古代と近代のゲノムを通して,CCR5delta32の削除の進化史を追跡する
Kirstine Ravn1, Leonardo Cobuccio1, Rasa Audange Muktupavela2
1Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Cell
|May 6, 2025
まとめ
CCR5-delta32変種はHIV耐性に関連しており 6,700年以上前に西ユーラシアで発生しました この遺伝的削除はポジティブな選択を経験し,その拡散と治療目標に影響を与えました.
科学分野:
- 人口遺伝学
- 人間 の 進化
- ゲノミクス
背景:
- CCR5-delta32アレルはHIV-1耐性に関連しており,特にヨーロッパの人口におけるその頻度は議論の余地があります.
- CCR5-delta32のような遺伝子変異の起源と広がりを理解することは 進化研究と治療開発に不可欠です
研究 の 目的:
- CCR5-delta32 削除の進化史と時空起源を明らかにする.
- CCR5-delta32ハプロタイプに作用する選択的圧力を調査する.
- ラテンアメリカにおけるCCR5-デルタ32の存在とそのCCR5受容体ベースの治療への影響について説明する.
主な方法:
- 84の既存の変数を活用したハプロタイプ認識の確率モデルを開発した.
- CCR5-delta32の消去の起源を追跡するために 934の低カバーの古代ゲノムをスクリーニングしました.
- CCR5-delta32ハプロタイプに作用する陽性選択を特定するために古代DNAデータを分析した.
主要な成果:
- CCR5-delta32の削除は,少なくとも6700年前に西ユーラシアの草原で特定のハプロタイプで発生した.
- 西欧アジアにおけるCCR5-delta32ハプロタイプにおけるポジティブな選択の強い証拠は,紀元前8,000年から2,000年の間に存在した.
- ラテンアメリカにおけるCCR5-delta32の存在は,コロンビア後における遺伝的混合に起因する.
結論:
- この研究は,CCR5-delta32の削除の詳細な進化のタイムラインを提供し,その根源を古代西ユーラシアに辿ります.
- ポジティブな選択は,CCR5-delta32ハプロタイプの分布を著しく形作りました.
- 複合的な遺伝子型-ハプロタイプ-フェノタイプ関係は,CCR5を標的とする治療戦略を慎重に検討する必要がある.
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