Loss and Gain of Function in SERPINB11: An Example of a Gene under Selection on Standing Variation, with Implications for Host-Pathogen Interactions

Serine protease inhibitors (SERPINs) are crucial in the regulation of diverse biological processes including inflammation and immune response. SERPINB11, located in the 18q21 gene cluster, is a polymorphic gene/pseudogene coding for a non-inhibitory SERPIN. In a genome-wide scan for recent selection, SERPINB11 was identified as a potential candidate gene for adaptive evolution in Yoruba. The present study sought a better understanding of the evolutionary history of SERPINB11, with special focus on evaluating its selective signature. Through the resequencing of coding and noncoding regions of SERPINB11 in 20 Yorubans and analyzing primate orthologous sequences, we identified a full-length SERPINB11 variant encoding a non-inhibitory SERPIN as the putative candidate of selection – probably driven to higher frequencies by an adaptive response using preexisting variation. In addition, we detected contrasting evolutionary features of SERPINB11 in primates: While primate phylogeny as a whole is under purifying selection, the human lineage shows evidence of positive selection in a few codons, all associated with the active SERPINB11. Comparative modeling studies suggest that positively selected codons reduce SERPINB11's ability to undergo the conformational changes typical of inhibitory SERPINs – suggesting that it is evolving towards a new non-inhibitory function in humans. Significant correlations between SERPINB11 variants and the environmental variables, pastoralism and pathogen richness, have led us to propose a selective advantage through host-pathogen interactions, possibly linked to an adaptive response combating the emergence of infectious diseases in recent human evolution. This work represents the first description of a resurrected gene in humans, and may well exemplify selection on standing variation triggered by drastic ecological shifts

Educação popular e agroecologia: contribuições para a construção da política de assistência técnica e extensão rural equitativa no Brasil

This article presents reflections on the contributions of Popular Education and Agroecology to the reframing of the theoretical and methodological bases of the public policy of Technical Assistance and Rural Extension. The text highlights how the confluences between popular education and agroecology and the implications of these contributions with feminist epistemology have contributed to the equity debate in the context of public ATER. The work was structured based on a review on the theme and more specifically on the selection and review of 06 articles from the CAPES journals portal, published between 2012 and 2017. The analyzed documents discuss the ideological and epistemological bases of PNATER and the National Policy on Agroecology and Organic Production - PNAPO. The article points out some central elements in the process of reframing the diffusionist ATER towards an equitable ATER, such as the prediction of social equity, the enhancement of citizenship, the promotion of sustainable rural development based on the principles of agroecology, democratic, participatory pedagogical approaches, based on recognition the plurality and diversity of the multiple categories that make up family farming.Este artigo apresenta reflexões sobre as contribuições da Educação Popular e da Agroecologia para a ressignificação das bases teóricas e metodológicas da política pública de Assistência Técnica e Extensão Rural. O texto destaca como as confluências entre educação popular e agroecologia e as imbricações desses aportes com a epistemologia feminista vêm contribuindo para o debate de equidade no contexto da ATER pública. O trabalho foi estruturado a partir de uma revisão sobre o tema e mais especificamente da seleção e revisão de 06 artigos do portal de periódicos da CAPES, publicados entre 2012 e 2017. Os documentos analisados discutem sobre as bases ideológicas e epistemológicas da PNATER e Política nacional de Agroecologia e Produção Orgânica - PNAPO. O artigo aponta alguns elementos centrais no processo de ressignificação da ATER difusionista para uma ATER equitativa, como a previsão da equidade social, valorização da cidadania, promoção do desenvolvimento rural sustentável com base nos princípios da agroecologia, enfoques pedagógicos democráticos, participativos, pautados no reconhecimento da pluralidade e diversidade das múltiplas categorias que compõem a agricultura familiar

Inventário florestal com tecnologia laser aerotransportada de plantios de Eucalyptus spp no BrasilForest inventory with airborne laser technology of Eucalyptus spp plantations in Brazil

O presente artigo faz uma breve apresentação e análise da informação gerada pela tecnologia laser aerotransportada LIDAR em um levantamento das características altimétricas em plantios clonais de Eucalyptus no Sul da Bahia, Brasil. Uma revisão dos princípios da tecnologia LIDAR é seguida de uma descrição dos dados gerados para um subconjunto de parcelas amostrais sobrevoadas em Setembro de 2008. Os resultados do levantamento LIDAR são apresentados conjuntamente com os dados de medições convencionais de inventário florestal realizadas no campo. Considerando-se a alta precisão observada para os parâmetros diretamente relacionados com a altura das árvores, e o potencial de redução significativa da intensidade amostral de campo, barateando assim o custo final das atividades de inventário florestal, justifica-se o uso dessa tecnologia aerotransportada. Assim, será possível reduzir os extenuantes e, por vezes, imprecisos e ineficientes procedimentos de campo usados em levantamentos de extensas áreas florestadas. AbstractThis paper briefly presents and evaluates the information produced by the LIDAR airborne laser technology used to assess altimetric characteristics in cloned plantations of Eucalyptus in Southern Bahia, Brazil. A revision of the main principles of the LIDAR technology is followed by the description of data generated for a sub set of sample plots assessed in September 2008. The LIDAR assessment results are jointly presented with forest inventory data produced by conventional field measurements. Considering the observed high accuracy of the parameter directly related to tree height, and the significant potential of reduction of intensity in sample field, lowering forest inventory total costs, the use of the airborne technology is justifiable. Therefore, it will be possible to reduce the tiresome, and many times imprecise and inefficient, field procedures used to assess in extensive forest areas.

Phylogenetic-based test of selection for <i>SERPINB11</i>.

a<p>Model assuming a single ω value for all lineages in the phylogeny;</p>b<p>Model assuming diferent ω values for each lineage in the phylogeny – value obtained for the human lineage;</p>c<p>Model assuming a different ω value in <i>foreground</i> branch (in this case human lineage);</p>d<p>Sites Classes: 0 – sites under constrains; 1 – neutral sites; 2a – constrained sites under positive selection in the <i>foreground</i> branch; 2b – neutral sites under positive selection in the <i>foreground</i> branch. NS – non-significant; NA – not applicable.</p

Summary Statistics of Population Variation.

a<p>N – number of chromosomes.</p>b<p>L – total number of sites surveyed.</p>c<p>S – number of segregating sites.</p>d<p>π – Nucleotide diversity per base pair (×10⁴).</p>e<p>θ_W – Population mutation rate parameter: Watterson's estimator of θ (4Neμ) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Watterson1" target="_blank">[94]</a> per base pair (×10⁴).</p>f<p>D – Tajima's D statistic <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Tajima1" target="_blank">[21]</a>.</p>g<p>ρ – Population recombination rate parameter: Hudson's estimator of ρ (4N_er) per base pair (×10⁴), based on a conversion-to-crossover ratio of 2 and a mean conversion tract length of 500 bp <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Frisse1" target="_blank">[23]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Hudson2" target="_blank">[95]</a>.</p

<i>SERPINB11</i> genealogies as estimated by GENETREE.

<p>Time is scaled in millions of years (MY). The indicated tree branches correspond to functional variants. Solid circles represent nucleotide substitutions. The numbers below the trees represent the numbers of each haplotype. In Region I, a Ne = 6,400 was calculated and 3 incompatible sites and 2 haplotypes were removed from the analysis; in Region II, a Ne = 14,800 was calculated and 5 incompatible haplotypes were removed.</p

Worldwide distribution of common <i>SERPINB11</i> haplotypes as inferred by PHASE2 for the HGDP data [<b>35</b>].

<p>Worldwide distribution of common <i>SERPINB11</i> haplotypes as inferred by PHASE2 for the HGDP data <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Li1" target="_blank">[<b>35</b>]</a>.</p

SNP association with pathogen richness.

<p>*Haplotype E90-T181-P303.</p><p>•Blood Group Antigen genes significantly associated with pathogen richness <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Fumagalli1" target="_blank">[33]</a>. <b><i><u>ABO</u></i></b>: ABO blood group; <b><i><u>AQP3</u></i></b>: Aquaporin 3; <b><i><u>CD44</u></i></b>: CD44 antigen; <b><i><u>CD55</u></i></b>: CD55 antigen; <b><i><u>CIGALT1</u></i></b>: Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1; <b><i><u>ERMAP</u></i></b>: Erythroblast membrane-associated protein; <b><i><u>FUT2</u></i></b>: Fucosyltransferase 2; <b><i><u>GCNT2</u></i></b>: glucosaminyl (N-acetyl) transferase 2, I-branching enzyme; <b><i><u>GYPC</u></i></b>: Glycophorin C; <b><i><u>SLC4A1</u></i></b>: Solute carrier family 4, anion exchanger, member 1; <b><i><u>SLC14A1</u></i></b>: Solute carrier family 14, member 1.</p

Comparative modeling structures of the SERPINB11c sequence.

<p>The two main conformational stages of the protein are presented – Stressed (S) and Relaxed (R). The image indicates the most important regions for inhibitory function – RCL, breach, shutter, and gate <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Stein1" target="_blank">[3]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-Irving1" target="_blank">[4]</a>. Positive selection sites are highlighted and nearby elements of the secondary structure are indicated – α helix (hD and hF) and β strand (s2A, s3A, s5A, and s6A). This figure was generated using PyMOL <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032518#pone.0032518-DeLano1" target="_blank">[93]</a> (PyMOL. DeLano Scientific, San Carlos).</p