Implications of human genome structural heterogeneity: functionally related genes tend to reside in organizationally similar genomic regions

Abstract

BackgroundIn an earlier study, we hypothesized that genomic segments with different sequence organization patterns (OPs) might display functional specificity despite their similar GC content. Here we tested this hypothesis by dividing the human genome into 100 kb segments, classifying these segments into five compositional groups according to GC content, and then characterizing each segment within the five groups by oligonucleotide counting (k-mer analysis; also referred to as compositional spectrum analysis, or CSA), to examine the distribution of sequence OPs in the segments. We performed the CSA on the entire DNA, i.e., its coding and non-coding parts the latter being much more abundant in the genome than the former.ResultsWe identified 38 OP-type clusters of segments that differ in their compositional spectrum (CS) organization. Many of the segments that shared the same OP type were enriched with genes related to the same biological processes (developmental, signaling, etc.), components of biochemical complexes, or organelles. Thirteen OP-type clusters showed significant enrichment in genes connected to specific gene-ontology terms. Some of these clusters seemed to reflect certain events during periods of horizontal gene transfer and genome expansion, and subsequent evolution of genomic regions requiring coordinated regulation.ConclusionsThere may be a tendency for genes that are involved in the same biological process, complex or organelle to use the same OP, even at a distance of ~ 100 kb from the genes. Although the intergenic DNA is non-coding, the general pattern of sequence organization (e.g., reflected in over-represented oligonucleotide “words”) may be important and were protected, to some extent, in the course of evolution.

Maximum Likelihood Estimation of the Evolutionary Distance of Complete Genomes of Mitochondrial DNA between Human and 16 Animals

“…There was a total of 4091 positions in the final dataset. Similar to the previous results, the pig got the highest contrast distance against the others [61].…”

Understanding genome composition of eusocial hymenopteran insects

“…These studies have yielded congruent results with several studies on other animals that show GC-poor and GC-rich regions have shown distinct functional properties (Jabbari, Chakraborty, & Wiehe, 2019;Paz, Frenkel, Snir, Kirzhner, & Korol, 2014). Although these studies have shed light on the relevance of GC content, very limited work has been done…”

Physicochemical Foundations of Life that Direct Evolution: Chance and Natural Selection are not Evolutionary Driving Forces

“…In conclusion, composition bias determines, on the one hand, the location of genes in the 3D nuclear space and, on the other hand, gene product functions. Accordingly, genes contributing to the same cellular processes are in linear proximity in prokaryotes, and in 3D proximity in the nuclear space in eukaryotes [154][155][156]254,[260][261][262]. Composition biases driving physicochemical properties of polymers, therefore, establish a straightforward link between production and function of gene products.…”