Molecular diversity and genetic signatures of local adaptations in brown hares (Lepus europaeus Pallas, 1778) from heterogenous landscapes

Abstract

<p>U&nbsp; ovom&nbsp; radu&nbsp; sagledan&nbsp; je&nbsp; molekularni&nbsp; diverzitet,&nbsp; filogeografska&nbsp; struktura,<br />prostorna&nbsp; distribucija&nbsp; molekularnog&nbsp; diverziteta,&nbsp; kao&nbsp; i&nbsp; prisustvo&nbsp; selekcionih<br />signala i genetičkih signala lokalnih adaptacija kod 251 jedinke&nbsp; vrste&nbsp; Lepus<br />europaeus (Pallas,&nbsp; 1778)&nbsp; sa&nbsp; teritorije&nbsp; Evrope&nbsp; i&nbsp; Bliskog&nbsp; Istoka,&nbsp; a&nbsp; na&nbsp; osnovu<br />analize&nbsp; varijabilnosti&nbsp; sekvenci&nbsp; D&nbsp; petlje&nbsp; mtDNK, MT-ND2,&nbsp; MT-ND6,&nbsp; MHCDQA, MHC-DQB i TLR2 gena. Uočen je visok nivo parametara molekularnog<br />diverziteta&nbsp; za&nbsp; sve&nbsp; ispitivane&nbsp; molekularne&nbsp; markere.&nbsp; Utvrđeno&nbsp; je&nbsp; postojanje<br />filogeografske&nbsp; strukturiranosti&nbsp; vrste&nbsp; na&nbsp; osnovu&nbsp; mtDNK,&nbsp; kao&nbsp; i&nbsp; asimetričan<br />protok gena jedinki sa teritorije Anadolije na teritoriju Balkana&nbsp; na osnovu D<br />petlje mtDNK, MT-ND2 i MT-ND6 gena, dok je na osnovu sekvenci D petlje<br />mtDNK uočena gotovo tri puta veća stopa protoka gena sa Balkana u centralnu<br />i&nbsp; zapadnu&nbsp; Evropu.&nbsp; Utvrđeno&nbsp; je&nbsp; prisustvo&nbsp; signala&nbsp; poizivne&nbsp; selekcije&nbsp; u&nbsp; okviru<br />MT-ND6&nbsp; gena,&nbsp; kao&nbsp; i&nbsp; efekat&nbsp; klimatskih&nbsp; parametara&nbsp; (precipitacije)&nbsp; na<br />distribuciju&nbsp; proteinskih&nbsp; varijanti&nbsp; ND6C&nbsp; i&nbsp; ND6F,&nbsp; kao&nbsp; moguća&nbsp; posledica<br />regionalnih adaptacija na razlike u sredinskim uslovima. Pokazano je odsustvo<br />signala&nbsp; filogeografske&nbsp; strukturiranosti&nbsp; na&nbsp; osnovu MHC-DQA, MHC-DQB i<br />TLR2 gena.&nbsp; Uočeno&nbsp; je&nbsp; postojanje&nbsp; prostorne&nbsp; strukturiranosti&nbsp; na&nbsp; osnovu&nbsp; gena<br />imunskog&nbsp; sistema,&nbsp; i&nbsp; definisane&nbsp; su&nbsp; dve&nbsp; prostorne&nbsp; grupe,&nbsp; jedna&nbsp; koja&nbsp; je<br />obuhvatala&nbsp; jedinke&nbsp; sa&nbsp; teritorije&nbsp; Bliskog&nbsp; Istoka,&nbsp; i&nbsp; druga&nbsp; koja&nbsp; je&nbsp; obuhvatala<br />jedinke&nbsp; sa&nbsp; teritorije&nbsp; Evropi.&nbsp; Vi&scaron;e&nbsp; vrednosti&nbsp; parametara&nbsp; molekularnog<br />diverziteta uočene su u anadolijskoj grupi, u poređenju sa evropskom grupom.<br />Uočen je signal delovanja pozitivne i negativne selekcije u MHC-DQA i MHCDQB genima, kao i signal negativne selekcije u TLR2 genu. Pokazan je efekat<br />klimatskih&nbsp; parametara&nbsp; na&nbsp; distribuciju&nbsp; najzastupljenijih&nbsp; proteinskih&nbsp; varijanti<br />MHC-DQA&nbsp; i&nbsp; MHC-DQB&nbsp; gena kao&nbsp; indirektni&nbsp; pokazatelj&nbsp; imunogenetičkih<br />adaptacija&nbsp; na&nbsp; sredinski&nbsp; uslovljene&nbsp; pretpostavljene&nbsp; razlike&nbsp; u&nbsp; distribuciji<br />patogena.&nbsp; Mehanizam&nbsp; oblikovanja&nbsp; varijabilnosti&nbsp; MHC&nbsp; gena&nbsp; rezultat&nbsp; je<br />uzajamnog delovanja mutacija, rekombinacija i selekcije.</p>

<p>In&nbsp; this&nbsp; doctoral&nbsp; dissertation,&nbsp; molecular&nbsp; diversity,&nbsp; phylogeographic&nbsp; structure,<br />spatial&nbsp; distribution&nbsp; of&nbsp; molecular&nbsp; diversity,&nbsp; detection&nbsp; of&nbsp; possible&nbsp; selection<br />signals&nbsp; shaping&nbsp; the&nbsp; evolution of&nbsp; these&nbsp; genes,&nbsp; as&nbsp; well&nbsp; as&nbsp; the&nbsp; presence&nbsp; of<br />local/regional&nbsp; adaptations&nbsp; in&nbsp; correlation&nbsp; was&nbsp; examined&nbsp; in&nbsp; 251&nbsp; brown&nbsp; hares<br />from&nbsp; Europe&nbsp; and&nbsp; the&nbsp; Middle East&nbsp; based&nbsp; on&nbsp; the&nbsp; analyses&nbsp; of&nbsp; mitochondrial&nbsp; D<br />loop,&nbsp; mitochondrially&nbsp; Encoded&nbsp; NADH&nbsp; Dehydrogenase&nbsp; 2&nbsp; (MT-ND2),<br />mitochondrially&nbsp; Encoded&nbsp; NADH&nbsp; Dehydrogenase&nbsp; 6&nbsp; (MT-ND6),&nbsp; exon&nbsp; 2&nbsp; of<br />MHC Class II genes MHC-DQA,MHC-DQB and Toll Like Receptor 2 (TLR2)<br />gene sequences. A high level of molecular diversity was found based on the all<br />applied&nbsp; markers.&nbsp; Strong&nbsp; signal&nbsp; of&nbsp; phylogeographical&nbsp; and&nbsp; spatial&nbsp; structuring<br />was&nbsp; observed&nbsp; for&nbsp; mtDNA,&nbsp; most&nbsp; likely&nbsp; as&nbsp; a&nbsp; consequence&nbsp; of&nbsp; climatic<br />perturbations&nbsp; during&nbsp; the&nbsp; Pleistocene.&nbsp; The&nbsp; evolutionary&nbsp; development&nbsp; of&nbsp; hares<br />from&nbsp; Anatolia/Israel&nbsp; to&nbsp; the&nbsp; Balkans,&nbsp; and&nbsp; furthermore&nbsp; to&nbsp; central&nbsp; and&nbsp; western<br />Europe was suggested by several lines of evidences, which include dating the<br />population&nbsp; demography&nbsp; based&nbsp; on&nbsp; D-loop&nbsp; sequences,&nbsp; the&nbsp; observed&nbsp; migration<br />patterns,&nbsp; results&nbsp; of&nbsp; demographic&nbsp; tests,&nbsp; and&nbsp; apparent&nbsp; reduction&nbsp; in&nbsp; molecular<br />diversity&nbsp; indices&nbsp; along&nbsp; this&nbsp; trajectory.&nbsp; Positive&nbsp; selection&nbsp; acting&nbsp; on MT-ND6<br />gene&nbsp; was&nbsp; detected,&nbsp; together&nbsp; with&nbsp; significant&nbsp; climatic&nbsp; effect&nbsp; shaping&nbsp; the<br />distribution&nbsp; of&nbsp; the&nbsp; most&nbsp; prevalent&nbsp; protein&nbsp; variants&nbsp; found&nbsp; in&nbsp; this&nbsp; gene,<br />supposedly&nbsp; as&nbsp; a&nbsp; consequence&nbsp; to&nbsp; local/regional&nbsp; adaptations&nbsp; due&nbsp; to&nbsp; the<br />environmentally induced different energetic requirements and optimization of<br />OXPHOS&nbsp; genes.&nbsp; On&nbsp; the&nbsp; other&nbsp; side,&nbsp; less&nbsp; evident&nbsp; phylogeographic&nbsp; signal&nbsp; and<br />absence&nbsp; of&nbsp; strong&nbsp; structuring&nbsp; was&nbsp; revealed&nbsp; in&nbsp; MHC&nbsp; genes.&nbsp; High&nbsp; diversity&nbsp; at<br />MHC genes seems to be shaped by the interplay of recombination, selection<br />mechanisms&nbsp; and&nbsp; adaptations.&nbsp; Balancing&nbsp; selection&nbsp; seems&nbsp; to&nbsp; maintain&nbsp; a&nbsp; high<br />molecular&nbsp; diversity&nbsp; within&nbsp; these&nbsp; genes,&nbsp; while&nbsp; directional selection&nbsp; promotes<br />local/regional adaptations to pathogenic landscapes, as indirectly suggested by<br />a&nbsp; significant&nbsp; effect&nbsp; of&nbsp; climatic&nbsp; parameters&nbsp; on&nbsp; the&nbsp; distribution&nbsp; of&nbsp; protein<br />variants in both examined MHC genes.</p>