Reverse polarization in amino acid and nucleotide substitution patterns between human-mouse orthologs of two compositional extrema.

Reverse polarization in amino acid and nucleotide substitution patterns between human-mouse orthologs of two compositional extrema.
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DOI:
10.1093/dnares/dsm015
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发表时间:
2007-08-31
期刊:
DNA research : an international journal for rapid publication of reports on genes and genomes
影响因子:
--
通讯作者:
Dutta C
Dutta C
中科院分区:
其他
文献类型:
--
作者:
Bag SK;Paul S;Ghosh S;Dutta C

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对 12 024 个人-小鼠直系同源对的序列差异模式进行全基因组分析,首次揭示了高和低 GC 组成的直向同源物中核苷酸和氨基酸取代的趋势是高度不对称的,并且极化方向相反。根据人类基因第三个密码子位点的GC含量,整个数据集分为三组:高、中、低。从小鼠到人类,高 GC 直向同源物表现出显着偏向于替代的倾向,即 Thr → Ala、Ser → Ala、Val → Ala、Lys → Arg、Asn → Ser、Ile → Val 等,而在低 GC 直向同源物中,则存在相反的趋势。一般来说,在高GC组中,小鼠蛋白质中富含A/U的密码子编码的残基倾向于被人类直系同源中相对富含G/C的密码子编码的残基所取代,而在低GC直系同源对中观察到相反的趋势。中 GC 组与高 GC 组有一些共同趋势,也有一些与低 GC 组相同的趋势。无论 GC 偏差如何,所有直向同源组中共同的唯一显着趋势是 (Asp) 小鼠 → (Glu) 人类替代。在核苷酸水平上,高 GC 直系同源物在每个密码子位置都经历了比 (G/C) 小鼠 → (A/T) 人类大量过量的 (A/T) 小鼠 → (G/C) 人类替换,而对于低 GC 直系同源物,则相反。
Genome-wide analysis of sequence divergence patterns in 12 024 human–mouse orthologous pairs reveals, for the first time, that the trends in nucleotide and amino acid substitutions in orthologs of high and low GC composition are highly asymmetric and polarized to opposite directions. The entire dataset has been divided into three groups on the basis of the GC content at third codon sites of human genes: high, medium, and low. High-GC orthologs exhibit significant bias in favor of the replacements, Thr → Ala, Ser → Ala, Val → Ala, Lys → Arg, Asn → Ser, Ile → Val etc., from mouse to human, whereas in low-GC orthologs, the reverse trends prevail. In general, in the high-GC group, residues encoded by A/U-rich codons of mouse proteins tend to be replaced by the residues encoded by relatively G/C-rich codons in their human orthologs, whereas the opposite trend is observed among the low-GC orthologous pairs. The medium-GC group shares some trends with high-GC group and some with low-GC group. The only significant trend common in all groups of orthologs, irrespective of their GC bias, is (Asp)Mouse → (Glu)Human replacement. At the nucleotide level, high-GC orthologs have undergone a large excess of (A/T)Mouse → (G/C)Human substitutions over (G/C)Mouse → (A/T)Human at each codon position, whereas for low-GC orthologs, the reverse is true.
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