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キツネザル科における食性適応に伴う苦味受容体TAS2R16の機能進化

糸井川, 壮大 京都大学 DOI:10.14989/doctor.k23051

2021.03.23

概要

哺乳類は、口腔内に発現する苦味受容体TAS2Rを介して食物中の潜在的な毒物を苦味として検知することで、適切な食物選択を行っている。TAS2R遺伝子のレパート リーは種によって様々で、進化の過程で柔軟にレパートリーを変化させることで、生息環境に適応し、種固有の苦味感覚を形作っていると考えられている。個々のTAS2Rのリガンド応答性の進化も食性適応には重要と考えられるが、こちらは知見がまだ多くない。そこで、本研究では、狭鼻猿類で青酸配糖体などのβグルコシド化合物を受容することが知られる苦味受容体TAS2R16 について、果実中心食性(果実食性または果実・葉食性)の種と竹食性の種を含むキツネザル科を対象として「霊長類におけるリガンド応答性の進化傾向」と「リガンド応答性と食性の関連」の2点を受容体機能解析や行動アッセイによって検討した。まず、果実中心食性のキツネザル3 種(ワオキツネザルLemur catta、クロキツネザルEulemur macaco、クロシロエリマキキツネザルVarecia variegata)のTAS2R16 についてsalicinやarbutinなどのβグルコシドに対する応答を細胞アッセイで測定した。その結果、ワオキツネザルは狭鼻猿類と同様にすべてのβグルコシドで活性化される一方で、その他2種はsalicinで活性化されるものの、arbutinで不活性化されることを発見した。変異体解析によって、この応答の種間差は曲鼻猿類固有の282 番アミノ酸の置換(L282S)が原因であり、ワオキツネザルは復帰突然変異(S282L)によって狭鼻猿類と同じ応答性を実現していることを明らかにした。これらの結果から、TAS2R16 は霊長類全体でβグルコシドに応答するという保存的傾向がある一方で、同一科内でも個々のリガンドに対する反応パターンは多様であることが示された。

次に、青酸配糖体を含むタケ類(タケ亜科Bambusoideaeに属する植物)を主食とするジェントルキツネザル3 種(ヒロバナジェントルキツネザルProlemur simus、キンイロジェントルキツネザルHapalemur aureus、ハイイロジェントルキツネザルH. grise us)のTAS2R16 について、βグルコシドに対する応答を細胞アッセイで測定した。その結果、TAS2R16 が総じてβグルコシドに対して低い感受性を持つことを明らかにした。また、最尤推定したジェントルキツネザルの最近共通祖先(last common ancesto r: LCA)のTAS2R16でも同様にβグルコシドに対する応答を測定し、現生ジェントルキツネザルとワオキツネザルの中間程度の感受性を持っていたことを明らかにした。さらに、変異体解析によって、ヒロバナジェントルキツネザルとハイイロジェントルキツネザルの低感受性がそれぞれの種固有のアミノ酸置換(ヒロバナジェントルキツネザル:S144L, ハイイロジェントルキツネザル:L251S)によって実現されていることを明らかにした。これらの結果から、ジェントルキツネザルが竹食への適応としてTA S2R16のβグルコシド感受性が低下し、タケ類に苦味を感じにくくなっていることが示唆された。そして、ジェントルキツネザルにおけるβグルコシド感受性の低下は、LC Aの時点で始まっており、Prolemur属とHapalemur属が分岐した後に並行的にさらに進行したものと考えられた。本研究で示した霊長類TAS2R16 における機能の保存的進化とキツネザルで見られた食性に応じた系統固有の機能変化は、食性適応の背景にあ
る味覚適応の分子メカニズムの解明の重要な手がかりとなると考えられる。

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