Both rare and common species make unique contributions to functional diversity in an ecosystem unaffected by human activities

Aim

Rare species typically contribute more to functional diversity than common species. However, humans have altered the occupancy and abundance patterns of many species—the basis upon which we define “rarity.” Here, we use a globally unique dataset from hydrothermal vents—an untouched ecosystem—to test whether rare species over‐contribute to functional diversity.

Location

Juan de Fuca Ridge hydrothermal vent fields, Northeast Pacific Ocean.

Methods

We first conduct a comprehensive review to set up expectations for the relative contributions of rare and common species to functional diversity. We then quantify the rarity and commonness of 37 vent species with relevant trait information to assess the relationship between rarity and functional distinctiveness—a measure of the uniqueness of the traits of a species relative to traits of coexisting species. Next, we randomly assemble communities to test whether rare species over‐contribute to functional diversity in artificial assemblages ranging in species richness. Then, we test whether biotic interactions influence functional diversity contributions by comparing the observed contribution of each species to a null expectation. Finally, we identify traits driving functional distinctiveness using a distance‐based redundancy analysis.

Results

Across functional diversity metrics and species richness levels, we find that both rare and common species can contribute functional uniqueness. Some species always offer unique trait combinations, and these species host bacterial symbionts and provide habitat complexity. Moreover, we find that contributions of species to functional diversity may be influenced by biotic interactions.

Main conclusions

Our findings show that many common species make persistent, unique contributions to functional diversity. Thus, it is key to consider whether the abundance and occupancy of species have been reduced, relative to historical baselines, when interpreting the contributions of rare species to functional diversity. Our work highlights the importance of testing ecological theory in ecosystems unaffected by human activities for the conservation of biodiversity.     

The cis-Pro touch-turn: a rare motif preferred at functional sites

A new motif of three-dimensional (3D) protein structure is described, called the cis-Pro touch-turn. In this four-residue, three-peptide motif, the central peptide is cis. Residue 2, which precedes the proline, has phi, psi values either in the "prePro region" of the Ramachandran plot near -130 degrees, 75 degrees or in the Lalpha region near +60 degrees, +60 degrees. The Calpha(1)-Calpha(4) distance is 4-5 A and the two flanking peptides lie parallel to one another, making van der Waals contact rather than a hydrogen bond. Apparently, this arrangement is locally unfavorable and therefore rare, usually occurring only if needed for biological function. Of the 12 examples in a 500-protein database, cis-Pro touch-turns are found at the catalytic sites of pectate lyase, Ni-Fe hydrogenase, glucoamylase, xylanase, and opine dehydrogenase and at the primary binding sites of ribonuclease H, type I DNA polymerase, ribotoxin, and phage gene 3 protein. In each of these protein families, the touch-turns serve different roles; their functional importance is supported by conservation and mutagenesis data. In analyzing the conservation patterns of these 3D motifs, new methods for in-depth quality evaluation of the structural bioinformatic data are employed to distinguish between significant exceptions and errors     

Both helical propensity and side-chain hydrophobicity at a partially exposed site in alpha-helix contribute to the thermodynamic stability of ubiquitin

Pfam family DUF1023 consists entirely of uncharacterized proteins generated by sequencing the genomes of Actinobacteria (Bateman A., et al., Nucleic Acids Res. 2004;32 Database issue:D138-141.) Utilizing sequence similarity detection methods, we infer homology between DUF1023 and alpha/beta hydrolases. DUF1023 proteins conserve the core secondary structures in alpha/beta hydrolase fold, and share similar catalytic machinery as that of alpha/beta hydrolases. We predict DUF1023 spatial structure and deduce that they function as hydrolases utilizing catalytic Ser-His-Asp triad with the serine as a nucleophile.     

Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility

The chromosomal region 10p13 has been linked to paucibacillary leprosy in two independent studies. The MRC1 gene, encoding the human mannose receptor (MR), is located in the 10p13 region and non-synonymous SNPs in exon 7 of the gene have been suggested as leprosy susceptibility factors. We determined that G396S is the only non-synonymous exon 7-encoded polymorphism in 396 unrelated Vietnamese subjects. This SNP was genotyped in 490 simplex and 90 multiplex leprosy families comprising 704 patients (47% paucibacillary; 53% multibacillary). We observed significant under-transmission of the serine allele of the G396S polymorphism with leprosy per se (P = 0.036) and multibacillary leprosy (P = 0.034). In a sample of 384 Brazilian leprosy cases (51% paucibacillary; 49% multibacillary) and 399 healthy controls, we observed significant association of the glycine allele of the G396S polymorphism with leprosy per se (P = 0.016) and multibacillary leprosy (P = 0.023). In addition, we observed a significant association of exon 7 encoded amino acid haplotypes with leprosy per se (P = 0.012) and multibacillary leprosy (P = 0.004). Next, we tested HEK293 cells over-expressing MR constructs (293-MR) with three exon 7 haplotypes of MRC1 for their ability to bind and internalize ovalbumin and zymosan, two classical MR ligands. No difference in uptake was measured between the variants. In addition, 293-MR failed to bind and internalize viable Mycobacterium leprae and BCG. We propose that the MR–M. leprae interaction is modulated by an accessory host molecule of unknown identity.     

Identification and functional analysis of vibrio vulnificus SmcR, a novel global regulator

Recently, quorum sensing has been implicated as an important global regulator controlling the production of numerous virulence factors such as capsular polysaccharides in bacterial pathogens. The nucleotide and deduced amino acid sequences of smcR, a homolog of V. harveyi luxR identified from V. vulnificus ATCC29307, were analyzed. The amino acid sequence of SmcR from V. vulnificus was 72 to 92% similar to those of LuxR homologs from Vibrio spp. Functions of SmcR were assessed by the construction of an isogenic mutant, whose smcR gene was inactivated by allelic exchanges, and by evaluating its phenotype changes in vitro and in mice. The disruption of smcR resulted in a significant alteration in biofilm formation, in type of colony morphology, and in motility. When compared with the wild-type, the smcR mutant exhibited reduced survival under adverse conditions, such as acidic pH and hyperosmotic stress. The smcR mutant exhibited decreased cytotoxic activity toward INT 407 cells in vitro. Furthermore, the intraperitoneal LD50 of the smcR mutant was approximately 10(2) times higher than that of parental wild-type. Therefore, it appears that SmcR is a novel global regulator, controlling numerous genes contributing to the pathogenesis as well as survival of V. vulnificus.     

Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster

A restriction enzyme survey of a 110-kb region including the achaete scute complex (ASC) examined 14 polymorphic molecular markers in a sample of 56 naturally occurring chromosomes. Large insertions as a class were associated with a reduction in both sternopleural and abdominal bristle number, supporting deleterious mutation-selection equilibrium models for the maintenance of quantitative genetic variation. Two polymorphic sites were independently associated with variation in bristle number measured in two genetic backgrounds as assessed by a permutation test. A 6-bp deletion near sc alpha is associated with sternopleural bristle number variation in both sexes and a 3.4-kb insertion between sc beta and sc gamma is associated with abdominal bristle number variation in females. Under an additive genetic model, the small deletion polymorphism near sc alpha accounts for 25% of the total X chromosome genetic variation in sternopleural bristle number, and the 3.4 kb insertion accounts for 22% of the total X chromosome variation in female abdominal bristle number. The observation of common polymorphisms associated with variation in bristle number is more parsimoniously explained by models that incorporate balancing selection or assume variants affecting bristle number are neutral, than mutation-selection equilibrium models.     

Contribution of rare and common species to richness patterns at local scales

Several studies have recently reported that common species are more important for species richness patterns than rare species. However, most such studies have been based on broad‐scale atlas data. We studied the contribution of different species occupancy, i.e. number of plots occupied, to species richness patterns emerging from species data in 50 by 50 m plots within six 140–200 ha forests in Norway. The study included vascular plants, lichens, bryophytes, and polypore fungi. We addressed the following questions: 1) are common species more correlated with species richness than rare species? 2) How do occupancy classes combine at various levels of species richness? 3) Which occupancy class is best in identifying the overall most species‐rich sites (hotspots) by sampling? The results showed that rare species were better correlated with species richness than common species when the information content was accounted for, that high species richness was associated with a higher proportion of less frequent species, and that the best occupancy class for local hotspot identification was species present in 10–30% of the plots within a forest. We argue that the observed correlations between overall richness and sub‐assembly richness are primarily structured by the combination of the distributions of species richness and species occupancy. Although these distributions result from general ecological processes, they may also be strongly affected by idiosyncratic elements of the individual datasets caused by the specific environmental composition of a study area. Hence, different datasets collected in different areas may lead to different results regarding the relative importance of common versus rare species, and such effects should be expected on both broad and fine spatial scales. Despite these effects, we suggest that infrequent species will tend to be more strongly correlated to species richness at local scales than at broader scales as a result of more right‐skewed species‐occupancy distributions.     

On the association of common and rare genetic variation influencing body mass index: a combined SNP and CNV analysis

Background

As the architecture of complex traits incorporates a widening spectrum of genetic variation, analyses integrating common and rare variation are needed. Body mass index (BMI) represents a model trait, since common variation shows robust association but accounts for a fraction of the heritability. A combined analysis of single nucleotide polymorphisms (SNP) and copy number variation (CNV) was performed using 1850 European and 498 African-Americans from the Study of Addiction: Genetics and Environment. Genetic risk sum scores (GRSS) were constructed using 32 BMI-validated SNPs and aggregate-risk methods were compared: count versus weighted and proxy versus imputation.

Results

The weighted SNP-GRSS constructed from imputed probabilities of risk alleles performed best and was highly associated with BMI (p = 4.3×10⁻¹⁶) accounting for 3% of the phenotypic variance. In addition to BMI-validated SNPs, common and rare BMI/obesity-associated CNVs were identified from the literature. Of the 84 CNVs previously reported, only 21-kilobase deletions on 16p12.3 showed evidence for association with BMI (p = 0.003, frequency = 16.9%), with two CNVs nominally associated with class II obesity, 1p36.1 duplications (OR = 3.1, p = 0.009, frequency 1.2%) and 5q13.2 deletions (OR = 1.5, p = 0.048, frequency 7.7%). All other CNVs, individually and in aggregate, were not associated with BMI or obesity. The combined model, including covariates, SNP-GRSS, and 16p12.3 deletion accounted for 11.5% of phenotypic variance in BMI (3.2% from genetic effects). Models significantly predicted obesity classification with maximum discriminative ability for morbid-obesity (p = 3.15×10⁻¹⁸).

Conclusion

Results show that incorporating validated effect sizes and allelic probabilities improve prediction algorithms. Although rare-CNVs did not account for significant phenotypic variation, results provide a framework for integrated analyses.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-368) contains supplementary material, which is available to authorized users.     

Molecular and functional characterization of common polymorphisms in HERG (KCNH2) potassium channels

Long QT syndrome (LQTS) is a cardiac repolarization disorder that can lead to arrhythmias and sudden death. Chromosome 7-linked inherited LQTS (LQT2) is caused by mutations in human ether-a-go-go-related gene (HERG; KCNH2), whereas drug-induced LQTS is caused primarily by HERG channel block. Many common polymorphisms are functionally silent and have been traditionally regarded as benign and without physiological consequence. However, the identification of common nonsynonymous single nucleotide polymorphisms (nSNPs; i.e., amino-acid coding variants) with functional phenotypes in the SCN5A Na(+) channel and MiRP1 K(+) channel beta-subunit have challenged this viewpoint. In this report, we test the hypothesis that common missense HERG polymorphisms alter channel physiology. Comprehensive mutational analysis of HERG was performed on genomic DNA derived from a population-based cohort of sudden infant death syndrome and two reference allele cohorts derived from 100 African American and 100 Caucasian individuals. Amino acid-encoding variants were considered common polymorphisms if they were present in at least two of the three study cohorts with an allelic frequency >0.5%. Four nSNPs were identified: K897T, P967L, R1047L, and Q1068R. Wild-type (WT) and polymorphic channels were heterologously expressed in human embryonic kidney cells, and biochemical and voltage-clamp techniques were used to characterize their functional properties. All channel types were processed similarly, but several electrophysiological differences were identified: 1) K897T current density was lower than the other polymorphic channels; 2) K897T channels activated at more negative potentials than WT and R1047L; 3) K897T and Q1068R channels inactivated and recovered from inactivation faster than WT, P967L, and R1047L channels; and 4) K897T channels showed subtle differences compared with WT channels when stimulated with an action potential waveform. In contrast to K897T and Q1068R channels, P967L and R1047L channels were electrophysiologically indistinguishable from WT channels. All HERG channels had similar sensitivity to block by cisapride. Therefore, some HERG polymorphic channels are electrophysiologically different from WT channels.     

A genome-wide comparison of the functional properties of rare and common genetic variants in humans

One of the longest running debates in evolutionary biology concerns the kind of genetic variation that is primarily responsible for phenotypic variation in species. Here, we address this question for humans specifically from the perspective of population allele frequency of variants across the complete genome, including both coding and noncoding regions. We establish simple criteria to assess the likelihood that variants are functional based on their genomic locations and then use whole-genome sequence data from 29 subjects of European origin to assess the relationship between the functional properties of variants and their population allele frequencies. We find that for all criteria used to assess the likelihood that a variant is functional, the rarer variants are significantly more likely to be functional than the more common variants. Strikingly, these patterns disappear when we focus on only those variants in which the major alleles are derived. These analyses indicate that the majority of the genetic variation in terms of phenotypic consequence may result from a mutation-selection balance, as opposed to balancing selection, and have direct relevance to the study of human disease.     

The role of common and rare MC4R variants and FTO polymorphisms in extreme form of obesity

Melanocortin 4 receptor (MC4R) is an important regulator of food intake and number of studies report genetic variations influencing the risk of obesity. Here we explored the role of common genetic variation from MC4R locus comparing with SNPs from gene FTO locus, as well as the frequency and functionality of rare MC4R mutations in cohort of 380 severely obese individuals (BMI > 39 kg/m²) and 380 lean subjects from the Genome Database of Latvian Population (LGDB). We found correlation for two SNPs—rs11642015 and rs62048402 in the fat mass and obesity-associated protein (FTO) with obesity but no association was detected for rs17782313 located in the MC4R locus in these severely obese individuals. We sequenced the whole gene MC4R coding region in all study subjects and found five previously known heterozygous non-synonymous substitutions V103I, I121T, S127L, V166I and I251L. Expression in mammalian cells showed that the S127L, V166I and double V103I/S127L mutant receptors had significantly decreased quantity at the cell surface compared to the wild type MC4R. We carried out detailed functional analysis of V166I that demonstrated that, despite low abundance in plasma membrane, the V166I variant has lower EC₅₀ value upon αMSH activation than the wild type receptor, while the level of AGRP inhibition was decreased, implying that V166I cause hyperactive satiety signalling. Overall, this study suggest that S127L may be the most frequent functional MC4R mutation leading to the severe obesity in general population and provides new insight into the functionality of population based variants of the MC4R.     

Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements

The olfactory receptor (OR)-gene superfamily is the largest in the mammalian genome. Several of the human OR genes appear in clusters with > or = 10 members located on almost all human chromosomes, and some chromosomes contain more than one cluster. We demonstrate, by experimental and in silico data, that unequal crossovers between two OR gene clusters in 8p are responsible for the formation of three recurrent chromosome macrorearrangements and a submicroscopic inversion polymorphism. The first two macrorearrangements are the inverted duplication of 8p, inv dup(8p), which is associated with a distinct phenotype, and a supernumerary marker chromosome, +der(8)(8p23.1pter), which is also a recurrent rearrangement and is associated with minor anomalies. We demonstrate that it is the reciprocal of the inv dup(8p). The third macrorearrangment is a recurrent 8p23 interstitial deletion associated with heart defect. Since inv dup(8p)s originate consistently in maternal meiosis, we investigated the maternal chromosomes 8 in eight mothers of subjects with inv dup(8p) and in the mother of one subject with +der(8), by means of probes included between the two 8p-OR gene clusters. All the mothers were heterozygous for an 8p submicroscopic inversion that was delimited by the 8p-OR gene clusters and was present, in heterozygous state, in 26% of a population of European descent. Thus, inversion heterozygosity may cause susceptibility to unequal recombination, leading to the formation of the inv dup(8p) or to its reciprocal product, the +der(8p). After the Yp inversion polymorphism, which is the preferential background for the PRKX/PRKY translocation in XX males and XY females, the OR-8p inversion is the second genomic polymorphism that confers susceptibility to the formation of common chromosome rearrangements. Accordingly, it may be possible to develop a profile of the individual risk of having progeny with chromosome rearrangements.     

Drainage-structuring of ancestral variation and a common functional pathway shape limited genomic convergence in natural high- and low-predation guppies

Studies of convergence in wild populations have been instrumental in understanding adaptation by providing strong evidence for natural selection. At the genetic level, we are beginning to appreciate that the re-use of the same genes in adaptation occurs through different mechanisms and can be constrained by underlying trait architectures and demographic characteristics of natural populations. Here, we explore these processes in naturally adapted high- (HP) and low-predation (LP) populations of the Trinidadian guppy, Poecilia reticulata. As a model for phenotypic change this system provided some of the earliest evidence of rapid and repeatable evolution in vertebrates; the genetic basis of which has yet to be studied at the whole-genome level. We collected whole-genome sequencing data from ten populations (176 individuals) representing five independent HP-LP river pairs across the three main drainages in Northern Trinidad. We evaluate population structure, uncovering several LP bottlenecks and variable between-river introgression that can lead to constraints on the sharing of adaptive variation between populations. Consequently, we found limited selection on common genes or loci across all drainages. Using a pathway type analysis, however, we find evidence of repeated selection on different genes involved in cadherin signaling. Finally, we found a large repeatedly selected haplotype on chromosome 20 in three rivers from the same drainage. Taken together, despite limited sharing of adaptive variation among rivers, we found evidence of convergent evolution associated with HP-LP environments in pathways across divergent drainages and at a previously unreported candidate haplotype within a drainage.