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17: Landscape Diversity - Biology

17: Landscape Diversity - Biology


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A landscape is "a mosaic of heterogeneous land forms, vegetation types, and land uses" (Urban et al., 1987). Therefore, assemblages of different ecosystems (the physical environments and the species that inhabit them, including humans) create landscapes on Earth. Although there is no standard definition of the size of a landscape, they are usually in the hundred or thousands of square miles.

Species composition and population viability are often affected by the structure of the landscape; for example, the size, shape, and connectivity of individual patches of ecosystems within the landscape (Noss, 1990). Conservation management should be directed at whole landscapes to ensure the survival of species that range widely across different ecosystems (e.g., jaguars, quetzals, species of plants that have widely dispersed pollen and seeds) (Hunter, 2002: 83-85, 268-270).

Diversity within and between landscapes depends on local and regional variations in environmental conditions, as well as the species supported by those environments. Landscape diversity is often incorporated into descriptions "ecoregions,"

Glossary

Landscape
a mosaic of heterogeneous land forms, vegetation types, and land uses (Urban et al., 1987)

The landscape of the A-to-I RNA editome from 462 human genomes

A-to-I editing, as a post-transcriptional modification process mediated by ADAR, plays a crucial role in many biological processes in metazoans. However, how and to what extent A-to-I editing diversifies and shapes population diversity at the RNA level are largely unknown. Here, we used 462 mRNA-sequencing samples from five populations of the Geuvadis Project and identified 16,518 A-to-I editing sites, with false detection rate of 1.03%. These sites form the landscape of the RNA editome of the human genome. By exploring RNA editing within and between populations, we revealed the geographic restriction of rare editing sites and population-specific patterns of edQTL editing sites. Moreover, we showed that RNA editing can be used to characterize the subtle but substantial diversity between different populations, especially those from different continents. Taken together, our results demonstrated that the nature and structure of populations at the RNA level are illustrated well by RNA editing, which provides insights into the process of how A-to-I editing shapes population diversity at the transcriptomic level. Our work will facilitate the understanding of the landscape of the RNA editome at the population scale and will be helpful for interpreting differences in the distribution and prevalence of disease among individuals and across populations.

Conflict of interest statement

The authors declare no competing interests.

Figures

Characterization of RNA editing sites…

Characterization of RNA editing sites in five populations. ( A ) Sequence preferences…

Landscape of the RNA editome…

Landscape of the RNA editome in human genomes. Identified RNA editing sites within…

RNA editing sites shared within…

RNA editing sites shared within and between populations. ( A ) Fraction of…

Cis- and trans-edQTLs in populations.…

Cis- and trans-edQTLs in populations. ( A ) FDR for each A-to-I editing…

Structural motifs of edQTL editing…

Structural motifs of edQTL editing sites between populations. ( A ) Heatmaps showing…


Biology scholars diversify grad-school landscape


Coming to Cornell from an Oklahoma high school with limited resources and a significant dropout rate, Emily Frech ’17 was a little intimidated sitting next to fellow Cornell freshmen biology majors, some of whom went to elite high schools catering to pre-med students.

While Frech was on top of her game academically, “I felt I didn’t quite belong here,” she said.

At the beginning of her freshman year, she applied to the Office of Undergraduate Biology’s Biology Scholars Program (BSP), which offers mentoring, study groups and guidance to biology majors from underrepresented groups.

Frech said the program helped her deal with an occasional B and C, grades she hadn’t received in high school.

“I learned that here you are a small fish in a big pond,” she said. She also learned to balance her work with other activities for her, it's the Big Red Marching Band, where she leads the drumline. And BSP connected her to faculty in her interest area of human nutrition, enabling her to join a lab freshman year.

BSP, which started in 2006, accepts about 35 freshmen each year. Of the 120 biology scholar graduates from 2010 to 2016, 91 percent of those who applied to medical school have been admitted, 19 are in Ph.D. programs and three are enrolled in M.D./Ph.D. programs.

“The success of the Biology Scholars Program stems largely from the hard work and dedication of the students themselves,” said Jeff McCaffrey, assistant director of advising in the Office of Undergraduate Biology and coordinator of the program. “BSP provides a framework within which members can improve and excel academically, contribute to the success and well-being of their peers, and become engaged in their scientific community. We also have biology faculty who volunteer each semester to share their expertise, career stories and time to help biology scholars understand the nuances of scientific research.”

The program helps tackle the lack of diversity in medical schools, graduate programs and other fields in biology. This lack of diversity affects not only the way research dollars are spent but leads to disparate care for patients, McCaffrey said.


While underrepresented minorities comprise 13 percent of the U.S. population, just 4 percent of the physician workforce and only 5.3 percent of U.S. medical school faculty are underrepresented minorities, a figure that has changed little over the past decade, according to the Association of American Medical Colleges (AAMC).

Along with racial and ethnic diversity, there’s also a lack of socioeconomic diversity among students in U.S. medical schools, with the AAMC reporting that entering medical students from the lowest income quintile have never been greater than 5.5 percent of the total of new students.

Cornell students can apply to BSP during the first semester of their freshman year. Scholars are assigned to weekly study groups and start to coalesce as a unit during an outing at the Hoffman Challenge Course. They also take two one-credit seminars freshman and sophomore year, where they talk about everything from connecting with professors to finding a research lab to exploring career options.

They also are invited to a series of special events – faculty dinners, social outings, alumni networking events, site visits to medical/graduate schools and guest speakers.

“Through BSP, I’ve developed some of my closest friends,” said Jessica Nino de Rivera ’17, a biological sciences major who wants to combine her interests in medicine and health care policy. “The program has done so much for me. As a first-generation student, I want to help others who are coming from similar backgrounds.”

Nino de Rivera has been a study group leader for general and organic chemistry courses. “I tell freshmen not to be scared, that if they put in the effort and ask questions when they need help, they will be OK,” she said.

Biology scholars quickly develop a sense of belonging at Cornell, which has a positive impact on their academic success and social adjustment.

“BSP helped me to realize the importance of working in groups,” said Daniel Veronese ’17, a biological sciences major with a concentration in ecology and evolutionary biology.

Veronese, who moved to the U.S. from Venezuela when he was 11, knew he wanted to study biology but thought his only career choices were in medicine until he was selected as one of 12 biology scholars to take part in the Galapagos curriculum. That curriculum is a set of linked courses in the spring of freshman year – an intensive version of Introductory Evolutionary Biology (sciences), a thematic freshman writing seminar (humanities) and a scientific illustration seminar (arts). The curriculum includes an expenses-paid trip to the Galapagos archipelago over spring break, led by Irby Lovette, the Fuller Professor of Ornithology and associate director for academic affairs at the Cornell Lab of Ornithology.

Veronese said that experience opened his mind to field work with animals and careers in research. The following summer, he did field work in Australia and was amazed “that I could have a career in something that I loved to do every day.”

Hendryck Gellineau ’19 also connected with research early on in his Cornell career, helping him to discover a love of chemistry (now his major).

After taking a chemistry class as a freshman and reading a story about copper and how it might be used in pharmaceuticals, Gellineau contacted Justin Wilson, a new Cornell chemistry faculty member studying metal complexes, who eventually invited Gellineau to join his lab.

“He had me doing a lot of different reactions as a freshman,’” he said, so Gellineau stayed on in the lab last summer as part of Cornell’s HHMI Accelerating Medical Progress through Scholarship program, while also taking an organic chemistry course.

Gellineau thinks he might want to get an M.D./Ph.D. focusing on organic chemistry and may get into drug development.

“I think where I can be helpful is behind the scenes,” he said, “getting doctors in the emergency rooms what they need to help patients.”


Linguistic and biological diversity linked

A lion relaxes in the Serengeti National Park, Tanzania. Credit: Larry Gorenflo, Penn State

Cultural diversity—indicated by linguistic diversity—and biodiversity are linked, and their connection may be another way to preserve both natural environments and Indigenous populations in Africa and perhaps worldwide, according to an international team of researchers.

"The punchline is, that if you are interested in conserving biological diversity, excluding the Indigenous people who likely helped create that diversity in the first place may be a really bad idea," said Larry Gorenflo, professor of landscape architecture, geography and African studies, Penn State. "Humans are part of ecosystems and I hope this study will usher in a more committed effort to engage Indigenous people in conserving localities containing key biodiversity."

Gorenflo, working with linguist Suzanne Romaine, Merton College, University of Oxford, UK, looked at 48 localities in Africa designated by the United Nations Education, Scientific and Cultural Organization (UNESCO) as Natural World Heritage Sites. These sites host "globally important natural or combined natural and cultural resources," they report. This paper was placed online as an unedited manuscript in January 2021 ahead of final online publication in April 2021 in Conservation Biology.

They analyzed geographic information system data on Indigenous languages in these areas and found that 147 languages overlapped with the UNESCO sites. Indigenous languages occurred in all but one of the Natural World Heritage Sites examined.

"The Namib Sand Sea desert in Namibia is a pretty dry area," said Gorenflo. "Kind of desolate, with wonderful sand dunes and natural features, but so harsh that there is no one living there as far as I know."

But in all the other Natural World Heritage Sites in continental Africa and on nearby islands, Indigenous people not only live, but, to some extent, manage the environment in which they live and have been doing so for a long time.

Masai boy standing in a field with a stick in the Ngorongoro Conservation Area, Tanzania. Credit: Larry Gorenflo, Penn State

"The big message is basically that there is increasing evidence that cultural diversity and biodiversity are interrelated, and we found this at a fairly fine geographic scale," said Gorenflo. "If this is the case, then it makes a strong argument for Indigenous people to be part of ecosystem management in sites where they live.

"In terms of management approach, when there is more than one linguistic group associated with a specific site, the strategy probably should be to let the people associated with individual areas deal with those areas," he said.

In addition to finding that speakers of Indigenous languages often live in high-profile UNESCO sites, the researchers also found that the number of languages in these localities correlated with the number of species whose ranges of occurrence include these sites.

For their language data, the team used Ethnologue, a linguistic database originally established to translate the bible and the only global dataset for languages with detailed geographic information.

"The database is certainly not totally correct," said Gorenflo. "But it does show major patterns."

For the species data, the researchers used the International Union for Conservation of Nature's Red List of Endangered Species which includes species range data. They looked at amphibians, mammals, reptiles and a collection of freshwater species. They also used data from Birdlife International and "Handbook of the Birds of the World" for bird species.

A small herd of zebra in the Ngorongoro Conservation Area, Tanzania. Credit: Larry Gorenflo, Penn State

"What we found numerically is that within UNESCO World Heritage Sites, if you plot language numbers against species range numbers, you find that there is a positive relationship," said Gorenflo. "It may be because more natural complexity generates more cultural complexity, though we do not know for sure."

Study results revealed that in the UNESCO sties in Africa, Indigenous languages overlapped with the ranges of more than 8,200 species in the groups considered.

Gorenflo suggests that there might be a reduction in biodiversity in these globally important African sites if Indigenous groups are displaced or somehow have their influence on managing these localities marginalized.

"Our ultimate goal is to try to look at a few places and figure out how we might redesign and reconsider management strategies and get Indigenous people more involved in shared governance."

Focusing on these high-profile UNESCO sites provides a basis for engaging Indigenous people in governance that hopefully will extend to less noteworthy places in Africa and beyond, according to Gorenflo.

He hopes to examine specific areas to increase their understanding of the relationship between biological and linguistic diversity, focusing first on the Eastern Arc Mountains of Tanzania where much of the linguistic and biological diversity occur in this nation. He also plans to examine Vanuatu, an archipelago in the eastern Melanesian Islands Biodiversity Hotspot with particularly dense linguistic diversity. Two other biodiversity hotspots of interest are Indo-Burma—Cambodia, Lao, Viet Nam, Myanmar and Southern China—and Mesoamerica, two regions where linguistic diversity is also quite high.


Avian Diversity: Speciation, Macroevolution, and Ecological Function

The origin, distribution, and function of biological diversity are fundamental themes of ecology and evolutionary biology. Research on birds has played a major role in the history and development of these ideas, yet progress was for many decades limited by a focus on patterns of current diversity, often restricted to particular clades or regions. Deeper insight is now emerging from a recent wave of integrative studies combining comprehensive phylogenetic, environmental, and functional trait data at unprecedented scales. We review these empirical advances and describe how they are reshaping our understanding of global patterns of bird diversity and the processes by which it arises, with implications for avian biogeography and functional ecology. Further expansion and integration of data sets may help to resolve longstanding debates about the evolutionary origins of biodiversity and offer a framework for understanding and predicting the response of ecosystems to environmental change.


Methods

Patient recruitment

We prospectively and consecutively recruited primary breast cancer tissue samples and matched blood samples from patients who visited two institutions (Yonsei Cancer Center and Asan Medical Center, Korea) from April 2013 to February 2019. In addition, we also searched the metastatic breast cancer database at Yonsei Cancer Center (n = 2548). The criteria for extreme responders were (1) a complete or (2) partial response for more than two times the reported progression-free survival (PFS) for metastic breast cancer in historical data. The criteria for non-responders were (1) no shrinkage in tumor diameter and (2) progressive disease as the best response. Clinical information, including age, sex, treatment duration, best response to treatment, percent change in tumor size, previous treatment history, and survival data, were collected. Tumor response evaluation was conducted as per Response Evaluation Criteria in Solid Tumor (RECIST), version 1.1 32 . The study protocol was approved by the independent ethics committee and institutional review board of Severance Hospital and was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. All patients provided written informed consent for genomic testing in this study. Specimens were evaluated by a board-certified pathologist (J.S.K.) to identify tumor-bearing areas for DNA extraction.

Genome variant analysis

Whole exome sequencing and preprocessing

Genomic DNA was isolated from formalin-fixed paraffin-embedded (FFPE) specimens using QIAamp DNA FFPE Tissue Kits (Qiagen). Genomic DNA was used for SureSelectXT Target Enrichment library generation (Agilent) and was then captured by Human All Exon V5 (Agilent). We performed whole exome sequencing analysis using Illumina HiSeq2500. For the improved quality of variant calls, we followed the Genome Analysis Toolkit (GATK) best practice of data pre-processing for variant discovery 33 . Sequencing reads for normal and tumor samples were aligned and processed to the human reference genome (UCSC hg19) using BWA-MEM v0.7.17 and Picard tools v2.19.0 (http://broadinstitute.github.io/picard/) 34 .

Single-nucleotide variants (SNVs) and indel calling

Somatic SNVs and indels were identified in normal–tumor paired samples by Mutect2 in GATK v4.1.0.0, with the min-base-quality-score option set to 30 35 . SNVs were annotated and filtered with SnpEff and SnpSift v4.1 based on dbSNP v151 36,37,38 . Also, we annotated common somatic mutations in the Catalog of Somatic Mutation in Cancer (COSMIC) database v86 39 . To minimize the calling of false-positive SNVs resulting from artifacts, such as FFPE contamination, we used the modules of GetPileupSummaries, CalculateContamination, CollectSequencingArtifactMetrics, and FilterByOrientationBias included in the GATK variant filtering.

To retain only high confidence nonsynonymous coding variants, we applied the following criteria for an additional filtration of the initial call set: (1) variants rejected by the Mutect2 filter, (2) variants included in noncoding regions, (3) variants with alternate allele counts <3, (4) variants with an allele frequency <0.1, and (5) variants with a total allele count (read depth) <20.

Copy number variants (CNVs) calling

CNVs were called using EXCAVATOR2 v1.1.2, with the option minimum mapping quality >30 40 . A paired mode was used to compare CNVs in tumor samples with matched controls. Genomics regions with an estimated copy number fraction >3 between tumor and control tissue were considered as duplications. Similarly, regions with fractions <1 were called as deletions. We considered a gene to be affected by CNVs if the entire exonic region of the gene was completely contained in the CNV calls. Genes with low coverage (average read-depth < 20) were removed to reduce false positivity. The entire process of genomic variant analysis is summarized in Supplementary Fig. 1.

Analysis of mutational burden and group specificity

One-tailed Wilcoxon rank-sum test was used to test whether mutational burden (nonsynonymous somatic mutations and CNVs) differed between the responder and non-responder groups. To test for group-specific enrichment of genomic variants, Fisher’s exact test was conducted for each called variant (nonsynonymous mutations, indels, and CNVs), applying a cut-off P value of 0.05. In Supplementary Fig. 5, we denoted genes with group-specific CNV selected by Fisher exact test in each group and genes with CNV that recurrence in both groups. The function impact of somatic SNVs was predicted using PROVEAN v1.1.5 or SIFT v6.2.1 41,42 . All statistical analyses were performed using R version 3.6 (http://www.r-project.org) with wilcox.test and fisher.test functions.

Mutation signature and enrichment pathway analysis

The relative contribution of COSMIC mutational signatures v3 was assessed within our responders and non-responders using Mutalisk with breast cancer-specific signatures based on PCAWG signature. And we performed cross-validatation using SigProfiler 43 . A matrix containing the information on the somatic mutation variants was created using the module of SigProfilerMatrixGenerator with exome option and then used for signature extraction and visualization through SigProfilerExtractor and SigProfilerPlotting. To proceed with the enrichment analysis, we selected genes that were mutated in more than two patients within each group. The selected gene list in each group was used as the input data for analyzing mutated signaling pathways in Enrchr 44 .

Inference of clonal populations and impurity

The clonal populations of each patient with respect to CNVs and allelic counts were inferred using the PyClone with the Beta Binomial emission model 45 . PyClone was performed using binomial emission densities and the pior option of total copy number for higher confidence of clonal populations. The suggested cut-offs of each feature were determined using impurity for distinguishing extreme responders from non-responder. The Gini index impurity measure is one of the split criteria of the decision tree in the Classification. The smaller the Gini index means that the better the classification, and that Gini index used for cut-off value to distinguish the two groups. The Gini index was used to measure the impurity of mutational burden, copy number burden, and clones as follows: (> = 1 - mathop olimits_^n <>>>>^2>) , where Pci is the probability of class Ci 46 .

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.


Electronic supplementary material is available online at https://dx.doi.org/10.6084/m9.figshare.c.4205108.

Published by the Royal Society. All rights reserved.

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Author information

Present address: Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA

Affiliations

National Cancer Institute RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA

Suman Mukhopadhyay & Frank McCormick

Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

Dana–Farber Cancer Institute, Boston, MA, USA

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA

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Contributions

All authors conceived of the article, performed literature searches, integrated the information and wrote, discussed and edited the manuscript.

Corresponding author


Influence of landscape context on the abundance and diversity of bees in Mediterranean olive groves

The diversity and abundance of wild bees ensures the delivery of pollination services and the maintenance of ecosystem diversity. As previous studies carried out in Central Europe and the US have shown, bee diversity and abundance is influenced by the structure and the composition of the surrounding landscape. Comparable studies have so far not been carried out in the Mediterranean region. The present study examines the influence of Mediterranean landscape context on the diversity and abundance of wild bees. To do this, we sampled bees in 13 sites in olive groves on Lesvos Island, Greece. Bees were assigned to five categories consisting of three body size groups (small, medium and large bees), the single most abundant bee species ( Lasioglossum marginatum ) and all species combined. The influence of the landscape context on bee abundance and species richness was assessed at five radii (250, 500, 750, 1000 and 1250 m) from the centre of each site. We found that the abundance within bee groups was influenced differently by different landscape parameters and land covers, whereas species richness was unaffected. Generally, smaller bees’ abundance was impacted by landscape parameters at smaller scales and larger bees at larger scales. The land cover that influenced bee abundance positively was olive grove, while phrygana, conifer forest, broad-leaved forest, cultivated land, rock, urban areas and sea had mostly negative or no impact. We stress the need for a holistic approach, including all land covers, when assessing the effects of landscape context on bee diversity and abundance in the Mediterranean.


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