 115
C. Mutations in release factors 116
D. Mutations in ribosome recycling factor 116
VI. Concluding Remarks 116
Acknowledgments 117
References 117
Chapter 5: Application of Genomics to Molecular Breeding of Wheat and Barley 129
I. Introduction 130
II. Molecular Markers and Marker-Assisted Breeding 131
A. Functional molecular markers 132
B. Status of marker-assisted breeding 136
C. Whole-genome breeding 137
III. Genomic Resources and Approaches 139
A. Transcriptome analysis 139
B. Functional genomics 141
C. Expression genetics and eQTLs 143
IV. Comparative Genomics 145
V. Exploitation of Natural Variation and Allelic Diversity 146
A. Advanced backcross QTL analysis 147
B. Association mapping based on linkage disequilibrium 149
VI. Concluding Remarks 151
References 152
Index 165

Textauszug

1

Rapidly Evolving Rab GTPase Paralogs and Reproductive Isolation in Drosophila

Pierre Hutter    Division of Genetics, Institut Central des Hôpitaux Valaisans, Avenue Grand-Champsec 86, 1951 Sion, Switzerland

Abstract

Alterations at the X-linked Hmr gene of Drosophila melanogaster can fully restore viability and partially restore fertility in hybrid flies from crosses between D. melanogaster and any of its three most closely related species. Although more than one gene is expected to be involved in these barriers to reproduction, a single DNA-binding protein was recently identified as HMR. The Hmr gene was shown to evolve unusually fast, a feature that supports its role in causing genetic incompatibility in a hybrid genotype. The current treatment of hybrid genetics focuses not only on Hmr but also on the Rab9D gene, which lies only 1 kb from Hmr. Rab9D is proposed also to influence hybrid viability. This gene has remained tightly linked to Hmr for about 10 million years, but it has diverged even more than Hmr with regard to D. melanogaster and its most closely related species. Furthermore, the 197-amino acid RAB9D protein contains four amino acid substitutions in the D. melanogaster-rescuing mutant Hmr1. Rab9D is shown to have evolved under very strong positive selection and to be the most recent member of a cluster of six paralogs that encode small RAB GTPases. Four of the six paralogs are unique to D. melanogaster in which they have diverged considerably, their encoded proteins sharing less than 50% amino acid identities with proteins from their orthologs in the closest species. Only two Rab orthologs are present in these sibling species and none is present in the genomes of more distantly related Drosophila species. Rapidly evolving Rab paralogs near the Hmr locus probably developed functional specialization of redundant proteins involved in trafficking macromolecules between cytoplasm and nucleus. Positive selection acting on duplicates of these Rab genes appears to participate in reproductive isolation.

I Introduction

It has often been argued that Darwin did not solve the issue of “The Origin of Species” because small genetic variations can only account for differences between populations within a species and not account for divergence between species by macroevolution. Findings discussed here support the view that gene duplication, an event relevant to macroevolution, together with classical Darwinian microevolution, may be instrumental in the process of reproductive isolation. Indeed, a high rate of evolution of genes involved in reproductive isolation can be facilitated when these involve paralogs that are subject to less selective constraints than the parental form.

According to the biological species concept formulated by Mayr (1943), the creation of a new species requires that members of a population build up their own gene pool after becoming reproductively isolated from other members of the parental species. In organisms produced by crosses between populations in the state of incipient speciation, genetics posits that barriers to gene flow, such as lethality or sterility, result from genetic factors that exhibit functional incompatibilities. In hybrids between sibling species that have since long become distinct biological entities, it is difficult to identify, a posteriori, which of the genes associated with hybrid incompatibility (HI) actually reflect the primary factors that were instrumental to the initiation of speciation.

While both Cordon and Kosswig proposed as early as 1927 the concept of genetic HI in the fish genus Xiphophorus, entry points for experimental studies on this major biological issue only emerged over the last 25 years (Cordon, 1927; Kosswig, 1927). A handful of observations have indicated that single genetic changes can drastically influence reproductive isolation between most closely related species. The first mutations that can break through reproductive isolation were reported in organisms amenable to genetic analysis, such as Lhr and mhr in Drosophila simulans (Sawamura et al., 1993a; Watanabe, 1979), as well as Hmr and Zhr in D. melanogaster (Hutter and Ashburner, 1987; Hutter et al., 1990; Sawamura et al., 1993b). These genetic changes are sufficient to restore full viability in otherwise completely inviable hybrids, and some of these alterations also partly restore female fertility. Similarly, mutations in otherwise fully fertile flies were found to play a significant role in causing sterility of hybrids between Drosophila species (see Wu and Ting, 2004 for a review). Because genetic alterations responsible for these rescues have no phenotypic effect within a given species, they are thought to reflect incompatibilities in hybrid genotypes having to do with genes that have diverged functionally.

As Coyne and Orr (2004) emphasized, the first molecular studies of these genes strongly suggested that they represent the actual genes that cause the death or the sterility of hybrids rather than being second-site suppressors that might ameliorate effects of the loci causing hybrid problems. Thus, these genetic alterations influencing HI are our best candidates to explore the scenario of reproductive isolation based on a minimum of two genes, as originally envisioned by Dobzhansky (1937) and Müller (1940). Noteworthy, in D. melanogaster all mutations that rescue otherwise lethal hybrids were found in genes of the X chromosome, and previous studies in other Drosophila species have also indicated a major effect of the X chromosome on hybrid inviability (reviewed in Hutter, 1997). Genes that cause HI as a result of positive selection are predicted to be often X-linked, as recessive X-linked alleles can become fixed more quickly than autosomal genes and are likely to evolve rapidly (Charlesworth et al., 1987).

Under laboratory conditions, D. melanogaster can hybridize with its three most closely related species, D. simulans, D. mauritiana, and D. sechellia (hereafter referred to as the sibling species), even though the latter species have diverged from an ancestor of D. melanogaster approximately 2–3 million years (Myr) ago (Lachaise et al., 1988). However, crosses between D. melanogaster females and males of any of its three sibling species produce hybrid daughters that are viable but sterile at low temperatures and lethal at high temperatures. Hybrid sons invariably die as late larvae or pseudopupae and never metamorphose (Hadorn, 1961; Hutter et al., 1990; Lachaise et al., 1988; Sturtevant, 1920). Three D. melanogaster mutants—Hmr1, In(1)AB, and Df(1)EP307–1-2—were found to rescue otherwise lethal hybrids, and all three mutations map to cytological interval 9D–9E in the middle of the X chromosome (Barbash et al., 2000, 2004b; Hutter and Ashburner, 1987; Hutter et al., 1990). The first two mutations not only rescue lethal hybrids, but also contribute to restore fertility in otherwise sterile hybrid females (Barbash and Ashburner, 2003).

During recent years, three studies have addressed the molecular basis of the genetic factors capable to suppress the invariant lethality of hybrids. The first report postulated that a cluster of six paralogs in D. melanogaster, which encode RAB GTPase proteins, is involved in HI between members of the D. melanogaster subgroup species (Hutter, 2002). Sexually antagonistic coevolution between the Rab paralogs and extranuclear components were hypothesized to result in fast evolution of genes involved in vesicle trafficking and cell signaling. The second molecular study, based on transgenesis experiments, identified a single gene as Hmr (Barbash et al., 2003), lying in the middle of the above cluster of six Rab paralogs. Hmr encodes a regulatory protein with homology to a family of MADF- and MYB-related DNA-binding transcriptional regulators and was shown to be evolving particularly fast as a result of strong positive selection (Barbash et al., 2003, 2004a). Indeed, an unusually high average divergence rate of 7.7% for nonsynonymous nucleotide substitutions [leading to amino acid (AA) replacements] was observed in HMR protein between D. melanogaster and its sibling species. Nonetheless, in In(1)AB and Df(1)EP307–1-2 D. melanogaster mutants which rescue the same interspecific hybrids as Hmr1 does, no causative mutation has yet been attributed to Hmr. This gene appears normally transcribed in both above-mentioned mutants by Northern analysis (Barbash et al., 2003). The third molecular study on HI in Drosophila, based on complementation mapping of HI genes between D. melanogaster and D. simulans, identified a gene called Nup96, on the third chromosome of...

Produkt-Details

• Erscheint lt. Verlag: 7.5.2007
• Sprache: englisch
• Themenwelt: Sachbuch/Ratgeber
• Themenwelt: Studium ► Querschnittsbereiche ► Epidemiologie / Med. Biometrie
• Themenwelt: Naturwissenschaften ► Biologie ► Genetik / Molekularbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Technik
• ISBN-10: 0-08-049352-1 / 0080493521
• ISBN-13: 978-0-08-049352-7 / 9780080493527