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净化选择可消除假剪接信号，从而导致多嘧啶区碱基组成的进化。

Purifying selection against spurious splicing signals contributes to the base composition evolution of the polypyrimidine tract.

机构信息

Department of Biomedical Sciences, Vetmeduni Vienna, Vienna, Austria.

Vienna Graduate School of Population Genetics, Vienna, Austria.

出版信息

J Evol Biol. 2023 Sep;36(9):1295-1312. doi: 10.1111/jeb.14205. Epub 2023 Aug 11.

DOI:10.1111/jeb.14205
PMID:37564008
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10946897/
Abstract

Among eukaryotes, the major spliceosomal pathway is highly conserved. While long introns may contain additional regulatory sequences, the ones in short introns seem to be nearly exclusively related to splicing. Although these regulatory sequences involved in splicing are well-characterized, little is known about their evolution. At the 3' end of introns, the splice signal nearly universally contains the dimer AG, which consists of purines, and the polypyrimidine tract upstream of this 3' splice signal is characterized by over-representation of pyrimidines. If the over-representation of pyrimidines in the polypyrimidine tract is also due to avoidance of a premature splicing signal, we hypothesize that AG should be the most under-represented dimer. Through the use of DNA-strand asymmetry patterns, we confirm this prediction in fruit flies of the genus Drosophila and by comparing the asymmetry patterns to a presumably neutrally evolving region, we quantify the selection strength acting on each motif. Moreover, our inference and simulation method revealed that the best explanation for the base composition evolution of the polypyrimidine tract is the joint action of purifying selection against a spurious 3' splice signal and the selection for pyrimidines. Patterns of asymmetry in other eukaryotes indicate that avoidance of premature splicing similarly affects the nucleotide composition in their polypyrimidine tracts.

摘要

在真核生物中，主要的剪接体途径高度保守。虽然长内含子可能包含额外的调节序列，但短内含子中的调节序列似乎几乎完全与剪接有关。尽管这些参与剪接的调节序列已得到很好的描述，但它们的进化情况知之甚少。在内含子的 3' 端，剪接信号几乎普遍包含二聚体 AG，由嘌呤组成，并且该 3' 剪接信号上游的多嘧啶序列的特征是嘧啶过度表达。如果多嘧啶在多嘧啶序列中的过度表达也是由于避免过早的剪接信号，我们假设 AG 应该是最被低估的二聚体。通过使用 DNA 链不对称模式，我们在果蝇属的果蝇中证实了这一预测，并通过将不对称模式与一个假定的中性进化区域进行比较，我们量化了作用于每个基序的选择强度。此外，我们的推断和模拟方法表明，多嘧啶序列的碱基组成进化的最佳解释是针对虚假 3' 剪接信号的纯化选择以及对嘧啶的选择的联合作用。其他真核生物中不对称模式表明，类似地，避免过早剪接也会影响其多嘧啶序列中的核苷酸组成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/174f95c87a95/JEB-36-1295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/ed9df301412e/JEB-36-1295-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/af6aa40233fe/JEB-36-1295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/f6639c55774b/JEB-36-1295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/efe8fec941c5/JEB-36-1295-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/073a2a645ff4/JEB-36-1295-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/174f95c87a95/JEB-36-1295-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/ed9df301412e/JEB-36-1295-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/2751dfa3b1e8/JEB-36-1295-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/0b80068910be/JEB-36-1295-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/6613a17baf6a/JEB-36-1295-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/f20771ba345e/JEB-36-1295-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/af6aa40233fe/JEB-36-1295-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/f6639c55774b/JEB-36-1295-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/efe8fec941c5/JEB-36-1295-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/073a2a645ff4/JEB-36-1295-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4dcd/10946897/174f95c87a95/JEB-36-1295-g005.jpg

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