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脊椎動物のゲノムに存在するボルナウイルスの分子化石を用いた古ウイルス学研究

川崎, 純菜 京都大学 DOI:10.14989/doctor.k24049

2022.03.23

概要

私たち生物のゲノムには、進化過程に感染したウイルスに由来する遺伝配列、内在性ウイルス様エレメント、が多数存在している。本論文は、公共のゲノムデータベースを用いて、RNAウイルスであるボルナウイルスに由来する内在性ウイルス様エレメント( Endogenous bornavirus-like elements: EBLs)を網羅的に検索し、バイオインフォマティクス解析を行なうことで、太古におけるボルナウイルスの感染年代、流行時期、そして宿主域に関して推定を試みたものである。

申請者は、まず969種の真核生物のゲノム情報から、ボルナウイルス科に属するウイルスと相同性を持つ遺伝配列を網羅的に探索した。また、検出された配列の再構築を行うことで、総計で1,465のEBL配列を131種の脊椎動物において同定した。解析の結果、同定されたEBLsのうち、半数以上がこれまでには検出されていなかったものであることが明らかとなった。さらに申請者は、EBLsを有する近縁種間での遺伝子オーソロジー解析を実施することで、それぞれのEBLsの各系統ゲノムへの挿入時期を推定した。その結果、ボルナウイルス感染は古くは約1億年前の白亜紀において、北方真獣類の共通祖先で発生していたことが明らかとなった。また、それ以降も多様な哺乳動物の系統で異なる属に属するボルナウイルスの感染が頻繁に起こっていたことが示された。これらの結果より、太古から現代に至るまで、多くの哺乳動物においてボルナウイルス感染流行が繰り返し起こってきたことを示した。

さらに本研究では、霊長目の系統に着目し詳細な解析を進めた。その結果、霊長目の祖先では、約3,000万年前までは、ボルナウイルス感染が繰り返し発生していたことが明らかとなった。一方、霊長目のゲノムで発見されたEBLsの系統解析により、私たちの祖先には少なくとも6つの異なる系統のボルナウイルスが異なる時代に感染していたことも示された。また、霊長目とコウモリゲノムに見つかったEBLsの解析から、遺伝的に近縁のボルナウイルスが同時期に霊長目とコウモリの祖先に感染していた可能性が示めされ、太古における異種間のウイルス伝播が示唆された。

本論文では、脊椎動物におけるボルナウイルス科ウイルスに由来する内在性ウイルス配列をこれまでにない深度で解析することに成功した。さらに、哺乳動物におけるボルナウイルスの流行状況について地質学的スケールで明らかにすることができた。霊長目動物のゲノムにおけるRNAウイルス由来内在性配列の存在はボルナウイルスのみが知られている。本研究によりヒトを含む霊長目のボルナウイルス感染・流行の歴史が初めて詳細に明らかになった。また、進化過程におけるRNAウイルスと宿主との共存関係や流行発生に関しても新しい知見を与えた。

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