郝艷，雷富民,2,3

郝艷，2014—2020年就讀于中國科學(xué)院動(dòng)物研究所，在鳥類學(xué)研究組攻讀博士學(xué)位，導(dǎo)師是雷富民研究員。目前在中國科學(xué)院動(dòng)物研究所接受博士后訓(xùn)練，主要研究方向?yàn)轼B類對(duì)極端環(huán)境適應(yīng)的分子機(jī)制。博士期間，在不同的鳥類演化體系中，采用比較基因組學(xué)、比較轉(zhuǎn)錄組學(xué)等研究方法，結(jié)合形態(tài)學(xué)等表型數(shù)據(jù)及功能實(shí)驗(yàn)驗(yàn)證，從位點(diǎn)、基因、基因家族、生物功能通路、基因表達(dá)等角度檢測(cè)了鳥類對(duì)青藏高原極端環(huán)境適應(yīng)的趨同和趨異信號(hào)，并探討了鳥類適應(yīng)演化的可能機(jī)制。已獲得中國博士后科學(xué)基金一等面上資助項(xiàng)目、中國科學(xué)院特別研究助理資助項(xiàng)目、國家自然科學(xué)基金委青年科學(xué)基金項(xiàng)目及第七屆中國科協(xié)青年人才托舉工程項(xiàng)目。博士論文《三對(duì)近緣高低海拔雀形目鳥類的比較轉(zhuǎn)錄組學(xué)研究》獲得2021年中國科學(xué)院優(yōu)秀博士生論文。

適應(yīng)性演化的分子遺傳機(jī)制：以高海拔適應(yīng)為例

郝艷1，雷富民1,2,3

1. 中國科學(xué)院動(dòng)物研究所動(dòng)物進(jìn)化與系統(tǒng)學(xué)重點(diǎn)實(shí)驗(yàn)室，北京 100101 2. 中國科學(xué)院大學(xué)生命科學(xué)學(xué)院，北京 100049 3. 中國科學(xué)院動(dòng)物進(jìn)化與遺傳前沿交叉卓越創(chuàng)新中心，昆明 650223

自達(dá)爾文時(shí)代起，解析適應(yīng)性演化的機(jī)制一直是進(jìn)化生物學(xué)和生態(tài)學(xué)領(lǐng)域研究最重要的科學(xué)問題之一。適應(yīng)性演化通常指在自然選擇驅(qū)動(dòng)下，物種為提高適合度而演化出特定的表型。表型的適應(yīng)表現(xiàn)在形態(tài)、生理生化、組織學(xué)、行為學(xué)等多個(gè)層級(jí)。隨著分子生物學(xué)和測(cè)序技術(shù)的發(fā)展，越來越多的研究揭示了適應(yīng)性復(fù)雜性狀的遺傳基礎(chǔ)。研究適應(yīng)性演化的分子遺傳機(jī)制有助于理解塑造生物多樣性的進(jìn)化驅(qū)動(dòng)力以及闡明基因型、表型和環(huán)境之間的關(guān)聯(lián)關(guān)系。目前已有主效基因、超基因、多基因遺傳、非編碼區(qū)調(diào)控、重復(fù)序列調(diào)控、基因漸滲等多種假說可以解釋適應(yīng)性演化的遺傳機(jī)制。高海拔極端環(huán)境的強(qiáng)選擇壓力極大地促進(jìn)了物種表型和遺傳適應(yīng)的發(fā)生，對(duì)多組學(xué)數(shù)據(jù)的剖析為物種適應(yīng)性演化提供了新的見解。本文對(duì)適應(yīng)性演化的遺傳機(jī)制、高海拔極端環(huán)境適應(yīng)研究進(jìn)展以及目前面臨的主要挑戰(zhàn)進(jìn)行了綜述，并對(duì)未來的發(fā)展趨勢(shì)進(jìn)行了展望，以期為該領(lǐng)域的科研人員提供參考。

表型；非編碼區(qū)；多組學(xué)；調(diào)控；高海拔

適應(yīng)性演化是指物種在某種特定環(huán)境的選擇壓力下，演化出有利于提高其適合度的適應(yīng)性表型[1]。不同物種不同方向的適應(yīng)性演化塑造了豐富的生物多樣性，因此長期以來備受科學(xué)界關(guān)注。早在1859年，達(dá)爾文就已經(jīng)在其經(jīng)典論著《物種起源》中提出在自然選擇的作用下，物種會(huì)發(fā)生特定的改變，以適應(yīng)環(huán)境選擇壓力[2]。孟德爾學(xué)派“遺傳學(xué)之父”摩爾根提出“突變–選擇”理論，認(rèn)為演化是在不斷的突變與選擇中發(fā)生的[3]。新達(dá)爾文主義則認(rèn)為突變僅是演化的原材料，自然選擇在其中發(fā)揮了重要的作用[4]。而隨著1968年日本學(xué)者木村資生“中性學(xué)說”的提出[5]，將自然選擇理論與中性理論的爭論推上了高潮。早期分子數(shù)據(jù)中觀察到的氨基酸的改變實(shí)際上多為中性或近中性的，只有少數(shù)重要的氨基酸替代才能引起蛋白質(zhì)功能的變化，繼而促進(jìn)了表型適應(yīng)演化[6]?；谶@些理論框架，適應(yīng)性演化領(lǐng)域的研究在不斷地發(fā)展和完善。

早期針對(duì)適應(yīng)性演化的研究多集中于形態(tài)、生理生化、組織學(xué)、行為學(xué)等方面，而隨著分子生物學(xué)的發(fā)展，適應(yīng)性演化研究逐步轉(zhuǎn)向更深層次——對(duì)分子遺傳機(jī)制的探索。尤其是第二代、第三代測(cè)序技術(shù)的進(jìn)步，測(cè)序成本下降，以及大量基因組序列的公布[7～10]，極大地推動(dòng)了基因組學(xué)分析方法在野生類群適應(yīng)性演化遺傳機(jī)制研究中的廣泛應(yīng)用。同時(shí)群體基因組、轉(zhuǎn)錄組、蛋白質(zhì)組、代謝組、微生物組等多組學(xué)研究的涌現(xiàn)，為解析適應(yīng)性演化的機(jī)制帶來新的契機(jī)和研究范式。確定與適應(yīng)相關(guān)的關(guān)鍵基因和分子機(jī)制有助于明確“遺傳變異—表型變化—環(huán)境選擇”之間的關(guān)系，對(duì)于理解何種進(jìn)化力塑造了生物多樣性具有重要的意義。本文主要綜述了目前適應(yīng)性演化的分子遺傳機(jī)制和假說，并以物種對(duì)高海拔極端環(huán)境適應(yīng)為例，簡要介紹了具體的適應(yīng)機(jī)制和研究進(jìn)展。

1 適應(yīng)性演化的分子遺傳機(jī)制

1.1 主效基因假說(major-effect gene hypothesis)

主效基因假說是指單個(gè)基因甚至是單個(gè)位點(diǎn)或少數(shù)基因的變異控制適應(yīng)性表型的產(chǎn)生(圖1A)[11]。早期的進(jìn)化論支持者認(rèn)為適應(yīng)性演化的遺傳基礎(chǔ)是微小的突變，這一觀點(diǎn)在1930年Ronald A. Fisher的經(jīng)典數(shù)學(xué)分析中得到支持。但隨著20世紀(jì)80年代數(shù)量性狀和微生物實(shí)驗(yàn)進(jìn)化學(xué)科的發(fā)展，科研人員發(fā)現(xiàn)基因組中存在少數(shù)對(duì)適應(yīng)性演化起關(guān)鍵作用的基因[12]。當(dāng)物種受到強(qiáng)烈的正選擇作用時(shí)，可能會(huì)導(dǎo)致少數(shù)具有重要作用(large effects)的基因受到選擇清除(selective sweep)的影響快速固定下來，從而達(dá)到表型適應(yīng)[13]。通常這種主效基因的突變會(huì)使演化更容易且更迅速地發(fā)生[14]。

其中最經(jīng)典的是寫入教科書的實(shí)例——工業(yè)黑化的樺尺蛾()，它在極短時(shí)間內(nèi)由野生型(淺色型)演化出適應(yīng)環(huán)境污染的黑色型。Van’t Hof等[11]發(fā)現(xiàn)黑色型中存在一段核心序列有強(qiáng)烈的選擇特征。有趣的是，這段區(qū)域與其他鱗翅目控制翅型的主要基因座重疊，暗示了該區(qū)域具有重要的顏色調(diào)控遺傳基礎(chǔ)[11,15]。袖蝶屬蝴蝶()基因組中存在多樣化熱點(diǎn)的小部分基因座，相比基因組的其他區(qū)域更有可能參與和促進(jìn)蝴蝶復(fù)雜翅型的趨同和趨異演化[15]。Cooke等[16]整合全基因組關(guān)聯(lián)分析(genome-wide association studies，GWAS)和基因表達(dá)分析，發(fā)現(xiàn)虎皮鸚鵡()中編碼聚酮合酶的基因中發(fā)生了一個(gè)核苷酸多態(tài)性(single-nucleotide polymorphisms, SNPs)位點(diǎn)的非同義替代，造成了氨基酸變異(R644W)，并進(jìn)一步利用酵母體系異源表達(dá)和質(zhì)譜分析，證明了基因這一氨基酸的替代影響了聚酮合酶的活性，導(dǎo)致了野生型中的黃色色素沉積失敗，從而產(chǎn)生了藍(lán)色的羽毛。

除了著色的適應(yīng)，鳥類喙型的特化和生態(tài)適應(yīng)也被證明會(huì)受到主效基因的影響。達(dá)爾文雀(Darwin’s finches,)是通過自然選擇作用發(fā)生適應(yīng)性演化的另一典型案例。Grant夫婦針對(duì)分布于加拉帕戈斯群島和科科斯島的達(dá)爾文雀開展了長達(dá)幾十年的研究，揭示了物種如何以及為什么發(fā)生了快速多樣化[17]。其中鳥類喙型通常被認(rèn)為是代表著對(duì)特殊生態(tài)位適應(yīng)的一種重要表型[17,18]。Abzhanov等[19]使用包含6個(gè)達(dá)爾文雀的單系系統(tǒng)(monophyletic system)通過不同胚胎發(fā)育階段的樣品的原位雜交實(shí)驗(yàn)，證實(shí)了在上喙間質(zhì)中的表達(dá)與喙型深度和寬度的形狀變異密切相關(guān)。Lamichhaney等[20]通過對(duì)14種達(dá)爾文雀和2種近緣外群共120個(gè)個(gè)體進(jìn)行群體基因組學(xué)比較，發(fā)現(xiàn)了一個(gè)長度為240 kb編碼影響顱面發(fā)育的轉(zhuǎn)錄因子基因的單倍型，證明了該單倍型有助于達(dá)爾文雀喙型的多樣化，從而擴(kuò)大了該類群對(duì)食物資源的利用。最近，Cheng等[21]對(duì)青藏高原(Qinghai–Tibet Plateau, QTP)特有物種——地山雀()及其近緣的13種山雀科(Paridae)鳥類的群體基因組學(xué)進(jìn)行比較分析，發(fā)現(xiàn)具有獨(dú)特取食方式(地面取食)的地山雀相比其他物種在基因中發(fā)生了選擇清除，上出現(xiàn)的兩個(gè)非同義替代(R1493Q和P1501L)可能解釋了地山雀喙長的變異，因而使其可以適應(yīng)青藏高原開闊的生境。

1.2 超基因假說(supergene hypothesis)

超基因假說是指適應(yīng)性表型受一個(gè)包含許多緊密排列的基因座的大段區(qū)域控制(圖1B)。通常由于倒位作用，在平衡選擇作用下，該區(qū)域重組水平被顯著降低而促使基因共進(jìn)化，并連鎖發(fā)揮效應(yīng)，以調(diào)控復(fù)雜多態(tài)性狀[22～25]。性染色體被認(rèn)為是超基因的一個(gè)特殊實(shí)例[24]，由于重組抑制，除可以重組的假常染色體區(qū)(pseudoautosomal regions, PARs)外，不同物種Y或W染色體的非重組區(qū)逐步形成復(fù)雜的“進(jìn)化層”(evolutionary strata)模式[26,27]。最近的一系列研究表明超基因在適應(yīng)性演化中扮演了比之前科學(xué)界所認(rèn)識(shí)的更為重要的角色。

鳥類獨(dú)特的婚配系統(tǒng)和生態(tài)、行為適應(yīng)為超基因假說提供了最好的例證。雄性流蘇鷸()具有3種截然不同的形態(tài)，包括攻擊性的“independents”、半合作的“satellites”和模仿雌性的“faeders”。研究發(fā)現(xiàn)“independents”為祖先狀態(tài)，“satellites”和“faeders”型的出現(xiàn)是由于11號(hào)染色體中一段長約4.5 Mb包含有125個(gè)基因的區(qū)域發(fā)生了倒位，形成了多種不重組的單倍型。而倒位的一個(gè)斷點(diǎn)影響了編碼著絲粒蛋白基因的表達(dá)，導(dǎo)致了3種不同形態(tài)的雄性型在體型大小、羽色、行為、睪丸大小和類固醇代謝方面的差異[28,29]。而白喉帶鹀()依據(jù)頭部條紋顏色，分為白色條紋型和棕褐色條紋型。Tuttle和團(tuán)隊(duì)經(jīng)過長達(dá)20多年的野外研究，發(fā)現(xiàn)白色條紋的雄性幾乎只與棕褐色條紋的雌性交配(98.53%)，而棕褐色條紋的雄性幾乎只與白色條紋的雌性交配(98.46%)，這種異型交配使得任何個(gè)體都只能有1/4的幾率繁殖成功，繼而造成了類似4種性別的婚配系統(tǒng)的出現(xiàn)[30,31]。在行為上，兩種異型交配方式代表了不同繁殖策略的權(quán)衡，白色條紋的雄性更具攻擊性，很少照顧子代，且往往一夫多妻；而棕褐色條紋的雄性會(huì)照顧子代，且一夫一妻；相同條紋顏色的雌性與雄性表現(xiàn)類似[32]。進(jìn)一步的研究揭示了白色條紋型的ZAL2m染色體發(fā)生了大于100 Mb的倒位，形成包含1137 個(gè)基因的超基因，這些基因中許多都與不同型特異的行為和羽毛顏色相關(guān)[30]。類似地，具有3種生態(tài)型變異的朱頂雀()基因組中存在約55 Mb的染色體倒位，這段倒位使得超基因形成并維持平衡多態(tài)，最終控制了黑色素形成、類胡蘿卜素著色和喙型發(fā)育等多種表型[33]。也有研究發(fā)現(xiàn)長115 Mb的超基因控制了西鵪鶉()表型和行為的變異，攜帶倒位的超基因的種群喉部顏色更深、體重更重、翅膀更圓潤，同時(shí)長距離遷徙能力也發(fā)生丟失或變?nèi)鮗34]。

此外，高度社會(huì)性昆蟲螞蟻分離的性比和社會(huì)性多態(tài)[35,36]、蝴蝶擬態(tài)的發(fā)生[37,38]、受過度開采影響的大西洋鱈魚()對(duì)環(huán)境波動(dòng)的抵抗和洄游的生活方式[39,40]、適應(yīng)不同環(huán)境的向日葵()的生態(tài)分化[41]等也都被證明受到了超基因控制。

1.3 多基因遺傳假說(polygenic inheritance hy-pothesis)

多基因遺傳假說是指適應(yīng)性表型受散布在基因組中的許多基因座控制，通常這些基因的作用是微效的[42]，且可能在特定功能或通路中協(xié)同發(fā)揮作用(圖1C)[43]。這樣的多基因性狀也被稱為數(shù)量性狀或復(fù)雜性狀[44]。早期數(shù)量遺傳學(xué)研究表明許多性狀都是多基因控制的，有助于快速表型適應(yīng)[42]。最近系統(tǒng)生物學(xué)的興起為適應(yīng)性演化研究帶來新的活力。系統(tǒng)生物學(xué)研究強(qiáng)調(diào)了復(fù)雜性狀是受到基因間及其調(diào)控因子間相互作用關(guān)系影響的，認(rèn)為基因調(diào)控網(wǎng)絡(luò)(gene regulatory networks, GRNs)在多基因適應(yīng)演化中起到了重要的作用[44]。

人類的身高、體重和皮膚、頭發(fā)和眼睛的顏色等都被認(rèn)為是最典型的受多基因控制的性狀。生態(tài)學(xué)領(lǐng)域也提出了一系列法則來解釋這些適應(yīng)性表型的變異，如生活在高緯度寒冷地區(qū)的種群體型變大的貝格曼定律、身體突出部分變短變圓的艾倫定律、生活在寒冷干旱地區(qū)的種群皮膚顏色變淺的葛洛格定律[42]。迄今通過GWAS分析已經(jīng)確定了約800個(gè)與身高相關(guān)的常見高頻和罕見低頻變異[45]。有研究表明非洲和亞洲熱帶雨林中狩獵者—采集者趨同的“侏儒”表型是多基因適應(yīng)的結(jié)果，且這些基因主要與“生長因子結(jié)合”和“心臟組織發(fā)育”功能相關(guān)[46]。通過對(duì)皮膚曬黑難易度的GWAS分析，研究人員新報(bào)道了14個(gè)基因，這些基因與色素沉積表型顯著相關(guān)[47]。針對(duì)人類頭發(fā)顏色的GWAS研究，確定了上百個(gè)與顏色相關(guān)的SNP位點(diǎn)，這些位點(diǎn)控制了多種頭發(fā)顏色獨(dú)立的產(chǎn)生[48,49]。研究人員還發(fā)現(xiàn)這些基因中許多不直接參與黑色素生成，而是與頭發(fā)生長或頭發(fā)質(zhì)地相關(guān)，暗示了黑色素細(xì)胞可能與角質(zhì)形成細(xì)胞相互作用一起影響發(fā)色色素沉著[48]。

1.4 非編碼區(qū)調(diào)控假說(noncoding region regu-lation hypothesis)

非編碼區(qū)調(diào)控假說是指基因組中非編碼區(qū)的變異調(diào)控了單一或多種適應(yīng)性表型的形成(圖1D)[50]。King和Wilson在1975年開創(chuàng)性地提出非編碼DNA在人類和非人靈長類動(dòng)物表型差異中具有重要的意義[51]。非編碼區(qū)變異，如順式調(diào)控突變(-regulatory variation)，通常只在特定的時(shí)間和空間發(fā)揮作用，具有更小的基因多效性影響(pleiotropic effects)，更大的進(jìn)化可塑性，同時(shí)可能調(diào)控基因表達(dá)[52]。在自然選擇作用下，活躍增強(qiáng)子的微調(diào)作用為調(diào)控適應(yīng)的發(fā)生提供了可能[53]。有研究表明基因的順式調(diào)控突變導(dǎo)致了袖蝶屬多種蝴蝶表現(xiàn)出紅翅型[54]，而基因的順式調(diào)控突變導(dǎo)致了果蠅屬()多種果蠅雄性產(chǎn)生趨同的特異性色素沉積[55]。類似地，基因的順式調(diào)控增強(qiáng)子突變是導(dǎo)致和形態(tài)趨同的原因[56]。Merritt等[57]通過基因敲低實(shí)驗(yàn)、行為學(xué)實(shí)驗(yàn)，結(jié)合轉(zhuǎn)錄組和甲基化數(shù)據(jù)證實(shí)了白色條紋型的白喉帶鹀基因(編碼雌激素受體α)的順式調(diào)控區(qū)的變異而不是編碼區(qū)的非同義替代，調(diào)控了其基因表達(dá)水平的改變，繼而產(chǎn)生了領(lǐng)域性的攻擊行為。

隨著大量基因組數(shù)據(jù)的公布，保守的非編碼區(qū)(conserved noncoding elements, CNEs)也逐漸成為研究的熱點(diǎn)。針對(duì)于人腦的研究發(fā)現(xiàn)，非編碼區(qū)在人類腦演化中發(fā)揮了至關(guān)重要的作用，非編碼區(qū)的差異是導(dǎo)致人類和非人靈長類動(dòng)物認(rèn)知功能差異的主要原因[58～60]。Sackton等[61]發(fā)現(xiàn)調(diào)控區(qū)(如保守的非外顯子元件)的變異與古顎類物種飛行能力丟失這一性狀的產(chǎn)生密切相關(guān)。Ferris等[62]揭示了不同冬眠動(dòng)物的非編碼區(qū)順式調(diào)控元件發(fā)生了平行選擇作用，這些元件潛在調(diào)控與人類肥胖相關(guān)的基因。對(duì)具有鳴唱能力的鳴禽、鸚鵡和蜂鳥的比較研究發(fā)現(xiàn)，在與語言能力或大腦表達(dá)特化相關(guān)的基因、與神經(jīng)發(fā)育功能相關(guān)的基因、與語言交流障礙相關(guān)的基因的附近都發(fā)現(xiàn)了非編碼區(qū)加速進(jìn)化的信號(hào)，暗示了這些區(qū)域在調(diào)控語言學(xué)習(xí)能力中有潛在作用[63]。但目前大量適應(yīng)性演化的研究仍主要關(guān)注于蛋白編碼基因的變異，忽視了非編碼區(qū)在適應(yīng)性演化中的重要作用，因此無偏地對(duì)全基因組序列分析將有助于全面揭示物種適應(yīng)性演化的機(jī)理。

1.5 重復(fù)序列調(diào)控假說(repeated region regu-lation hypothesis)

重復(fù)序列調(diào)控假說是指基因組中重復(fù)序列，尤其轉(zhuǎn)座子(transposable elements, TEs)的變異調(diào)控了適應(yīng)性表型的形成(圖1E)[64]。重復(fù)序列依據(jù)重復(fù)單元的排列方式分為串聯(lián)重復(fù)序列(tandem repeats)和散在重復(fù)序列(interspersed repeats)。串聯(lián)重復(fù)序列主要分為衛(wèi)星DNA和微衛(wèi)星DNA(簡單重復(fù))；散在重復(fù)序列又稱為轉(zhuǎn)座子，可分為Ⅰ型轉(zhuǎn)座子，即逆轉(zhuǎn)錄轉(zhuǎn)座子(retrotransposons，RNA轉(zhuǎn)座子)和Ⅱ型轉(zhuǎn)座子，即DNA轉(zhuǎn)座子[65]。不同物種基因組中重復(fù)序列的比例有所差異。哺乳動(dòng)物中重復(fù)序列平均約占整個(gè)基因組的34%～52%，而鳥類中重復(fù)序列比例較少，平均約占整個(gè)基因組的4%～10%[10]。

重復(fù)序列的積累或DNA獲得/丟失會(huì)影響基因組大小。Lamichhaney等[66]發(fā)現(xiàn)澳大利亞特有蛙有著比大多鳥類更小的基因組，相比其他具有大基因組的兩棲動(dòng)物，其基因組的減小主要是為了控制轉(zhuǎn)座子擴(kuò)增，這可能與其生活史方式，如快速靈活的蝌蚪發(fā)育和飲食等有關(guān)。重復(fù)序列也可能會(huì)調(diào)控基因表達(dá)，驅(qū)動(dòng)新表型的出現(xiàn)。Van’t Hof 等[64]對(duì)樺尺蛾表型黑化的遺傳基礎(chǔ)展開了進(jìn)一步的研究，揭示了由于一個(gè)大的串聯(lián)重復(fù)轉(zhuǎn)座子插入到基因的第一個(gè)內(nèi)含子，提高了基因的表達(dá)，調(diào)節(jié)了細(xì)胞周期，從而引起了樺尺蛾工業(yè)黑化表型的出現(xiàn)。Goubert等[67]在全基因組范圍內(nèi)檢測(cè)了轉(zhuǎn)座子在不同細(xì)胞類型的順式調(diào)控作用、對(duì)增強(qiáng)子和其他遠(yuǎn)端調(diào)控元件的調(diào)控作用，以及對(duì)轉(zhuǎn)錄后基因表達(dá)的影響等，證明了轉(zhuǎn)座子對(duì)表型變異具有重要作用。

1.6 基因漸滲假說(introgression hypothesis)

基因漸滲假說是指一個(gè)物種的有益遺傳變異通過雜交轉(zhuǎn)移到另一個(gè)物種，從而實(shí)現(xiàn)快速表型適應(yīng)(圖1F)[68]。自然界中遺傳混合(admixture)的頻率很高，廣泛存在于動(dòng)、植物中[41,69]?，F(xiàn)代人類的基因組中也存在古人類尼安德特人和丹尼索瓦人的遺傳信息[70,71]。在白喉帶鹀的研究中還發(fā)現(xiàn)棕褐色條紋型的ZAL2染色體與白色條紋型的ZAL2m染色體倒位的區(qū)域存在很大分化，推測(cè)ZAL2m染色體可能是來自于已滅絕物種與白喉帶鹀歷史上的雜交事件導(dǎo)致的基因漸滲[30]。針對(duì)火蟻屬()的研究，發(fā)現(xiàn)一個(gè)有“多蟻后”社會(huì)形態(tài)的物種中可以抵抗重組作用的超基因區(qū)的變異，通過漸滲雜交被重復(fù)地轉(zhuǎn)移到其他物種，以維持火蟻屬獨(dú)特的社會(huì)等級(jí)和生態(tài)特征[72]。動(dòng)物毛色的季節(jié)性變化也受到基因漸滲的重要影響。北美野兔()通常在冬季換上白色長毛以進(jìn)行偽裝，但在積雪較少的地區(qū)，一些北美野兔會(huì)保持棕色的皮毛。研究表明其與黑尾兔()的種間基因流促使黑尾兔色素沉積基因的滲入，導(dǎo)致冬季多態(tài)性表型的出現(xiàn)[73]。類似地，有研究發(fā)現(xiàn)山野兔()冬季皮毛顏色的多態(tài)性也是由于與其他野兔的雜交而獲得了與特定毛色相關(guān)的等位基因[74]。適應(yīng)性基因漸滲還可以在一定程度上對(duì)物種進(jìn)行進(jìn)化拯救(evolutionary rescue)。受環(huán)境污染影響的大底鳉()通過雜交漸滲從加拿大底鳉()基因組中獲得了一個(gè)包含有缺失的芳香烴受體基因，這阻礙了大底鳉芳香烴受體信號(hào)的轉(zhuǎn)導(dǎo)，從而增強(qiáng)了其對(duì)環(huán)境污染的抵抗能力[75]。

圖1 適應(yīng)性演化遺傳機(jī)制

A：主效基因假說；B：超基因假說；C：多基因遺傳假說；D：非編碼區(qū)調(diào)控假說；E：重復(fù)序列調(diào)控假說；F：基因漸滲假說。CRE：-regulatory element；TE：transposable element。

2 物種對(duì)高海拔極端環(huán)境適應(yīng)

高海拔地區(qū)具有低氧、低溫、強(qiáng)紫外線輻射等典型的環(huán)境特征，因而成為了研究物種極端環(huán)境適應(yīng)性演化的天然實(shí)驗(yàn)室。生活在這種極端環(huán)境下的生物，為應(yīng)對(duì)強(qiáng)的選擇壓力，在表型和遺傳層面發(fā)生了相應(yīng)的適應(yīng)性改變。世界范圍內(nèi)最典型的高海拔環(huán)境包括安第斯高原、埃塞俄比亞高原以及青藏高原。其中，被譽(yù)為“世界屋脊”和“地球第三極”的青藏高原平均海拔在4500 m以上，是全球面積最大、平均海拔最高的高原[76]，長期以來受到國內(nèi)外科學(xué)家的廣泛關(guān)注。隨著組學(xué)技術(shù)的發(fā)展，青藏高原地區(qū)已有大量典型動(dòng)物類群的基因組和適應(yīng)性演化機(jī)制被解析，成為全球高海拔適應(yīng)研究中最具有代表性的區(qū)域。因此，本節(jié)將主要以青藏高原極端環(huán)境適應(yīng)為例，簡要概述不同類群的表型適應(yīng)特征、遺傳適應(yīng)機(jī)制及其主要支持的適應(yīng)性演化分子遺傳假說。

2.1 物種對(duì)高海拔環(huán)境的表型適應(yīng)

早期物種高海拔適應(yīng)的研究主要集中在形態(tài)、生理、生化、行為等表型水平。

人類是高海拔適應(yīng)研究最多和最深入的類群之一。相比僅有短期高原居住史的居民(原低海拔人群)，有著久遠(yuǎn)高海拔適應(yīng)歷史的藏人演化出了更高的靜息通氣和低氧通氣能力以及更低的低氧肺血管收縮和慢性高原病敏感性等特異的表型特征[77]。同時(shí)，不同于通過提高紅細(xì)胞數(shù)目及血紅蛋白(hemoglobin, Hb)濃度來增強(qiáng)氧氣利用率的較短高原居住史的居民，藏人主要通過提高Hb-O2親和力來高效利用氧氣，從而有效避免了由于紅細(xì)胞增多導(dǎo)致的血液黏稠和血栓形成，降低了罹患心臟病等高原疾病的風(fēng)險(xiǎn)[78]。

為適應(yīng)極端環(huán)境壓力，其他高海拔動(dòng)物物種/種群相比其低海拔近緣物種或低海拔種群，也演化出一系列適應(yīng)性表型。高原哺乳動(dòng)物相比低海拔物種/種群，有著顯著更高的心臟與體重比、更低的肺動(dòng)脈壓及更強(qiáng)的低氧適應(yīng)能力[79,80]。對(duì)不同海拔的高原鼢鼠()種群的比較研究發(fā)現(xiàn)，相比于低海拔種群(<3000 m)，高海拔的高原鼢鼠種群(4300 m)的紅細(xì)胞數(shù)目、血紅蛋白濃度以及紅細(xì)胞比容顯著增高，而右心室未發(fā)生肥厚、心肌細(xì)胞未發(fā)生肥大，暗示著心臟功能的增強(qiáng)[80]。對(duì)高低海拔不同種群的拉布拉多白足鼠()肌肉表型的研究發(fā)現(xiàn)，高海拔種群的腓腸肌有更高比例的氧化型纖維和毛細(xì)血管密度[81]。

普遍具飛行能力的鳥類也表現(xiàn)出許多高海拔適應(yīng)性特征。例如，分布于青藏高原的地山雀、褐冠山雀()、黑冠山雀()及黑眉長尾山雀()相比各自近緣的低海拔物種，都顯著提高了Hb-O2親和力[82]。在青藏高原輻射成種的雀形目鳥類——雪雀類群(snowfinches)和近緣的低海拔樹麻雀()的比較研究中發(fā)現(xiàn)，相比低海拔樹麻雀，高海拔雪雀整體上有著更大的體重、心臟與體重比和飛行肌與體重比[83～85]，以及更高的線粒體體積密度、胰島素敏感性和需氧代謝能力[83]。但同時(shí)由于生態(tài)位競(jìng)爭，這些同域分布的雪雀在形態(tài)、生理和行為等表型上也出現(xiàn)了一定程度的適應(yīng)性分化[84,86]。此外，Shao等[87]結(jié)合幾何形態(tài)學(xué)和物種的系統(tǒng)發(fā)育關(guān)系，發(fā)現(xiàn)青藏高原特有種地山雀為適應(yīng)高原開闊的生境，演化出區(qū)別于其他山雀類群的長而下彎的喙和相對(duì)較長的跗跖，以便于其地面活動(dòng)和覓食。

高海拔棲息的較為低等變溫動(dòng)物的魚類、兩棲類和爬行類，也發(fā)生了許多適應(yīng)性表型變化，包括降低總代謝速率，即抑制代謝；增強(qiáng)對(duì)代謝副產(chǎn)物，如質(zhì)子等的耐受；增強(qiáng)細(xì)胞損傷修復(fù)的能力來抵御組織氧氣供應(yīng)的不足等[88]。

整體來看，適應(yīng)于高海拔環(huán)境的物種/類群有著趨同的表型適應(yīng)特征，如更強(qiáng)的低氧、低溫等耐受能力及更強(qiáng)的心血管功能，也有著趨異的物種/類群獨(dú)特的表型適應(yīng)特征。

2.2 物種對(duì)高海拔環(huán)境的遺傳適應(yīng)

遺傳的適應(yīng)可以驅(qū)動(dòng)適應(yīng)性表型的形成。自分子生物學(xué)興起以來，科研人員們對(duì)物種高海拔適應(yīng)的遺傳機(jī)制進(jìn)行了長期的探索。由于早期測(cè)序技術(shù)的限制，分子機(jī)制的研究主要集中于血紅蛋白、細(xì)胞色素C氧化酶(cytochrome c oxidase, COX)等少數(shù)與高海拔適應(yīng)功能相關(guān)的基因[82,89～91]。高海拔類群的這些蛋白編碼基因某些位點(diǎn)的非同義氨基酸突變，可能會(huì)造成蛋白的結(jié)構(gòu)變異，繼而影響到O2的運(yùn)輸能力和氧化磷酸化過程中O2的還原。特別地，在不同的高海拔物種間發(fā)現(xiàn)Hb-O2親和力趨同增加，可能是由于血紅蛋白基因中某些相同位點(diǎn)的氨基酸趨同的改變[82,91]，也可能是由于不同位點(diǎn)氨基酸的改變[82,90]，且不同氨基酸替代所引起的變構(gòu)調(diào)節(jié)機(jī)制也可能不同[82]。隨著高通量測(cè)序和組學(xué)技術(shù)的發(fā)展和成熟，研究人員可以針對(duì)多種類群從全基因組水平挖掘與適應(yīng)相關(guān)的遺傳信號(hào)。表1匯總了不同類群高海拔適應(yīng)研究所使用的測(cè)序技術(shù)及主要支持的假說。

利用群體基因組學(xué)研究方法以及先驗(yàn)知識(shí)(潛在候選基因集)，Simonson等[92]在全基因組水平鑒定了與藏人高海拔適應(yīng)相關(guān)的正選擇區(qū)域，其中和單倍型的變異與其血紅蛋白濃度降低顯著相關(guān)。同期，Beall等[93]發(fā)現(xiàn)()中有多個(gè)SNPs發(fā)生了連鎖不平衡，與藏人血紅蛋白濃度降低也顯著相關(guān)。Peng等[94]發(fā)現(xiàn)藏人的變異不僅和血紅蛋白濃度降低有關(guān)，還和肺血管收縮響應(yīng)變?nèi)跤嘘P(guān)。Lorenzo等[95]還發(fā)現(xiàn)中兩個(gè)突變(12C>G和380G>C)在阻止低氧誘導(dǎo)和HIF介導(dǎo)的紅細(xì)胞增多中也發(fā)揮了作用。而Yang等[96]對(duì)藏人和東亞非藏人的上萬個(gè)體進(jìn)行基因組掃描，鑒定到了9個(gè)高海拔適應(yīng)基因，其中和與藏人血液相關(guān)表型，如血紅蛋白、同型半胱氨酸和葉酸的濃度強(qiáng)烈相關(guān)?；騬s1801133位與葉酸增加相關(guān)的等位基因頻率在藏人中發(fā)生了比隨機(jī)預(yù)期更顯著的提高，可能與藏人高紫外輻射適應(yīng)功能相關(guān)。等主效基因的變異很好地揭示了藏人高海拔低氧適應(yīng)的遺傳基礎(chǔ)。最近，Xu等[79]通過結(jié)合比較基因組學(xué)和功能實(shí)驗(yàn)，證實(shí)了高海拔哺乳動(dòng)物基因中氨基酸的改變(Q247R)驅(qū)動(dòng)了其更大的心臟和更粗的肺動(dòng)脈的形成，從而增強(qiáng)了高原低氧適應(yīng)能力。這些高海拔適應(yīng)機(jī)制主要支持了主效基因假說。

表1 高海拔適應(yīng)研究的典型實(shí)例匯總

續(xù)表

然而，針對(duì)更多高海拔特有的動(dòng)物類群的研究發(fā)現(xiàn)，高海拔適應(yīng)是一個(gè)極端復(fù)雜的性狀，主效基因可能不能完全解釋高海拔適應(yīng)機(jī)理，而更可能是遵循多基因或功能/通路/調(diào)控網(wǎng)絡(luò)水平適應(yīng)的規(guī)律，支持多基因遺傳假說。哺乳類，如牦牛()[97]、金絲猴()[98]、藏灰狼()[99]和高原鼢鼠[80]；鳥類，如地山雀[100,101]、山雀[101]、雪雀[85]、樹麻雀[43]、綠尾虹雉()[102]、黑頸鶴()[103]和四川雉鶉()[104]；魚類，如厚唇裸重唇魚()[105]和高原鰍()[106,107]；兩棲類，如高山倭蛙()[108,109]；爬行類，如沙蜥()[109]和溫泉蛇()[110]等物種都檢測(cè)到多個(gè)與低氧響應(yīng)、能量代謝和DNA修復(fù)等功能相關(guān)的正選擇或加速進(jìn)化基因，以應(yīng)對(duì)低氧、低溫以及強(qiáng)紫外輻射等極端環(huán)境條件。

物種高海拔適應(yīng)的研究多集中在DNA序列水平，而蛋白編碼序列的變異可能不直接影響基因表達(dá)的變化，而基因表達(dá)的改變?cè)谖锓N適應(yīng)性演化中有著重要的作用[111～114]。Yu等[98]發(fā)現(xiàn)高海拔金絲猴在對(duì)極端環(huán)境和飲食適應(yīng)過程中，能量消耗的組織(心臟、骨骼肌)和負(fù)責(zé)消化的組織(小腸、大腸、胃)的高表達(dá)基因集發(fā)生了特異的表達(dá)譜轉(zhuǎn)變。針對(duì)3對(duì)近緣的高低海拔山雀、長尾山雀的比較轉(zhuǎn)錄組研究發(fā)現(xiàn)，高海拔類群在多個(gè)組織中都發(fā)生了適應(yīng)性的趨同改變，且這種基因表達(dá)的改變與其表型適應(yīng)，如高海拔鳥類具有更大的體型、更長的跗跖顯著相關(guān)[115]。進(jìn)一步研究發(fā)現(xiàn)高海拔適應(yīng)相關(guān)的正選擇基因和差異表達(dá)基因只有很少部分的交集，暗示了非編碼區(qū)在調(diào)控基因表達(dá)中發(fā)揮了重要作用[115]。Xin等[53]結(jié)合RNA-seq、ATAC-seq等多組學(xué)數(shù)據(jù)，開發(fā)了vPECA(variant interpretation methodology)方法證明了非編碼區(qū)調(diào)控元件的變異影響了相關(guān)轉(zhuǎn)錄因子的結(jié)合，繼而下調(diào)了的表達(dá)，從而改變了的低氧響應(yīng)和血管再生調(diào)控網(wǎng)絡(luò)。這些研究則主要支持了非編碼區(qū)調(diào)控假說。

基因漸滲假說在高海拔適應(yīng)性演化中也得到證實(shí)。有研究表明藏人的高海拔適應(yīng)一定程度上是源自于丹尼索瓦人樣的DNA漸滲[116]。類似地，藏獒快速高海拔低氧適應(yīng)能力的獲得也可能由于藏灰狼的基因漸滲[117]。而超基因假說和重復(fù)序列調(diào)控假說是否可以解釋高海拔適應(yīng)性演化還有待進(jìn)一步的研究。

此外，有著物種“第二基因組”美譽(yù)的腸道微生物在高海拔適應(yīng)中也發(fā)揮了潛在的作用。Zhang等[118]比較了高海拔牦牛、藏綿羊和近緣低海拔物種的瘤胃微生物，發(fā)現(xiàn)高海拔類群之間有著類似的微生物群落結(jié)構(gòu)和組成，且顯著提高了揮發(fā)性脂肪酸的產(chǎn)生和顯著降低了甲烷的產(chǎn)生，同時(shí)相似的通路

也被鑒定出來，暗示了微生物與宿主共進(jìn)化以適應(yīng)高海拔極端環(huán)境。Bo等[119]對(duì)高海拔鳥類腸道微生物的研究發(fā)現(xiàn)，不同高原鳥類的腸道菌群均主要由厚壁菌門、藍(lán)藻菌門和變形菌門組成，其中厚壁菌門與揮發(fā)性脂肪酸的合成有關(guān)，這可能參與了高海拔類群能量代謝通路的調(diào)控。

3 適應(yīng)性演化領(lǐng)域現(xiàn)存的主要挑戰(zhàn)

3.1 方法論的更新

適應(yīng)性變異的檢測(cè)方法和相關(guān)方法論已經(jīng)相對(duì)成熟，但目前分析方法多針對(duì)于編碼區(qū)。一方面是由于蛋白編碼基因在功能上通常有重要作用；另一方面它相對(duì)保守、易于檢測(cè)，可以應(yīng)用分子進(jìn)化領(lǐng)域的框架和理論。而越來越多的研究表明基因組中占比更大的非編碼區(qū)和重復(fù)序列等在適應(yīng)性演化中也發(fā)揮著重要的調(diào)控作用。目前針對(duì)于非編碼區(qū)的研究方法多聚焦在保守的非編碼元件[59,120]，而非保守的非編碼元件也可能具有重要作用。Wang等[121]開發(fā)了功夫熊貓方法(Kung-Fu Panda, KFP)，基于泊松概率(Poisson probability)檢驗(yàn)將加速進(jìn)化的檢測(cè)擴(kuò)展到了非保守的區(qū)域。未來應(yīng)有更多針對(duì)于非編碼區(qū)和重復(fù)序列加速進(jìn)化的檢測(cè)方法被開發(fā)和應(yīng)用。

3.2 基因型和表型的關(guān)聯(lián)

在種內(nèi)水平，盡管數(shù)量遺傳學(xué)和群體遺傳學(xué)利用數(shù)量性狀基因座定位(quantitative trait locus map-ping, QTL)和GWAS等方法建立起了基因型和表型數(shù)據(jù)的關(guān)聯(lián)，但這些分析大都需要一個(gè)物種多個(gè)個(gè)體、群體或生態(tài)型的樣品，并要求大量樣本和1對(duì)1的基因型和表型對(duì)應(yīng)的數(shù)據(jù)，這對(duì)于非模式物種很難實(shí)現(xiàn)。在種上水平，表型和基因型的連接變得更加困難。通常的物種水平研究都假定單個(gè)具有特殊表型或具有類似表型(趨同演化)的物種因受到潛在的選擇作用，相比于其他對(duì)比物種在序列水平發(fā)生了特定的改變，繼而分析這些改變?cè)谶m應(yīng)性表型中可能發(fā)揮的功能，以建立起基因型和表型的潛在聯(lián)系。有研究將蛋白編碼基因的非同義替代速率/同義替代速率(ratio of nonsynonymous substitutions per nonsynonymous site to synonymous substitutions per synonymous site, dN/dS)與表型數(shù)據(jù)或潛在影響表型的基因表達(dá)數(shù)據(jù)，進(jìn)行相關(guān)分析[122～124]；最近也有整合模型嘗試建立表型的改變和位點(diǎn)特異性序列進(jìn)化之間的聯(lián)系[125]。但這樣的間接推測(cè)或關(guān)聯(lián)分析很難真正揭示基因的變異在表型改變中起到的作用。因此，相關(guān)的實(shí)驗(yàn)方案、分析及統(tǒng)計(jì)方法和研究思路需要不斷探索、發(fā)展和優(yōu)化。

3.3 基因表達(dá)可塑性的作用

可塑性近些年成為進(jìn)化遺傳學(xué)和適應(yīng)性演化領(lǐng)域中重要的研究主題之一。其中有兩個(gè)最關(guān)鍵的科學(xué)問題：一個(gè)是檢測(cè)可塑性和遺傳變異在適應(yīng)演化中的相對(duì)作用；另一個(gè)是評(píng)估可塑性在適應(yīng)、馴化(acc-limation)和不良適應(yīng)(maladaptation)中的作用[126～129]。基因表達(dá)具有時(shí)間(包括不同發(fā)育階段)、空間特異性，因此對(duì)基因表達(dá)的調(diào)控有助于物種可塑性地快速響應(yīng)環(huán)境變化或拓殖到新生境[130]。但由于實(shí)驗(yàn)條件和技術(shù)的限制，目前野生類群很少開展實(shí)驗(yàn)，區(qū)分基因表達(dá)的變化是響應(yīng)局域環(huán)境的可塑性改變還是進(jìn)化的可塑性改變(具有遺傳學(xué)基礎(chǔ))[115]。最近有研究結(jié)合細(xì)胞的轉(zhuǎn)錄表達(dá)和群體的遺傳分化探究了短期應(yīng)激和長期適應(yīng)的關(guān)系，發(fā)現(xiàn)這兩個(gè)過程有著相似的響應(yīng)途徑，暗示了短期應(yīng)激可能促進(jìn)了適應(yīng)的發(fā)生[131]。未來野生類群同質(zhì)園實(shí)驗(yàn)(common garden experiment)或相互移植實(shí)驗(yàn)(reciprocal transplant experiment)的技術(shù)突破將有助于更好地理解基因表達(dá)可塑性在適應(yīng)性演化中的作用[43,80,86,132]。

3.4 非模式體系的實(shí)驗(yàn)驗(yàn)證

組學(xué)技術(shù)作為強(qiáng)有力的工具可以幫助科研人員快速挖掘與適應(yīng)性表型相關(guān)的遺傳信號(hào)，但現(xiàn)有的統(tǒng)計(jì)方法或模型都具有一定的局限性，這就導(dǎo)致了分析結(jié)果中不可避免地存在假陽性。因此，進(jìn)行相關(guān)的實(shí)驗(yàn)驗(yàn)證尤為重要。目前針對(duì)篩選到的信號(hào)的功能實(shí)驗(yàn)驗(yàn)證主要依賴于模式體系，包括利用已有的成熟細(xì)胞系和小鼠、果蠅、斑馬魚、酵母、雞等模式動(dòng)物的模型。而非模式物種如果直接利用現(xiàn)有的模式體系進(jìn)行實(shí)驗(yàn)驗(yàn)證，可能會(huì)受到所使用的模式物種的遺傳背景的干擾，從而無法獲得最直接的功能證據(jù)，甚至可能得到一些不可靠的結(jié)論。所以，亟需構(gòu)建非模式物種本身或近緣物種的實(shí)驗(yàn)體系。最近，Qu等[85]構(gòu)建了野生鳥類大山雀()的胚胎成纖維細(xì)胞系，證實(shí)了高海拔雪雀類群基因的非同義突變明顯增強(qiáng)了其DNA損傷修復(fù)能力。但總體來看，構(gòu)建非模式物種的實(shí)驗(yàn)體系仍面臨著諸多的挑戰(zhàn)，而CRISPR/Cas9基因編輯技術(shù)的發(fā)展和應(yīng)用使非模式體系實(shí)驗(yàn)驗(yàn)證成為了可能。

4 結(jié)語與展望

物種的適應(yīng)性演化是進(jìn)化生物學(xué)和生態(tài)學(xué)領(lǐng)域研究的核心問題。研究物種的適應(yīng)性演化分子遺傳機(jī)制有助于深入理解物種多樣性形成機(jī)制，對(duì)于生物多樣性保護(hù)和種質(zhì)資源保存具有重要意義。目前，已針對(duì)不同類群獨(dú)特的形態(tài)、生理生化、組織結(jié)構(gòu)和行為等表型的遺傳機(jī)制進(jìn)行了廣泛探索。依據(jù)目前的研究進(jìn)展，關(guān)于適應(yīng)性演化的分子遺傳機(jī)制的假說大體包括主效基因、超基因、多基因遺傳、非編碼區(qū)調(diào)控、重復(fù)序列調(diào)控、基因漸滲等。高海拔極端環(huán)境為物種適應(yīng)性演化提供了天然實(shí)驗(yàn)室，塑造了高原生物獨(dú)特的表型特征。當(dāng)物種不能適應(yīng)這種極端環(huán)境時(shí)，就可能出現(xiàn)肺水腫、腦水腫、心臟病等高原疾病。因此，研究極端環(huán)境中的土著物種如何適應(yīng)和演化，對(duì)于研究相關(guān)疾病或癌癥的發(fā)病機(jī)制具有潛在的醫(yī)學(xué)意義。

如前所述，目前適應(yīng)性演化領(lǐng)域仍存在諸多亟待解決的重要科學(xué)問題。分析方法的改進(jìn)、組學(xué)技術(shù)的發(fā)展和實(shí)驗(yàn)手段的完善將有助于解決這些困難。適應(yīng)的發(fā)生往往不局限在單一層面，而是反映在細(xì)胞、生理生化、酶學(xué)、組織學(xué)、形態(tài)、行為等多個(gè)層面、多個(gè)維度。相應(yīng)地，分子遺傳機(jī)制也往往支持多種不同的假說。因此，聯(lián)合表型組、基因組(包括群體)、轉(zhuǎn)錄組(包括單細(xì)胞)、蛋白組、代謝組、微生物組、表觀組(如ChIP-seq和ATAC-seq)等組學(xué)數(shù)據(jù)，結(jié)合CRISPR/Cas9基因編輯等功能實(shí)驗(yàn)，多維度解析適應(yīng)性演化的機(jī)制必將成為未來的發(fā)展趨勢(shì)。

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Genetic mechanism of adaptive evolution: the example of adaptation to high altitudes

Yan Hao1, Fumin Lei1,2,3

Since Darwin?s time, elucidating the mechanism of adaptive evolution has been one of the most important scientific issues in evolutionary biology and ecology. Adaptive evolution usually means that species evolve special phenotypic traits to increase fitness under selective pressures. Phenotypic adaptation can be observed at different hierarchical levels of morphology, physiology, biochemistry, histology, and behavior. With the breakthroughs of molecular biology and next-generation sequencing technologies, mounting evidence has uncovered the genetic architecture driving adaptive complex phenotypes. Studying the molecular genetic mechanisms of evolutionary adaption will enable us to understand the forces shaping biodiversity and set up genotype-phenotype-environment interactions. Genetic bases of adaptive evolution have been explained by multiple hypotheses, including major-effect genes, supergenes, polygenicity, noncoding regions, repeated regions, and introgression. The strong selection pressure exerted by high-altitude extreme environments greatly promotes the occurrence of phenotypic and genetic adaptation in species. Studies on multi-omics data provide new insights into adaptive evolution. In this review, we systematically summarize the genetic mechanism of adaptive evolution, research progress in adaptation to high-altitude environmental conditions, and existing challenges and discuss the future perspectives, thereby providing guidance for researchers in this field.

phenotype; noncoding region; multi-omics; regulation; high altitudes

2022-04-13;

2022-06-25;

2022-07-19

國家自然科學(xué)基金項(xiàng)目(編號(hào)：32100332，3213000355)，第二次青藏高原綜合科學(xué)考察研究項(xiàng)目(編號(hào)：2019QZKK0304)，青年人才托舉工程項(xiàng)目(編號(hào)：2021QNRC001)和中國博士后科學(xué)基金(編號(hào)：2021M700144)資助[Supported by the National Natural Science Foundation of China (Nos. 32100332, 3213000355), the Second Tibetan Plateau Scientific Expedition and Research (STEP) Program (No. 2019QZKK0304), the Young Elite Scientists Sponsorship Program by CAST (No. 2021QNRC001), and the China Postdoctoral Science Foundation (No. 2021M700144)]

郝艷，博士，研究方向：鳥類適應(yīng)性進(jìn)化。E-mail: haoyan@ioz.ac.cn

雷富民，研究員，博士生導(dǎo)師，研究方向：鳥類學(xué)。E-mail: leifm@ioz.ac.cn

10.16288/j.yczz.22-108

(責(zé)任編委: 于黎)