Terminology Recap: Genome / Chromosome / Nucleosome / Chromatin / Chromatid / DNA / Double Strands / Coordinates System / Upstream & Downstream / TSS Distance

1. Genome

Genome is the genetic material of an organism. It consists of DNA, or RNA in RNA viruses. 具体说来，下列元素都属于 genome：

• DNA
  • protein-coding genes
  • pseudogenes
  • transposon (TE - transposoble element)
  • DNA elements that can ‘jump’ to a new genomic location
• RNA
  • rRNA (ribosomal RNA)
  • tRNA (transfer RNA)
  • short non-coding RNA
    • miRNA (microRNA)
      • MicroRNAs usually induce gene silencing by binding to target sites found within the 3’UTR of the targeted mRNA. This interaction prevents protein production by suppressing protein synthesis and/or by initiating mRNA degradation.
      • MicroRNAs are partially complementary to one or more messenger RNA (mRNA) molecules, and their main function is to downregulate gene expression in a variety of manners, including translational repression, mRNA cleavage, and deadenylation.
    • siRNA (short interfering RNA, double-stranded)
      • may come from outside the cell (e.g. virus); endo-siRNA also discovered, transcribed from cell’s own DNA
      • the most commonly used RNA interference (RNAi) tool for inducing short-term silencing of protein coding genes
      • siRNA is a synthetic RNA duplex designed to specifically target a particular mRNA for degradation.
    • 参考：
      • siRNA Applications
      • Learn the Distinction Between siRNA and miRNA
  • lncRNA (long non-coding RNA)
    • $\ge$ 2000 nt
    • variety of functions

DNA/RNA 其实是 molecule 的名称，所以 genome 和 DNA/RNA 的关系大致相当于 “一坨炭” 和 “碳分子” 的关系

2. Chromosome / Chromatin / Nucleosome / Chromatid / DNA / Double Strands

• DNA 是大分子名，Double Strand (or Double Helix) 是它的物理结构，它由下面两类元素构成：
  • Nucleotide ([‘nju:klɪətaɪd], 核苷酸)，包括：
    • Adenine ([‘ædənɪn], 腺嘌吟)
    • Cytosine ([‘saɪtəʊsi:n], 胞嘧啶)
    • Guanine ([‘gwɑ:ni:n], 鸟嘌呤)
    • Thymine ([‘θaɪmi:n], 胸腺嘧啶)
  • Sugar-Phosphate Backbone
• DNA + histone 的 complex 整体叫做 chromotin
  • The basic repeating structural (and functional) unit of chromatin is the nucleosome, which contains 8 histone proteins and about 146 bp of DNA
  • 参 DNA Packaging: Nucleosomes and Chromatin
• cell 在不分裂的情况下，可以认为：一条 further condensed chromatin 就是一条 chromosome
  • chromosome 按功能分类可以分为 allosome ([‘ælʊsəʊm], 性染色体) / autosome ([‘ɔ:təsəʊm], 常染色体)
  • 人体的 autosome 是按长度从长到短编号的，最长的是 1 号，最短的是 22 号
  • 类似 chr18 这样的都是 1 条 chromosome 的名字，我们说人体每个细胞都有 a pair of chr18’s
    • pair up 的两条 chromosomes 称为 homologous chromosomes (或 homologs for short), 原义是指 identical to one another in shape and size，但明显 XY 不能算
    • “identical in shape and size” 明显不意味着 “identical in sequence”
    • We can specify maternal chr18 and paternal chr18 to indicate from which parent it is inherited.
• cell 在分裂的情况下 (具体在 Cell Cycle 的 S phase)，一条 chromatin 会分裂成两条 chromatids
  • Every chromatid has a short p-arm (“p” for “petit”) and a long q-arm (“q” for “queue”)
  • Every 2 chromatids are connected by a centromere.
  • 我们在研究单条 chromosome 的时候仍然会使用 p-arm、q-arm 和 centromere 来细分单条 chromosome 的结构
  • 注意： 我们经常看到的 chromosome 的图片都是一个 X-shaped with 4 arms 的结构，这其实是分裂中的两条 chromatids，注意这并不是 chromosome 的正常形态，人体内并不是有 23 对这样的 X-shaped chromosomes (我 TM 被这个图片骗惨了！)
    • 更多讨论见 Quora: Why a chromosome is represented as X shaped with four chromatids while by definition it has two chromatids?

数量关系：

• Every human cell has 23 pairs == 46 chromosomes
• 1 chromosome == 2 strands
• So every human cell has 92 strands

3. Coordinates Systems / Upstream & Downstream / TSS Distance

我们前面一路从 DNA zoom in 到 chromosome，现在进一步 zoom in 到 strand：

• chromStart and chromEnd are columns from table snp142 of database hg19 in UCSC Genome Browser
• txStart and txEnd are columns from table ensGene of database hg19 in UCSC Genome Browser
• 0-based coordinate system is used here

3.1 Coordinates Systems

参考 Tutorial: Cheat Sheet For One-Based Vs Zero-Based Coordinate Systems:

• 0-based：
  • UCSC Genome Browser
  • BED, BAM formats
• 1-based
  • HGMD
  • Ensembl
  • GFF, SAM, VCF formats
• 转换规则：
  • $chromStart_{0} = chromStart_{1} - 1$
  • $chromEnd_{0} = chromEnd_{1}$

3.2 Upstream & Downstream

• Upstream: direction $\Rightarrow 5’$
• Downstream: direction $\Rightarrow 3’$
  • 参考 Upstream and downstream (DNA)

3.3 Directions of Strands

• 参考 Question: Forward And Reverse Strand Conventions
• This designation of (+)/(-) strand is arbitrary.
  • Once fixed, the (+) strand determines the direction of coordinate axis;
  • then (-) strand goes reversely.
• A gene $g$ can be on the (+) strand or (-) strand:
  • The strand that $g$ is on is called $g$’s coding strand (a.k.a. its sense strand).
  • The other strand is called $g$’s template strand (a.k.a. its antisense strand)
  • If $\operatorname{strand}(g) =$ (+) $\Rightarrow \operatorname{TSS}(g) = g.txStart$
  • If $\operatorname{strand}(g) =$ (-) $\Rightarrow \operatorname{TSS}(g) = g.txEnd$
    • N.B. $g.txStart < g.txEnd$ always holds

3.4 TSS Distance

• TSS: Transcription Start Site`
  • TSS distance: actually means “distance to TSS”
• Given a SNP $s$ and a gene $g$:
  • If $\operatorname{strand}(g) =$ (+) $\Rightarrow \operatorname{TSS-dist}(s,g) = s.chromStart - g.txStart$;
  • If $\operatorname{strand}(g) =$ (-) $\Rightarrow \operatorname{TSS-dist}(s,g) = g.txEnd - s.chromStart$.
  • In other words, suppose:
    • $\operatorname{strand}(g) = \begin{cases} 1 & \text{ g is on (+) strand} \newline -1 & \text{otherwise} \end{cases}$
    • $\operatorname{TSS}(g) = \begin{cases} g.txStart & \text{ g is on (+) strand} \newline g.txEnd & \text{otherwise} \end{cases}$
      • $\Rightarrow \operatorname{TSS-dist}(s,g) = (s.chromStart - \operatorname{TSS}(g)) \times \operatorname{strand}(g)$
  • If $s$ is in the upstream of $g$, $\operatorname{TSS-dist}(s,g) < 0$, whichever strand $g$ is on
  • If $s$ is in the downstream of $g$, $\operatorname{TSS-dist}(s,g) > 0$, whichever strand $g$ is on