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PubMed2005

Phylogenetic detection of conserved gene clusters in microbial genomes.

BACKGROUND: Microbial genomes contain an abundance of genes with conserved proximity forming clusters on the chromosome. However, the conservation can be a result of many factors such as vertical inheritance, or functional selection. Thus, identification of conserved gene clusters that are under functional selection provides an effective channel for gene annotation, microarray screening, and pathway reconstruction. The problem of devising a robust method to identify these conserved gene clusters and to evaluate the significance of the conservation in multiple genomes has a number of implications for comparative, evolutionary and functional genomics as well as synthetic biology. RESULTS: In this paper we describe a new method for detecting conserved gene clusters that incorporates the information captured by a genome phylogenetic tree. We show that our method can overcome the common problem of overestimation of significance due to the bias in the genome database and thereby achieve better accuracy when detecting functionally connected gene clusters. Our results can be accessed at database GeneChords http://genomics10.bu.edu/GeneChords. CONCLUSION: The methodology described in this paper gives a scalable framework for discovering conserved gene clusters in microbial genomes. It serves as a platform for many other functional genomic analyses in microorganisms, such as operon prediction, regulatory site prediction, functional annotation of genes, evolutionary origin and development of gene clusters.

Algorithms↗
PubMed2004

Extreme conservation of noncoding DNA near HoxD complex of vertebrates.

BACKGROUND: Homeotic gene complexes determine the anterior-posterior body axis in animals. The expression pattern and function of hox genes along this axis is colinear with the order in which they are organized in the complex. This 'chromosomal organization and functional correspondence' is conserved in all bilaterians investigated. Genomic sequences covering the HoxD complex from several vertebrate species are now available. This offers a comparative genomics approach to identify conserved regions linked to this complex. Although the molecular basis of 'colinearity' of Hox complexes is not yet understood, it is possible that there are control elements within or in the proximity of these complexes that establish and maintain the expression patterns of hox genes in a coordinated fashion. RESULTS: We have compared DNA sequence flanking the HoxD complex of several primate, rodent and fish species. This analysis revealed an unprecedented conservation of non-coding DNA sequences adjacent to the HoxD complex from fish to human. Stretches of hundreds of base pairs in a 7 kb region, upstream of HoxD complex, show 100% conservation across the vertebrate species. Using PCR primers from the human sequence, these conserved regions could be amplified from other vertebrate species, including other mammals, birds, reptiles, amphibians and fish. Our analysis of these sequences also indicates that starting from the conserved core regions, more sequences have been added on and maintained during evolution from fish to human. CONCLUSION: Such a high degree of conservation in the core regions of this 7 kb DNA, where no variation occurred during approximately 500 million years of evolution, suggests critical function for these sequences. We suggest that such sequences are likely to provide molecular handle to gain insight into the evolution and mechanism of regulation of associated gene complexes.

Animals↗
PubMed1993

Conservation of regulatory elements controlling hairy pair-rule stripe formation.

The hairy (h) gene is one of two pair-rule loci whose striped expression is directly regulated by combinations of gap proteins acting through discrete upstream regulatory fragments, which span several kilobases. We have undertaken a comparative study of the molecular biology of h pair-rule expression in order to identify conserved elements in this complex regulatory system, which should provide important clues concerning the mechanism of stripe formation. A molecular comparison of the h locus in Drosophila virilis and Drosophila melanogaster reveals a conserved overall arrangement of the upstream regulatory elements that control individual pair-rule stripes. We demonstrate that upstream fragments from D. virilis will direct the proper expression of stripes in D. melanogaster, indicating that these are true functional homologs of the stripe-producing D. melanogaster regulatory elements, and that the network of trans-acting proteins that act upon these regulatory elements is highly conserved. We also demonstrate that the spatial relationships between specific h stripes and selected gap proteins are highly conserved. We find several tracts of extensive nucleotide sequence conservation within homologous stripe-specific regulatory fragments, which have facilitated the identification of functional subelements within the D. melanogaster regulatory fragment for h stripe 5. Some of the conserved nucleotide tracts within this regulatory fragment contain consensus binding sites for potential trans-regulatory (gap and other) proteins, while many appear devoid of known binding sites. This comparative approach, coupled with the analysis of reporter gene expression in gap mutant embryos suggests that the Kr and gt proteins establish the anterior and posterior borders of h stripe 5, respectively, through spatial repression. Other, as yet unidentified, proteins are certain to play a role in stripe activation, presumably acting through other conserved sequence tracts.

Amino Acid Sequence↗
PubMed2000

Conservation of polar residues as hot spots at protein interfaces.

A number of studies have addressed the question of which are the critical residues at protein-binding sites. These studies examined either a single or a few protein-protein interfaces. The most extensive study to date has been an analysis of alanine-scanning mutagenesis. However, although the total number of mutations was large, the number of protein interfaces was small, with some of the interfaces closely related. Here we show that although overall binding sites are hydrophobic, they are studded with specific, conserved polar residues at specific locations, possibly serving as energy "hot spots." Our results confirm and generalize the alanine-scanning data analysis, despite its limited size. Previously Trp, Arg, and Tyr were shown to constitute energetic hot spots. These were rationalized by their polar interactions and by their surrounding rings of hydrophobic residues. However, there was no compelling reason as to why specifically these residues were conserved. Here we show that other polar residues are similarly conserved. These conserved residues have been detected consistently in all interface families that we have examined. Our results are based on an extensive examination of residues which are in contact across protein interfaces. We utilize all clustered interface families with at least five members and with sequence similarity between the members in the range of 20-90%. There are 11 such clustered interface families, comprising a total of 97 crystal structures. Our three-dimensional superpositioning analysis of the occurrences of matched residues in each of the families identifies conserved residues at spatially similar environments. Additionally, in enzyme inhibitors, we observe that residues are more conserved at the interfaces than at other locations. On the other hand, antibody-protein interfaces have similar surface conservation as compared to their corresponding linear sequence alignment, consistent with the suggestion that evolution has optimized protein interfaces for function.

Amino Acid Sequence↗
PubMed2002

[Conservation of endangered species resources of Tibetan medicine in China].

OBJECTIVE: To further investigate and discuss the cause of species endangerment, the status and present problem of conservation of traditional Tibetan medicine in China. METHOD: Previous relevant investigations and literatures were summed up in the field. The present situation of conservation of traditional Tibetan medicine was analyzed. RESULT: The status of endangered resources, cause of species endangerment, the conserving status and conserving measures etc were elaborated. The classification was made and suggestion of species conservation of traditional Tibetan medicine were put forward. CONCLUSION: The endangered species conservation of traditional Tibetan medicine was carried out by building protective area of endangered species resources and plant garden, setting up germplasm bank, developing the domestication and cultivation of Tibetan medicinal herbs most in use, strengthening the investigation and study of endangered species, launching exchange and cooperation of conservation techniques on endangered species, enhancing the protective awareness of endangered species traditional Tibetan medicine etc. By so doing we can facilitate the sustainable development of traditional Tibetan medicine in China.

Conservation of Natural Resources↗
PubMed1994

Pilonidal sinus disease. The conservative approach.

OBJECTIVE: To examine the role of conservative, nonexcisional methods in the treatment of pilonidal sinus disease. DESIGN: Pilot nonrandomized cohort study and follow-up retrospective study. SETTING AND PATIENTS: In the pilot study, all patients treated for pilonidal sinus disease consecutively over 3 years at an Army community hospital, and in the follow-up study within a closed federal population, all patients admitted with a diagnosis of pilonidal sinus disease over 17 years to an Army medical center. INTERVENTIONS: Conservative, nonexcisional therapy (meticulous hair control by natal cleft shaving, improved perineal hygiene, and limited lateral incision and drainage for abscess) with initial comparison to excisional procedures. MAIN OUTCOME MEASURES: Occupied-bed days for conservative vs excisional therapy during a 3-year pilot study and the number of admissions and procedures performed for pilonidal sinus disease at an institution dedicated to conservative treatment alone. RESULTS: Complete healing over 83 occupied-bed days was demonstrated in 101 consecutive cases managed during 1 year with the conservative method, whereas slower healing over 4760 occupied-bed days was observed in 229 patients undergoing 240 operative procedures during the preceding 2 years. With application of conservative treatment over 17 years, only 23 excisional operations were performed. CONCLUSIONS: Conservative therapy effectively controls pilonidal sinus disease in the nonoperative outpatient setting while promoting near-normal work status and is preferred over excisional operations.

Adolescent↗
PubMed1994

Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast.

BACKGROUND: Few women with locally advanced breast cancer remain disease-free, even for 2 years. Response to induction chemotherapy may be associated with longer disease-free and overall survival rates. The role of breast conservation in selected patients with response to induction chemotherapy was evaluated. METHODS: Since 1979, patients with Stages IIB and III breast cancer have undergone induction chemotherapy; patients with response continued chemotherapy until a plateau of regression was achieved. Before 1983, all patients having a response to chemotherapy underwent mastectomy; since 1983, selected patients have undergone breast conservation. Outcomes were tallied comparing these two groups of patients. RESULTS: The study group included 189 women, who were followed up for 12-159 months (median, 46 months) after diagnosis. Of the patients, 85% had a response to induction chemotherapy. Patients with no response were excluded from additional consideration in this study. One hundred three (64%) women underwent mastectomy; 55 (36%) were treated with breast conservation. The disease-free 5-year survival rate was 61% for all patients with a response to chemotherapy; 56% for those having mastectomy and 77% for those having breast conservation. The overall 5-year survival rate was 69% for all patients with a response to chemotherapy, 67% for those undergoing mastectomy and 80% for those having breast conservation. CONCLUSIONS: Induction chemotherapy achieves significant tumor regression in most women with locally advanced breast cancer, permitting subsequent breast conservation or mastectomy with a greater expectation of long-term success. Breast conservation is used more frequently with the same expectation of success as mastectomy, presuming careful selection based on response to chemotherapy.

Adult↗
PubMed2002

Surgical versus conservative treatment for acute injuries of the lateral ligament complex of the ankle in adults.

BACKGROUND: Inversion injuries, primarily sprains, of the ankle are one of the most commonly treated injuries. The three main treatment modalities for acute lateral ankle ligament injuries are immobilisation with plaster cast or splint, 'functional treatment' comprising early mobilisation and the use of an external support (e.g. ankle brace or taping), and surgical repair or reconstruction. OBJECTIVES: We aimed to compare surgical versus conservative treatment for acute injuries of the lateral ligament complex of the ankle in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (December 2001), the Cochrane Controlled Trials Register (The Cochrane Library, Issue 4, 2001), MEDLINE (1966 to May 2000), EMBASE (1980 to May 2000), CURRENT CONTENTS (1993 to 1999), BIOSIS (to 1999), reference lists of articles, and contacted organisations and researchers in the field. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials comparing surgical with conservative interventions for treating acute injuries to the lateral ligament complex of the ankle in adults. DATA COLLECTION AND ANALYSIS: At least two, usually three, reviewers independently assessed methodological quality and extracted data. Where appropriate, results of comparable studies were pooled using fixed and random effects models and relative risks with 95% confidence intervals for dichotomous outcomes calculated. Heterogeneity between trials was tested using a standard chi-squared test. We undertook sensitivity analyses to explore the effects of inclusion of quasi-randomised trials and subgroup analyses by the two main methods of conservative treatment. MAIN RESULTS: Seventeen studies, involving a total of 1950 mostly young active adult males, were included. All trials had methodological flaws. In particular, allocation was rated as effectively concealed in only one trial and there was no report of masking outcome assessors to the interventions in any trial. Outcome measures were variously defined and data for pooling for individual outcomes were only available for a maximum of 11 studies. While there were statistically significant differences for three primary outcomes (non-return to pre-injury level of sports; undefined pain or pain on activity; and subjective or functional instability) in favour of the surgical treatment group using the fixed effects model, these findings failed to demonstrate robustness in sensitivity analyses. Exclusion of the data from explicitly quasi-randomised trials or, given the highly statistically significant heterogeneity, analyses using the random effects model modified these findings to non-statistically significant differences. There was no statistically significant difference in ankle sprain recurrence, the other primary outcome measure. Though there was a statistically significantly higher incidence of objective instability in conservatively treated patients, the functional implications of this are uncertain. There was some evidence for a lower incidence of long-term ankle swelling in surgically treated patients. However, as well as tending to take longer to resume normal activities, including work, there was some limited evidence from a few trials for a higher incidence of ankle stiffness, impaired ankle mobility and complications in the surgical treatment group. Subgroup analyses by type of conservative treatment (plaster cast or functional treatment) revealed no statistically significant differences in effect for any of the six outcomes examined. REVIEWER'S CONCLUSIONS: There is insufficient evidence available from randomised controlled trials to determine the relative effectiveness of surgical and conservative treatment for acute injuries of the lateral ligament complex of the ankle. Sufficiently powered, good quality and adequately reported randomised trials of primary surgical repair versus the best available conservative treatment for well-defined injuries are required.

Acute Disease↗
PubMed2005

Surgical versus conservative interventions for anterior cruciate ligament ruptures in adults.

BACKGROUND: Anterior cruciate ligament rupture is a common knee injury. Surgical treatment, usually involving reconstruction of the ligament, is widely used especially in active individuals. OBJECTIVES: Evaluation of the effect of surgical treatment compared with conservative treatment of anterior cruciate ligament (ACL) rupture. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to January Week 3 2005), EMBASE (1988 to 2005 Week 05), MEDIC (1978 to January 1999), Current Contents (9.2.1998 to 1.2.1999), BIOSIS (1970 to December 1998), reference lists of articles and consulted trialists and experts. SELECTION CRITERIA: All randomised and quasi-randomised trials that compared surgical with conservative treatment of ACL rupture in adults. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, data extraction and quality assessment. MAIN RESULTS: Two poor quality randomised trials conducted in the early 1980s were included in the review. The two trials differed considerably and no data pooling was done for the few shared outcome measures. One quasi-randomised trial of 167 people with a complete ACL rupture treated with repair or augmented repair versus conservative treatment found no difference in the return to sports activities between people treated surgically and those treated conservatively. Measures of knee stability and functional (Lysholm) knee scores were higher in surgically-treated participants. By the end of the follow-up period (average 55 months), three people treated with repair only and 16 treated conservatively had had ACL reconstruction. The other trial included 157 people with ACL injury. This found that conservatively-treated participants recovered from their injury more rapidly but, at the last follow up (minimum 13 months), the functional outcome was similar in both treatment groups. A large proportion of participants experienced some temporary discomfort after surgery and there were some more serious postoperative complications. There was less knee instability in surgically-treated participants and a tendency to fewer subsequent operations in the longer term. AUTHORS' CONCLUSIONS: There is insufficient evidence from randomised trials to determine whether surgery or conservative management was best for ACL injury in the 1980s, and no evidence to inform current practice. Good quality randomised trials are required to remedy this situation.

Adult↗
PubMed1995

Unstable angina: cost of conservative and invasive strategies using TIMI3 B as a model.

Obviously, conservative therapy would be less expensive than invasive therapy if patients were held in the conservative category and received only medical therapy along with exercise test with thallium. However, based on the TIMI 3 B outcomes, costs are similar (but not equal) even if one attempts a conservative strategy since a significant number of patients in the early conservative arm underwent angiography (64 patients) and PTCA (26 patients) or surgery (24 patients) and the number of days for rehospitalization was greater in the early conservative than in the early invasive group. I believe the TIMI 3 B study reflects the reality of clinical practice in 1995. It seems to me that either strategy is acceptable both from the medical and economic outcome standpoints. Given the model used here, I do not think that the early invasive strategy will ever be cheaper than the early conservative strategy unless all of the patients in the early conservative strategy who eventually are revascularized have CABG, and all of the patients in the early invasive strategy who are revascularized have PTCA.

Angina, Unstable↗
PubMed2004

Breast-conserving surgery after neoadjuvant anthracycline-based chemotherapy for large breast tumors.

BACKGROUND: Randomized trials comparing neoadjuvant versus adjuvant chemotherapy show that primary chemotherapy allows more frequent breast-preserving surgery even though no survival advantage has been demonstrated. The aim of the current study was to determine the predicting factors and the survival impact of breast conservation in patients with large breast tumors treated with neoadjuvant chemotherapy. METHODS: Between January 1987 and December 2001, 594 patients with invasive T2-3 breast carcinoma who were ineligible for breast-conserving surgery (the mean initial tumor diameter was 49 mm) were treated with 3 or 4 courses of an anthracycline-based primary chemotherapy, surgery, and radiotherapy. Various clinicopathologic factors were tested as possible predicting factors of breast-preserving surgery. Survival analyses were performed to determine the implications of breast-conserving surgery on outcome. RESULTS: After primary chemotherapy, 287 (48%) patients were eligible for breast-conserving surgery and 307 patients underwent a mastectomy. Initial tumor diameter > 5 cm, low histologic grade, lobular histology, and multicentricity were independent predicting factors of breast conservation ineligibility in the multivariate analysis (logistic regression). In the univariate survival analysis, a failure of breast-preserving surgery was associated with a poor outcome. Local disease recurrence-free survival rates were similar in patients treated with lumpectomy and mastectomy. CONCLUSIONS: The results reported in the current study suggested that initial diameter, histologic type and grade, and multicentricity are potential prechemotherapy predicting factors of breast conservation. When carefully selected, patients treated with breast conservation had a risk of local disease recurrence similar to the risk of chest wall disease recurrence after mastectomy.

Adult↗
PubMed2006

Conservative surgical approach for thyroid and lymph-node involvement in papillary thyroid carcinoma of childhood and adolescence.

BACKGROUND: Prior to 1990s, papillary thyroid carcinomas (PTCs) in childhood/adolescence underwent a standard therapeutic approach (total thyroidectomy plus elective neck dissection, followed by radioactive iodine (RAI) ablation), with an overall survival of about 100%. The aim of this study is to outline the possibility of a conservative approach (hemithyroidectomy plus selective neck dissection of clinically involved nodes, followed by TSH-suppressive therapy) in a selected group of patients. PROCEDURE: From 1968 to 2001, 42 pediatric PTC patients were treated at our institution. Absence of distant metastases and a tumor clinically limited to one lobe were both present in 28 cases that underwent a radical (20 cases) or a conservative (8 cases) surgical approach at the thyroid level. At cervical node level, 10 patients underwent a radical and 32 a conservative surgical approach. Clinicopathologic features at onset, type of therapy (radical vs. conservative), post-operative complications, and outcome till May 31, 2004 were recorded. The impact of the type of surgery on outcome was evaluated. RESULTS: Overall and progression-free survival (PFS) curves were found to be independent of the type of therapy (radical vs. conservative) in subgroups of patients matched for extent of disease at onset. Post-operative complications occurred only with radical surgical approaches. CONCLUSIONS: Childhood and adolescence PTCs show a high rate of spread but an excellent outcome independent of the type of therapy (radical vs. conservative). Taking into account the marked responsiveness to TSH-suppression and the complications after radical therapy, in selected cases, a conservative approach should be considered, reserving more aggressive therapies in case of metastases or relapse.

Adolescent↗
PubMed1995

Evolution and structural conservation of the control region of insect mitochondrial DNA.

The control regions of mitochondrial DNA of two insects, Schistocerca gregaria and Chorthippus parallelus, have been isolated and sequenced. Their sizes are 752 bp and 1,512 bp, respectively, with the presence of a tandem repeat in C. parallelus. (The sequences of the two repeats are highly conserved, having a homology of 97.5%.) Comparison of their nucleotide sequences revealed the presence of several conserved sequence blocks dispersed through the whole control region, showing a different evolutionary pattern of this region in these insects as compared to that in Drosophila. A highly conserved secondary structure, located in the 3' region near the small rRNA gene, has been identified. Sequences immediately flanking this hairpin structure rather than the sequences of this structure themselves are conserved between S. gregaria/C. parallelus and Drosophila, having a sequence consensus of "TATA" at 5' and "GAA(A)T" at 3'. The motif "G(A)nT" is also present in the 3' flanking sequences of mammalian, amphibian, and fish mitochondrial L-strand replication origins and a potential plant mitochondrial second-strand-replication origin, indicating its universal conservation and functional importance related to replication origins. The stem-and-loop structure in S. gregaria/C. parallelus appears to be closely related to that found in Drosophila despite occupying a different position, and may be potentially associated with a second-strand-replication origin. This in turn suggests that such a secondary structure might be widely conserved across invertebrates while their location in the control region may be variable. We have looked for such a conserved structure in the control regions of two other insects, G. firmus and A. mellifera, whose DNA sequences have been published, and their possible presence is discussed. Mitochondrial control regions characterized to date in five different insect taxa (Drosophila, G. firmus, A. mellifera, S. gregaria, and C. parallelus) may be classed into two distinct groups having different evolutionary patterns. It is observed that tandem repetition of regions containing a probable replication origin occurred in some species from disjunct lineages in both groups, which would be the result of convergent evolution. We also discuss the possibility of a mechanism of "parahomologous recombination by unequal crossing-over" in mitochondria, which can explain the generation of such tandemly repeated sequences (especially the first critical repetition) in the control region of mtDNA, and also their convergent evolution in disjunct biological lineages during evolution.

Animals↗
PubMed1993

Conservation and change of the developmentally crucial fushi tarazu gene in Drosophila.

We have studied the evolutionary changes occurring in the noncoding regions around the developmentally important fushi tarazu (ftz) gene in a total of 11 species in the genus Drosophila. Previous molecular developmental studies have identified DNA elements both 3' and 5' to the coding region which are important in proper regulation of expression of the Drosophila melanogaster ftz gene. We show here that these same elements are the most evolutionarily conserved regions in the vicinity of the gene homologs. Parts of some control elements are more conserved than exonic sequences. Not only is there sequence conservation, but the relative position, orientation, and distances among the control elements remain conserved. One quite significant difference does exist between the two major subgenera studied, Sophophora and Drosophila: namely, an inversion of the ftz unit with respect to other genes in the Antennapedia complex, ANT-C. As a comparison, we applied similar analysis to a "housekeeping" gene-rosy (ry), or Xdh. In contrast, DNA sequences 5' to the ry coding region revealed little evolutionary conservation. These studies bear out the proposition that functionally important DNA sequences remain more conserved through evolutionary time than do less functionally important sequences. This proposition could be tested in the present case because we could predict a priori from the developmental studies which DNA regions should be most conserved.

Animals↗
PubMed1995

Breast-conserving surgery for breast cancer: patterns of care in a geographic region and estimation of potential applicability.

BACKGROUND: It has been postulated that one of the rewards of breast cancer screening is the increased likelihood of receiving breast-conserving surgery. The recent wide application of screening mammography has led to an acceleration in the otherwise gradual shift toward smaller, earlier-stage breast cancer that has been occurring since the turn of the century. METHODS: We examined data from patients with pathologically diagnosed breast cancers from all general hospitals in the state of Vermont for use of breast-conserving surgery by era (1975-1984 [n = 1,652] versus 1989-1990 [n = 683]), method of cancer detection, age, clinical tumor-node-metastases (cTNM) stage, pathologic size, and node status. RESULTS: Cancers detected by mammography were 2% in 1975-1984 and 36% in 1989-1990. Invasive breast cancers < 2 cm maximum pathologic diameter were 34% in 1975-1984 and 50% in 1989-1990 (p < 0.001). Statewide, the use of breast-conserving surgery for invasive cancer increased from 8.6% in 1975-1984 to 42.9% in 1989-1990 (p < 0.001). In 1989-1990 at the single university hospital, 73% of the patients were treated with breast-conserving surgery versus 22% at the community hospitals (range 0-39%, p < 0.001). Differential referral patterns related to stage and age did not appear to explain the variation, because the percentages of cTNM stage I and II patients at the university hospital were similar to those of the community hospitals. Using the university hospital as the standard, we estimated that at least 67% of all patients in the state were eligible for breast-conserving surgery in the years 1975-1984 and 73% in the years 1975-1984, a 6% increase. CONCLUSIONS: Most of the variation in breast-conserving surgery was related to factors other than patient age and stage of disease. Variation was probably related more to local community factors and physician attitudes. At least two-thirds of the women in the state were eligible for breast-conserving surgery even before the wide use of mammography screening.

Adult↗
PubMed2003

Are radical and conservative substitution rates useful statistics in molecular evolution?

A DNA mutation in a protein coding gene which causes an amino acid change can be classified as "conservative" or "radical" depending on the magnitude of the physicochemical difference between the two amino acids: radical mutations involve larger changes than conservative mutations. Here, I examine two key issues in determining whether radical and conservative substitution rates are useful statistics in molecular evolution. The first issue is whether such rates can be estimated reliably, and for this purpose I demonstrate considerable improvements achieved by simple modifications to an existing method. The second issue is whether conservative and radical substitution rates can tell us something about selection on protein function. I address this problem by estimating positive and negative selection on conservative and radical mutations using polymorphism and divergence data from Drosophila. These analyses show that negative selection, but not positive selection, differs significantly between conservative and radical mutations. The power of conservative and radical substitution rates in testing the nearly neutral theory of molecular evolution is illustrated by the analysis of two mammalian datasets.

Animals↗
PubMed2000

Multiple Species Habitat Conservation Planning: Goals and Strategies of Local Governments.

Drawing from experiences gained from the development and implementation of four approved habitat conservation plans (HCPs), I describe the goals and strategies used by the nine local government members of the Riverside County Habitat Conservation Agency (RCHCA) to reconcile conflicts among a rapidly growing population and the need to conserve the habitat of a number of declining wildlife species in western Riverside County, California. Several important goals have been pursued by RCHCA member governments in their sponsorship of multiple-species habitat conservation plans (MSHCPs), including (1) establishing certainty and control over future uses of land; (2) eliminating project-by-project negotiations with federal and state wildlife agencies; (3) coordinating mitigation obligations under the Endangered Species Act, Clean Water Act, California Environmental Quality Act, and other federal and state laws; (4) reducing conflict and litigation resulting from land development activities; and (5) ensuring that wildlife conservation activities are conducted in a manner that permits local governments to perform those functions necessary to maintain public health, safety, and welfare. I also describe the emergence of strategies by local governments to achieve MSHCP goals, including (1) use of an inclusive planning process that seeks to build consensus among affected interests; (2) extensive involvement of federal and state wildlife agencies in the preparation of MSHCP documents; (3) management of public lands to support MSHCP conservation objectives; (4) encouragement of voluntary conservation by private property owners through incentive programs; and (5) active solicitation of federal and state funding for MSHCP implementation activities.

Journal Article↗
PubMed1998

ENVIRONMENTAL AUDITING: Indicators Assessment for Habitat Conservation Plan of Yolo County, California, USA.

/ Whereas habitat conservation plans (HCPs) have been intended to provide comprehensive environmental mitigation for multiple species, they often narrow in focus to one species and either one mitigation site or unspecified sites. We developed an indicators framework from which to rate land units for their ecological integrity, collateral values (nonbiological qualities that can improve conservation), and restoration and conservation opportunities. The ratings of land units were guided by the tenets of conservation biology and principles of landscape and ecosystem ecology, and they were made using existing physical and floral information managed on a GIS. As an example of how the indicators approach can be used for HCPs, the 29 legally rare species targeted by the Yolo County HCP were each associated with vegetation complexes and agricultural crops, the maps of which were used for rating some of the landscape indices. The ratings were mapped so that mitigation can be directed to the places on the landscape where the legally rare species should benefit most from conservation practices. The most highly rated land units for conservation opportunity occurred along streams and sloughs, especially where they emerged from the foothills and entered the Central Valley and where the two largest creeks intersected the Sacramento River flood basin. We recommend that priority be given to mitigation or conservation at the most highly rated land units. The indices were easy to measure and can be used with other tools to monitor the mitigation success. The indicators framework can be applied to other large-area planning efforts with some modifications.KEY WORDS: Ecosystem; Indicators; Landscape; Mitigation; Planning; Yolo County; California

Journal Article↗